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Jeyaraman N, Jeyaraman M, Dhanpal P, Ramasubramanian S, Nallakumarasamy A, Muthu S, Santos GS, da Fonseca LF, Lana JF. Integrative review of the gut microbiome’s role in pain management for orthopaedic conditions. World J Exp Med 2025; 15:102969. [DOI: 10.5493/wjem.v15.i2.102969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Revised: 03/03/2025] [Accepted: 04/01/2025] [Indexed: 04/16/2025] Open
Abstract
The gut microbiome, a complex ecosystem of microorganisms, has a significant role in modulating pain, particularly within orthopaedic conditions. Its impact on immune and neurological functions is underscored by the gut-brain axis, which influences inflammation, pain perception, and systemic immune responses. This integrative review examines current research on how gut dysbiosis is associated with various pain pathways, notably nociceptive and neuroinflammatory mechanisms linked to central sensitization. We highlight advancements in meta-omics technologies, such as metagenomics and metaproteomics, which deepen our understanding of microbiome-host interactions and their implications in pain. Recent studies emphasize that gut-derived short-chain fatty acids and microbial metabolites play roles in modulating neuroinflammation and nociception, contributing to pain management. Probiotics, prebiotics, synbiotics, and faecal microbiome transplants are explored as potential therapeutic strategies to alleviate pain through gut microbiome modulation, offering an adjunct or alternative to opioids. However, variability in individual microbiomes poses challenges to standardizing these treatments, necessitating further rigorous clinical trials. A multidisciplinary approach combining microbiology, immunology, neurology, and orthopaedics is essential to develop innovative, personalized pain management strategies rooted in gut health, with potential to transform orthopaedic pain care.
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Affiliation(s)
- Naveen Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
| | - Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, São Paulo, Brazil
| | - Priya Dhanpal
- Department of Orthopaedics, Government Medical College, Omandurar Government Estate, Chennai 600002, Tamil Nadu, India
| | - Swaminathan Ramasubramanian
- Department of Orthopaedics, Government Medical College, Omandurar Government Estate, Chennai 600002, Tamil Nadu, India
| | - Arulkumar Nallakumarasamy
- Department of Orthopaedics, Jawaharlal Institute of Postgraduate Medical Education and Research–Karaikal, Puducherry 609602, India
| | - Sathish Muthu
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Central Research Laboratory, Meenakshi Medical College Hospital and Research Institute, Meenakshi Academy of Higher Education and Research, Chennai 631552, Tamil Nadu, India
| | - Gabriel Silva Santos
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, São Paulo, Brazil
| | - Lucas Furtado da Fonseca
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, São Paulo, Brazil
| | - José Fábio Lana
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, São Paulo, Brazil
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Ray D, Bose P, Mukherjee S, Roy S, Kaity S. Recent drug delivery systems targeting the gut-brain-microbiome axis for the management of chronic diseases. Int J Pharm 2025; 680:125776. [PMID: 40425058 DOI: 10.1016/j.ijpharm.2025.125776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 05/14/2025] [Accepted: 05/24/2025] [Indexed: 05/29/2025]
Abstract
In recent years, the study of microorganisms and the brain has become increasingly connected. The gut-brain-microbiome axis (GBMA), a bi-directional communication system, is the key part of how the body's bacteria and the brain interact. This system can influence the brain and behaviour. Changes in this relationship have been linked to various mental and physical health conditions. The immune system, tryptophan metabolism, the vagus nerve, and the enteric nervous system all facilitate connections between the gut and brain. Microbes produce Peptidoglycans, branched-chain amino acids, and short-chain fatty acids, which are involved in this communication. Studies suggest the gut microbiome may be involved in conditions like autism, anxiety, obesity, schizophrenia, Parkinson's disease, and Alzheimer's disease. Researchers are exploring the gut-brain connection to cure a variety of disorders, such as neurological disorders, cancers, metabolic problems, and liver diseases. Developing novel drug delivery systems is a key focus in GBMA for therapeutic targeting at various disease pathways. Notable platforms attracting significant interest include silica nanoparticle-based delivery systems for probiotic spores, composite hydrogels formulated from protein isolates and citrus pectin, and biomimetic nanosystems designed for targeted therapeutic delivery. This review summarizes different methods of delivering drugs and using dietary interventions to target the GBMA and treat these conditions in a less invasive way. By understanding how the gut and brain communicate, scientists aim to develop new and more effective therapies for these complex chronic diseases.
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Affiliation(s)
- Debjani Ray
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal, India
| | - Piyas Bose
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal, India
| | - Saptarshi Mukherjee
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal, India
| | - Subhadeep Roy
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal, India
| | - Santanu Kaity
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal, India.
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Bhattacharya A, Shepherd C, El-Assaad F, Mather KA. Bacteria in the brain: do they have a role in the pathogenesis of Alzheimer's disease? Curr Opin Psychiatry 2025; 38:252-257. [PMID: 40013501 PMCID: PMC11957443 DOI: 10.1097/yco.0000000000000989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/28/2025]
Abstract
PURPOSE OF REVIEW Worldwide efforts continue to unravel the complex pathological pathways that lead to Alzheimer's disease. The gut-brain-microbiome axis, a communication pathway between the gut, brain and microorganisms, is emerging as a potential mechanism involved in Alzheimer's disease pathogenesis. While the gut microbiome's role in Alzheimer's disease has gained significant attention, the brain microbiome remains relatively unexplored. This review summarizes the latest research on the brain microbiome in Alzheimer's disease. RECENT FINDINGS In the past 4 years, four out of five studies have found bacteria, such as Streptococcus pneumoniae , in postmortem samples of both control and Alzheimer's disease brains, supporting the idea that the brain is not a sterile environment. Two studies report the overabundance of several bacterial phyla, including Proteobacteria and Actinomycetes, in postmortem Alzheimer's disease brains versus controls. One study reported the presence of Borrelia burgdorferi in a subset of Alzheimer's disease cases compared to controls. SUMMARY Limitations and challenges persist in studying the brain microbiome, including the lack of standardized assays and data analysis methods, small sample sizes, and inconsistent use of controls for environmental microbial contamination during sample processing. Well designed studies that employ reproducible and rigorous methods are required to elucidate whether microbes are involved in the pathogenesis of Alzheimer's disease.
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Affiliation(s)
- Arnav Bhattacharya
- Centre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington
| | - Claire Shepherd
- Sydney Brain Bank, Neuroscience Research Australia (NeuRA), Randwick
- Department of Pathology, School of Biomedical Sciences, University of New South Wales, Kensington
| | - Fatima El-Assaad
- Microbiome Research Centre, Centre, St. George and Sutherland Clinical Campuses, UNSW Sydney, New South Wales, Australia
| | - Karen A. Mather
- Centre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington
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Mosquera FEC, de la Rosa Caldas M, Naranjo Rojas A, Perlaza CL, Liscano Y. Probiotic, Prebiotic, and Synbiotic Supplementation for the Prevention and Treatment of Acute Otitis Media: A Systematic Review and Meta-Analysis. CHILDREN (BASEL, SWITZERLAND) 2025; 12:591. [PMID: 40426770 DOI: 10.3390/children12050591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/26/2025] [Revised: 04/23/2025] [Accepted: 04/29/2025] [Indexed: 05/29/2025]
Abstract
BACKGROUND AND AIM Probiotics, prebiotics, and synbiotics have been documented to modulate the microbiota, enhance immunity, and reduce antibiotic resistance, making them a promising alternative in the management of acute otitis media (AOM). Accordingly, the aim of this study was to determine their effectiveness in the prevention and treatment of AOM in patients. METHODS A systematic review and meta-analysis of randomized controlled trials published between 2000 and 2024 was conducted using Science Direct, PubMed, LILACS, SCOPUS, Web of Science, and Cochrane Clinical Trials, following PRISMA guidelines. The methodological quality was evaluated using the Jadad scale, and the meta-analysis was performed with RevMan 5.4® and Jamovi 2.3.28®. RESULTS A total of 16 trials with 4034 patients were included. The meta-analysis showed that the intervention did not affect the time to AOM presentation (MD: -7.98; 95% CI: -19.74 to 3.78; p = 0.18), the recurrence of the disease (RR: 0.99; 95% CI: 0.74-1.33; p = 0.96), or the requirement for antibiotics (RR: 1.31; 95% CI: 0.92 to 1.84; p = 0.13); however, it was associated with a reduced probability of developing AOM (RR: 0.80; 95% CI: 0.66 to 0.96; p = 0.02). Subgroup analysis suggests that the effect of probiotic supplementation on AOM incidence is influenced by treatment duration, patient age, and the number of probiotic strains in the product. CONCLUSIONS Supplementation with probiotics, prebiotics, or synbiotics is associated with a significant reduction in the incidence of AOM in children, although no significant impact was observed on other key clinical parameters. These interventions may be considered as a complementary strategy to conventional treatments; however, further high-quality, standardized trials are needed to confirm these findings and to define optimal protocols.
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Affiliation(s)
- Freiser Eceomo Cruz Mosquera
- Grupo de Investigación en Salud Integral (GISI), Department of Health Sciences Faculty, Universidad Santiago de Cali, Cali 760035, Colombia
| | - Mayerli de la Rosa Caldas
- Grupo de Investigación en Salud Integral (GISI), Department of Health Sciences Faculty, Universidad Santiago de Cali, Cali 760035, Colombia
| | - Anisbed Naranjo Rojas
- Grupo de Investigación en Salud Integral (GISI), Department of Health Sciences Faculty, Universidad Santiago de Cali, Cali 760035, Colombia
| | - Claudia Lorena Perlaza
- Grupo de Investigación en Salud Integral (GISI), Department of Health Sciences Faculty, Universidad Santiago de Cali, Cali 760035, Colombia
| | - Yamil Liscano
- Grupo de Investigación en Salud Integral (GISI), Department of Health Sciences Faculty, Universidad Santiago de Cali, Cali 760035, Colombia
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Iwasaki S, Také A, Uojima H, Horio K, Sakaguchi Y, Gotoh K, Satoh T, Hidaka H, Tanaka Y, Hayashi S, Kusano C. Quantification of Streptococcus salivarius using the digital polymerase chain reaction as a liver fibrosis marker. World J Hepatol 2025; 17:102027. [PMID: 40308822 PMCID: PMC12038421 DOI: 10.4254/wjh.v17.i4.102027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Revised: 02/21/2025] [Accepted: 04/09/2025] [Indexed: 04/25/2025] Open
Abstract
BACKGROUND The Streptococcus salivarius (S. salivarius) group, which produces the enzyme urease has been identified as a potential contributor to ammonia production in the gut. Researchers have reported that patients with minimal HE had an increased abundance of the S. salivarius group, which is a specific change in the gut microbiota that distinguishes them from healthy individuals. The correlation between the aggregation of specific bacterial species and fibrosis progression in chronic liver disease (CLD) is yet to be fully elucidated. AIM To quantify S. salivarius using digital PCR (dPCR) as a liver fibrosis marker of CLD. METHODS This study retrospectively analysed 52 patients with CLD. To quantify S. salivarius in patients with CLD using dPCR, we evaluated the specificity and sensitivity of S. salivarius bacterial load using dPCR for a type strain. Next, we evaluated the clinical usefulness of dPCR for S. salivarius load quantification for detecting liver fibrosis in patients with CLD. The liver fibrosis stage was categorized into mild and advanced fibrosis based on pathological findings. RESULTS The dPCR assay revealed that S. salivarius was highly positive for the tnpA gene. The lower limit of quantification for dPCR using the tnpA gene with a 1 μL template comprising 1.28 × 102 CFU/mL was 4.3 copies. After considering the detection range in dPCR, we adjusted the extracted DNA concentration to 5.0 × 10-4 ng/μL from 200 mg stool samples. The median bacterial loads of S. salivarius in stool sample from patients with mild and advanced fibrosis were 1.9 and 7.4 copies/μL, respectively. The quantification of S. salivarius load was observed more frequently in patients with advanced fibrosis than in those with mild fibrosis (P = 0.032). CONCLUSION Quantifying of S. salivarius load using digital PCR is a useful biomarker for liver fibrosis in patients with CLD.
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Affiliation(s)
- Shuichiro Iwasaki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara 252-0375, Kanagawa, Japan
| | - Akira Také
- Department of Microbiology, Kitasato University School of Medicine, Sagamihara 252-0373, Kanagawa, Japan
| | - Haruki Uojima
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara 252-0375, Kanagawa, Japan
- Department of Genome Medical Sciences Project, Research Institute, National Center for Global Health and Medicine, Ichikawa 272-8516, Chiba, Japan.
| | - Kazue Horio
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara 252-0375, Kanagawa, Japan
| | - Yoshihiko Sakaguchi
- Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8055, Japan
| | - Kazuyoshi Gotoh
- Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| | - Takashi Satoh
- Division of Hematology, Kitasato University School of Allied Health Sciences, Sagamihara 252-0373, Kanagawa, Japan
| | - Hisashi Hidaka
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara 252-0375, Kanagawa, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Kumamoto University Hospital, Kumamoto 860-8556, Japan
| | - Shunji Hayashi
- Department of Microbiology, Kitasato University School of Medicine, Sagamihara 252-0373, Kanagawa, Japan
| | - Chika Kusano
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara 252-0375, Kanagawa, Japan
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Corbin KD, Igudesman D, Smith SR, Zengler K, Krajmalnik-Brown R. Targeting the Gut Microbiota's Role in Host Energy Absorption With Precision Nutrition Interventions for the Prevention and Treatment of Obesity. Nutr Rev 2025:nuaf046. [PMID: 40233201 DOI: 10.1093/nutrit/nuaf046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/17/2025] Open
Abstract
The field of precision nutrition aims to develop dietary approaches based on individual biological factors such as genomics or the gut microbiota. The gut microbiota, which is the highly individualized and complex community of microbes residing in the colon, is a key contributor to human physiology. Although gut microbes play multiple roles in the metabolism of nutrients, their role in modulating the absorption of dietary energy from foods that escape digestion in the small intestine has the potential to variably affect energy balance and, thus, body weight. The fate of this energy, and its subsequent impact on body weight, is well described in rodents and is emerging in humans. This narrative review is focused on recent clinical evidence of the role of the gut microbiota in human energy balance, specifically its impact on energy available to the human host. Despite recent progress, remaining gaps in knowledge present opportunities for developing and implementing strategies to understand causal microbial mechanisms related to energy balance. We propose that implementing rigorous microbiota-focused measurements in the context of innovative clinical trial designs will elucidate integrated diet-host-gut microbiota mechanisms. These mechanisms are primed to be targets for precision nutrition interventions to optimize energy balance to achieve desired weight outcomes. Given the magnitude and impact of the obesity epidemic, implementing these interventions within comprehensive weight management paradigms has the potential to be of public health significance.
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Affiliation(s)
- Karen D Corbin
- AdventHealth Translational Research Institute, Orlando, FL 32804, United States
| | - Daria Igudesman
- AdventHealth Translational Research Institute, Orlando, FL 32804, United States
| | - Steven R Smith
- AdventHealth Translational Research Institute, Orlando, FL 32804, United States
| | - Karsten Zengler
- Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, United States
- Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, United States
- Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, United States
| | - Rosa Krajmalnik-Brown
- Biodesign Center for Health through Microbiomes, Arizona State University, Tempe, AZ 85281, United States
- School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ 85281, United States
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Gebrehiwot NT, Liu Y, Li J, Liu HM. Molecular Alterations in Gastric Intestinal Metaplasia Shed Light on Alteration of Methionine Metabolism: Insight into New Diagnostic and Treatment Approaches. Biomedicines 2025; 13:964. [PMID: 40299656 PMCID: PMC12025106 DOI: 10.3390/biomedicines13040964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2025] [Revised: 04/03/2025] [Accepted: 04/08/2025] [Indexed: 05/01/2025] Open
Abstract
Gastric intestinal metaplasia (GIM) is a precancerous lesion and the key risk factor in the development of gastric cancer (GC), but early detection and treatment remain challenging. The traditional endoscopic diagnosis of metaplastic lesions is complicated by an increased rate of inappropriateness and false negativity. Although early interventions with H. pylori eradication, as well as endoscopic therapy results, were promising, there is still a significant unmet need to control GIM progression and recurrences. Molecular alterations, such as an increased DNA methylation index, have been identified as a crucial factor in the downregulation of tumor suppressor genes, such as the caudal-type homeobox (CDX2) gene, which regulates epithelial cell proliferation and GIM progression and is associated with treatment failure. CDX2 is downregulated by promoter hypermethylation in the colonic-type epithelium, in which the methylation was correlated with reduced intake of dietary folate sources. Tumor cells alter to dietary methionine sources in the biosynthesis of S-Adenosylmethionine, a universal methyl donor for transmethylation, under the conditions of limited folate and B12 availability. The gut microbiota also exhibited a shift in microbial composition, which could influence the host's dietary methionine metabolism. Meanwhile, activated oncogenic signaling via the PI3K/Akt/mTORC1/c-MYC pathway could promotes rewiring dietary methionine and cellular proliferation. Tumor methionine dependence is a metabolic phenotype that could be helpful in predictive screening of tumorigenesis and as a target for preventive therapy to enhance precision oncology. This review aimed to discuss the molecular alterations in GIM to shed light on the alteration of methionine metabolism, with insight into new diagnostic and treatment approaches and future research directions.
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Affiliation(s)
- Nigatu Tadesse Gebrehiwot
- School of Pharmaceutical Sciences, Institute of Drug Discovery and Development, Zhengzhou University, Zhengzhou 450001, China;
- Key Laboratory of Advanced Drug Preparation Technologies, Zhengzhou University, Ministry of Education, Zhengzhou 450001, China
| | - Ying Liu
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China;
| | - Juan Li
- School of Pharmaceutical Sciences, Institute of Drug Discovery and Development, Zhengzhou University, Zhengzhou 450001, China;
- Key Laboratory of Advanced Drug Preparation Technologies, Zhengzhou University, Ministry of Education, Zhengzhou 450001, China
| | - Hong-Min Liu
- School of Pharmaceutical Sciences, Institute of Drug Discovery and Development, Zhengzhou University, Zhengzhou 450001, China;
- Key Laboratory of Advanced Drug Preparation Technologies, Zhengzhou University, Ministry of Education, Zhengzhou 450001, China
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Pei X, Liu L, Han Y. Advances in human microbiome and prostate cancer research. Front Immunol 2025; 16:1576679. [PMID: 40297591 PMCID: PMC12034659 DOI: 10.3389/fimmu.2025.1576679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Accepted: 03/26/2025] [Indexed: 04/30/2025] Open
Abstract
Prostate cancer (PCa) is the second most common malignant tumor in men worldwide, and its metastatic and heterogeneous nature makes it significantly more difficult to treat. Recent studies have revealed the critical role of microbiota in PCa occurrence, progression, and treatment. Accumulating evidence from 16S rRNA and metagenomic sequencing suggests the presence of specific microbiota in prostate tissues and macrogenomics techniques: cancerous tissues are enriched with pro-inflammatory genera (e.g., Fusobacterium, Propionibacterium acnes), whereas commensal bacteria (e.g., Pseudomonas) are more common in paracancerous tissues. The microbiota drive tumor progression through activation of the NF-κB/STAT3 pathway to induce chronic inflammation, modulation of the immune microenvironment (e.g., Treg/Th17 imbalance and M2-type macrophage polarization), and metabolite (e.g., LPS, short-chain fatty acids)-mediated hormonal and epigenetic regulation. In terms of clinical translation, urinary microbiota characterization combined with metabolomics analysis may enhance diagnostic specificity, while gut flora modulation (e.g., probiotic interventions or fecal transplants) may improve resistance to androgen deprivation therapy. Current challenges include sequencing accuracy of low-biomass samples, limitations of causal mechanism validation models, and large cohort heterogeneity. In the future, it will be necessary to integrate multi-omics technologies to explore the bidirectional regulation of the "gut-prostate axis" and develop personalized therapeutic strategies targeting microorganisms. In this paper, we systematically review the interactions between microbiota and PCa and their clinical potentials to provide a theoretical basis for precision diagnosis and treatment.
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Affiliation(s)
- Xin Pei
- Department of Urology, China-Japan Union Hospital, Jilin University, Changchun, China
| | - Lei Liu
- Department of Endocrine, China-Japan Union Hospital, Jilin University, Changchun, China
| | - Yuping Han
- Department of Urology, China-Japan Union Hospital, Jilin University, Changchun, China
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Yang SY, Han SM, Lee JY, Kim KS, Lee JE, Lee DW. Advancing Gut Microbiome Research: The Shift from Metagenomics to Multi-Omics and Future Perspectives. J Microbiol Biotechnol 2025; 35:e2412001. [PMID: 40223273 PMCID: PMC12010094 DOI: 10.4014/jmb.2412.12001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 02/14/2025] [Accepted: 02/24/2025] [Indexed: 04/15/2025]
Abstract
The gut microbiome, a dynamic and integral component of human health, has co-evolved with its host, playing essential roles in metabolism, immunity, and disease prevention. Traditional microbiome studies, primarily focused on microbial composition, have provided limited insights into the functional and mechanistic interactions between microbiota and their host. The advent of multi-omics technologies has transformed microbiome research by integrating genomics, transcriptomics, proteomics, and metabolomics, offering a comprehensive, systems-level understanding of microbial ecology and host-microbiome interactions. These advances have propelled innovations in personalized medicine, enabling more precise diagnostics and targeted therapeutic strategies. This review highlights recent breakthroughs in microbiome research, demonstrating how these approaches have elucidated microbial functions and their implications for health and disease. Additionally, it underscores the necessity of standardizing multi-omics methodologies, conducting large-scale cohort studies, and developing novel platforms for mechanistic studies, which are critical steps toward translating microbiome research into clinical applications and advancing precision medicine.
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Affiliation(s)
- So-Yeon Yang
- Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
| | - Seung Min Han
- Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
| | - Ji-Young Lee
- Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
| | - Kyoung Su Kim
- Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
| | - Jae-Eun Lee
- Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
| | - Dong-Woo Lee
- Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
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Fang X, Wang Y, Wei H, Huang Y. Precision Microbiome: A New Era of Targeted Therapy with Core Probiotics. RESEARCH (WASHINGTON, D.C.) 2025; 8:0658. [PMID: 40143943 PMCID: PMC11938712 DOI: 10.34133/research.0658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2025] [Accepted: 03/11/2025] [Indexed: 03/28/2025]
Affiliation(s)
- Xiuyu Fang
- College of Animal Science and Technology,
Northeast Agricultural University, Harbin 150030, China
| | - Yuhao Wang
- Zhejiang Provincial Key Laboratory of Pancreatic Disease of The First Affiliated Hospital, Institute of Translational Medicine,
Zhejiang University School of Medicine, Hangzhou 310029, Zhejiang, China
| | - Hong Wei
- Yu-Yue Pathology Scientific Research Center, Jinfeng Laboratory, Chongqing 401329, China
| | - Yuan Huang
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases,
Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
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11
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Ma W, Han Z, Liu X, Cui W, Zhen D, Zhou X, Song Y, Jiang S. Distinct Effects of Lactiplantibacillus plantarum HNU082 on Microbial Single-Nucleotide Variants in Large Intestine and Small Intestine. Microorganisms 2025; 13:731. [PMID: 40284568 PMCID: PMC12029867 DOI: 10.3390/microorganisms13040731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Accepted: 03/18/2025] [Indexed: 04/29/2025] Open
Abstract
The intestinal tract extends several times the length of bodies, with varying environmental conditions across different segments (small intestinal and large intestinal), thereby harboring distinct gut microbiota. Most studies focused on the quantitative responses of gut microbiota upon probiotics entering the gut, without an in-depth analysis of how the genetic change in local gut microbiota. Therefore, in this experiment, C57BL/6J male mice were once administered Lactiplantibacillus plantarum HNU082 (Lp082). Then, the mice were euthanized on the 1st, 3rd, and 7th days after gavage, and the contents of the small and large intestines of the mice were scraped for metagenomic analysis. Based on the characterization of large intestine and small intestine bacteria, changes in the diversity and abundance of single-nucleotide variants (SNVs) of microbiota were analyzed. There were observable distinct responses at the genetic level. A significant number of SNVs were identified in Ligilactobacillus murinus in the large intestine. These SNVs may impact the utilization of carbohydrates in L. murinus. Ingested probiotics traversed the entire gut and interacted with the indigenous microbiota, driving the evolution of the indigenous gut microbiota in the different intestinal segments, thereby influencing microbial growth and metabolism. This study investigates the role of probiotics in the evolution of gut microbiota. It offers new probiotic insights and a basis for targeted interventions.
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Affiliation(s)
| | | | | | | | | | | | | | - Shuaiming Jiang
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, School of Food Science and Engineering, Hainan University, Haikou 570228, China; (W.M.); (Z.H.); (X.L.); (W.C.); (D.Z.); (X.Z.); (Y.S.)
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12
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Kelliher JM, Rodriguez FE, Johnson LYD, Roux S, Smith M, Clum A, Lynch W, Bias CH, Finks SS, Keenum I, Kiledal EA, Lin HA, Longley R, McDonald R, Pitot TM, Rodríguez-Ramos J, Shen J, Sprockett DD, Swift J, Yadav A, Eloe-Fadrosh EA. Quantifying the impact of workshops promoting microbiome data standards and data stewardship. Sci Rep 2025; 15:9887. [PMID: 40121238 PMCID: PMC11929805 DOI: 10.1038/s41598-025-89991-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 02/10/2025] [Indexed: 03/25/2025] Open
Abstract
The field of microbiome research continues to grow at a rapid pace, with multi-omics approaches becoming widely used to interrogate diverse microbiome samples. However, due to lagging awareness and implementation of standards and data stewardship, many datasets are produced that are not comparable, reproducible, or reusable. In 2021, the National Microbiome Data Collaborative launched its Ambassador Program, which utilizes a community-learning model to annually train a cohort of early-career researchers in microbiome data stewardship best practices. These Ambassadors then host workshops and other events to communicate these themes to their respective microbiome research communities. To quantify the impact of this learning model for promoting awareness of and experience with microbiome data, we conducted a survey of workshop participants from events hosted by the 2023 Ambassador cohort. The 2023 cohort of 13 National Microbiome Data Collaborative Ambassadors collectively hosted 21 events, reaching over 550 researchers. The Ambassadors distributed an anonymous post-workshop survey to their event participants to quantify the effectiveness of the training materials, the workshop format, and the thematic content. From the 21 events, survey results were successfully collected for 15 of those events from a total of 122 researchers. Overall, 122 participants working with a range of microbiome types and from a variety of institutions responded to the survey and reported overwhelmingly positive experiences with the workshop content and materials, with 98% of respondents reporting that they gained knowledge from the event. Participants across the events also reported an increase in their post-workshop understanding of metadata standards, principles for microbiome data management and reporting, and the importance of standardization in microbiome data processing. Participants also expressed a willingness to apply what they learned about microbiome data stewardship to their own research. The results of this study demonstrate the effectiveness of hands-on workshops and community-learning for communicating data stewardship best practices to microbiome researchers. The lessons learned and details about the implementation of this cohort-based learning model contained herein are intended to assist other groups in their efforts to create or improve similar learning strategies.
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Affiliation(s)
- Julia M Kelliher
- Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
| | | | - Leah Y D Johnson
- Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA
| | - Simon Roux
- Lawrence Berkeley National Laboratory, Berkeley, CA, USA
| | - Montana Smith
- Pacific Northwest National Laboratory, Richland, WA, USA
| | - Alicia Clum
- Lawrence Berkeley National Laboratory, Berkeley, CA, USA
| | - Wendi Lynch
- Lawrence Berkeley National Laboratory, Berkeley, CA, USA
| | - Candace Hope Bias
- U.S. Food and Drug Administration, College Park, MD, USA
- Oak Ridge Institute for Science and Education, Oak Ridge, TN, USA
| | - Sarai S Finks
- Department of Biology, The Pennsylvania State University, University Park, PA, USA
| | - Ishi Keenum
- Michigan Technological University, Houghton, MI, USA
| | - E Anders Kiledal
- Department of Earth and Environmental Sciences, University of Michigan, Ann Arbor, MI, USA
| | - Heng-An Lin
- Texas A&M University, College Station, TX, USA
| | - Reid Longley
- Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA
| | - Ryan McDonald
- U.S. Food and Drug Administration, College Park, MD, USA
| | - Thomas M Pitot
- Department of Biochemistry, Microbiology and Bioinformatics, Université Laval, Québec, QC, Canada
| | | | | | - Daniel D Sprockett
- Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, NY, USA
| | - Joel Swift
- Kansas Biological Survey & Center for Ecological Research, University of Kansas, Lawrence, KS, USA
| | - Archana Yadav
- Lawrence Berkeley National Laboratory, Berkeley, CA, USA
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13
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France MT, Chaudry I, Rutt L, Quain M, Shirtliff B, McComb E, Maros A, Alizadeh M, Hussain FA, Elovitz MA, Relman DA, Rahman A, Brotman RM, Price J, Kassaro M, Holm JB, Ma B, Ravel J. VIRGO2: Unveiling the Functional and Ecological Complexity of the Vaginal Microbiome with an Enhanced Non-Redundant Gene Catalog. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.03.04.641479. [PMID: 40093185 PMCID: PMC11908257 DOI: 10.1101/2025.03.04.641479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/19/2025]
Abstract
Despite the importance of the cervicovaginal microbiome, the mechanisms that govern its composition and drive its impact on host physiology remain poorly understood. This study expands our understanding of the function and ecology of the vaginal microbiome using VIRGO2, an enhanced non-redundant gene catalog comprising over 1.7 million well-annotated genes from body-site specific microbes and viruses. Analyses using VIRGO2 revealed novel insights, including the identification of previously uncharacterized vaginal bacteria, features of the vaginal mycobiome and phageome, and differential expression of bacterial carbohydrate catabolic genes. Constructed from over 2,500 metagenomes and 4,000 bacterial genomes, VIRGO2 broadens geographic representation and microbial diversity compared to its predecessor. This updated catalog enables more precise profiling of taxonomic and functional composition from metagenomic and metatranscriptomic datasets. VIRGO2 is a critical resource for integrative analyses of vaginal microbial communities and their interactions with host tissues, thereby enhancing our mechanistic understanding of vaginal health and disease.
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Affiliation(s)
- M. T. France
- Center for Advanced Microbiome Research and Innovation, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD USA
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - I. Chaudry
- Center for Advanced Microbiome Research and Innovation, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD USA
| | - L. Rutt
- Center for Advanced Microbiome Research and Innovation, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD USA
| | - M. Quain
- Center for Advanced Microbiome Research and Innovation, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD USA
| | - B. Shirtliff
- Center for Advanced Microbiome Research and Innovation, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD USA
| | - E. McComb
- Center for Advanced Microbiome Research and Innovation, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD USA
| | - A. Maros
- Center for Advanced Microbiome Research and Innovation, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD USA
| | - M. Alizadeh
- Center for Advanced Microbiome Research and Innovation, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD USA
| | - F. A. Hussain
- Department of Biology, School of Arts and Sciences, Tufts University, Medford MA
| | - M. A. Elovitz
- Women’s Biomedical Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Obstetrics, Gynecology and Reproductive Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - D. A. Relman
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
- Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA
- Infectious Diseases Section, Veterans Affairs, Palo Alto Health Care System, Palo Alto, CA, USA
| | - A. Rahman
- Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
| | - R. M. Brotman
- Center for Advanced Microbiome Research and Innovation, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD USA
- Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA
| | - J. Price
- Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- UNC Global Projects–Zambia, Lusaka, Zambia
| | - M. Kassaro
- Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- UNC Global Projects–Zambia, Lusaka, Zambia
| | - J. B. Holm
- Center for Advanced Microbiome Research and Innovation, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD USA
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - B. Ma
- Center for Advanced Microbiome Research and Innovation, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD USA
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - J. Ravel
- Center for Advanced Microbiome Research and Innovation, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD USA
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA
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14
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Vande Moortele T, Verschaffelt P, Huang Q, Doncheva NT, Holstein T, Jachmann C, Dawyndt P, Martens L, Mesuere B, Van Den Bossche T. PathwayPilot: A User-Friendly Tool for Visualizing and Navigating Metabolic Pathways. Mol Cell Proteomics 2025; 24:100918. [PMID: 39880083 PMCID: PMC11903815 DOI: 10.1016/j.mcpro.2025.100918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 12/17/2024] [Accepted: 01/23/2025] [Indexed: 01/31/2025] Open
Abstract
Metaproteomics, the study of collective proteomes in environmental communities, plays a crucial role in understanding microbial functionalities affecting ecosystems and human health. Pathway analysis offers structured insights into the biochemical processes within these communities. However, no existing tool effectively combines pathway analysis with peptide- or protein-level data. We here introduce PathwayPilot, a web-based application designed to improve metaproteomic data analysis by integrating pathway analysis with peptide- and protein-level data, filling a critical gap in current metaproteomics bioinformatics tools. By allowing users to compare functional annotations across different samples or multiple organisms within a sample, PathwayPilot provides valuable insights into microbial functions. In the re-analysis of a study examining the effects of caloric restriction on gut microbiota, the tool successfully identified shifts in enzyme expressions linked to short-chain fatty acid biosynthesis, aligning with its original findings. PathwayPilot's user-friendly interface and robust capabilities make it a significant advancement in metaproteomics, with the potential for widespread application in microbial ecology and health sciences. All code is open source under the Apache2 license and is available at https://pathwaypilot.ugent.be.
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Affiliation(s)
- Tibo Vande Moortele
- Department of Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium
| | - Pieter Verschaffelt
- Department of Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium; VIB - UGent Center for Medical Biotechnology, VIB, Ghent, Belgium; Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Qingyao Huang
- Bioinformatics Systems Biology, Swiss Institute of Bioinformatics, Zurich, Switzerland; Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland
| | - Nadezhda T Doncheva
- Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark
| | - Tanja Holstein
- VIB - UGent Center for Medical Biotechnology, VIB, Ghent, Belgium; Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Caroline Jachmann
- VIB - UGent Center for Medical Biotechnology, VIB, Ghent, Belgium; Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Peter Dawyndt
- Department of Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium
| | - Lennart Martens
- VIB - UGent Center for Medical Biotechnology, VIB, Ghent, Belgium; Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Bart Mesuere
- Department of Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
| | - Tim Van Den Bossche
- VIB - UGent Center for Medical Biotechnology, VIB, Ghent, Belgium; Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
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15
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Huang YJ. The Microbiome in Asthma Heterogeneity: The Role of Multi-Omic Investigations. Immunol Rev 2025; 330:e70015. [PMID: 40072031 PMCID: PMC11899502 DOI: 10.1111/imr.70015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 02/13/2025] [Accepted: 02/28/2025] [Indexed: 03/15/2025]
Abstract
Asthma is one of the most prevalent and extensively studied chronic respiratory conditions, yet the heterogeneity of asthma remains biologically puzzling. Established factors like exogenous exposures and treatment adherence contribute to variability in asthma risk and clinical outcomes. It is also clear that the endogenous factors of genetics and immune system response patterns play key roles in asthma. Despite significant existing knowledge in the above, divergent clinical trajectories and outcomes are still observed, even among individuals with similar risk profiles, biomarkers, and optimal medical management. This suggests uncaptured biological interactions that contribute to asthma's heterogeneity, for which the role of host microbiota has lately attracted much research attention. This review will highlight recent evidence in this area, focusing on bedside-to-bench investigations that have leveraged omic technologies to uncover microbiome links to asthma outcomes and immunobiology. Studies centered on the respiratory system and the use of multi-omics are noted in particular. These represent a new generation of reverse-translational investigations revealing potential functional crosstalk in host microbiomes that may drive phenotypic heterogeneity in chronic diseases like asthma. Multi-omic data offer a wide lens into ecosystem interactions within a host. This informs new hypotheses and experimental work to elucidate mechanistic pathways for unresolved asthma endotypes. Further incorporation of multi-omics into patient-centered investigations can yield new insights that hopefully lead to even more precise, microbiome-informed strategies to reduce asthma burden.
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Affiliation(s)
- Yvonne J. Huang
- Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Department of Microbiology and ImmunologyUniversity of Michigan Medical SchoolAnn ArborMichiganUSA
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16
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Cui Z, Wu Y, Zhang QH, Wang SG, Guo ZH. NPENN: A Noise Perturbation Ensemble Neural Network for Microbiome Disease Phenotype Prediction. IEEE J Biomed Health Inform 2025; 29:2210-2221. [PMID: 40030297 DOI: 10.1109/jbhi.2024.3507789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/08/2025]
Abstract
With advances in microbiomics, the crucial role of microbes in disease progression is increasingly recognized. However, predicting disease phenotypes using microbiome data remains challenging due to data complexity, heterogeneity, and limited model generalization. Current methods often depend on specific datasets and are vulnerable to adversarial attacks. To address these issues, this paper introduces a novel Noise Perturbation Ensemble Neural Network model (NPENN), which combines noise mechanisms with Gradient Boosting (GB) techniques for robust neural network ensemble learning. NPENN, validated on multiple microbiome datasets, shows superior accuracy and generalization compared to traditional methods, effectively handling data complexity and variability. This approach enhances model robustness and feature learning by integrating GB prior knowledge. Additionally, the study explores microbial community roles in various diseases, providing insights into disease mechanisms and potential biomarkers for personalized precision diagnosis and treatment strategies.
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17
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Park H, Yeo S, Lee T, Han Y, Ryu CB, Huh CS. Culture-based characterization of gut microbiota in inflammatory bowel disease. Front Microbiol 2025; 16:1538620. [PMID: 40051478 PMCID: PMC11884817 DOI: 10.3389/fmicb.2025.1538620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 02/03/2025] [Indexed: 03/09/2025] Open
Abstract
Inflammatory bowel disease (IBD) is characterized by disruptions in the gut microbiome. While most studies on gut dysbiosis in IBD rely on sequencing-based methods, we employed a streamlined culturomics approach to obtain a more comprehensive understanding of gut microbiota imbalance in patients with IBD that may not be captured by sequencing alone. A total of 367 bacteria were identified at the species level, including 211 species from ulcerative colitis patients, 164 species from Crohn's disease (CD) patients, and 263 species from healthy individuals. Consistent with our 16S rRNA gene amplicon sequencing results, a significant decrease in microbial diversity and a severe imbalance, especially in CD patients, were also observed in the culture-based analysis. Our culturomics approach provided additional insights, highlighting dysbiosis in unique anaerobic and Gram-negative species in CD patients. Moreover, species-level findings for Bifidobacterium and Enterobacterales emphasized specific species expansions in IBD patients. Notably, Mediterraneibacter gnavus, Thomasclavelia ramosa, Parabacteroides merdae, and Collinsella aerofaciens are of particular clinical interest due to their correlation with inflammatory biomarkers. This comprehensive analysis underscores the value of integrating a culture-based approach with a genome-based approach to provide complementary insights and therapeutic targets in IBD.
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Affiliation(s)
- Hyunjoon Park
- Research Institute of Eco-friendly Livestock Science, Institute of Green-Bio Science and Technology, Seoul National University, Pyeongchang, Republic of Korea
| | - Soyoung Yeo
- Research Institute of Eco-friendly Livestock Science, Institute of Green-Bio Science and Technology, Seoul National University, Pyeongchang, Republic of Korea
- Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea
| | - Taekyu Lee
- Department of Internal Medicine, Digestive Disease Center and Research Institute, Soon Chun Hyang University School of Medicine, Bucheon, Republic of Korea
| | - Yumin Han
- Department of Internal Medicine, Digestive Disease Center and Research Institute, Soon Chun Hyang University School of Medicine, Bucheon, Republic of Korea
| | - Chang Beom Ryu
- Department of Internal Medicine, Digestive Disease Center and Research Institute, Soon Chun Hyang University School of Medicine, Bucheon, Republic of Korea
| | - Chul Sung Huh
- Research Institute of Eco-friendly Livestock Science, Institute of Green-Bio Science and Technology, Seoul National University, Pyeongchang, Republic of Korea
- Graduate School of International Agricultural Technology, Seoul National University, Pyeongchang, Republic of Korea
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18
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Lin T. Editorial: New techniques in microbiome research - volume II: Host-microbiome interactions using 'meta-omics' techniques. Front Cell Infect Microbiol 2025; 15:1541881. [PMID: 39991711 PMCID: PMC11843044 DOI: 10.3389/fcimb.2025.1541881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Accepted: 01/02/2025] [Indexed: 02/25/2025] Open
Affiliation(s)
- Tao Lin
- Department of Molecular Virology and Microbiology, Alkek Center for Metagenomics and
Microbiome Research, Baylor College of Medicine, Houston, TX, United States
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19
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Lista S, Munafò A, Caraci F, Imbimbo C, Emanuele E, Minoretti P, Pinto-Fraga J, Merino-País M, Crespo-Escobar P, López-Ortiz S, Monteleone G, Imbimbo BP, Santos-Lozano A. Gut microbiota in Alzheimer's disease: Understanding molecular pathways and potential therapeutic perspectives. Ageing Res Rev 2025; 104:102659. [PMID: 39800223 DOI: 10.1016/j.arr.2025.102659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 11/29/2024] [Accepted: 01/09/2025] [Indexed: 01/15/2025]
Abstract
Accumulating evidence suggests that gut microbiota (GM) plays a crucial role in Alzheimer's disease (AD) pathogenesis and progression. This narrative review explores the complex interplay between GM, the immune system, and the central nervous system in AD. We discuss mechanisms through which GM dysbiosis can compromise intestinal barrier integrity, enabling pro-inflammatory molecules and metabolites to enter systemic circulation and the brain, potentially contributing to AD hallmarks. Additionally, we examine other pathophysiological mechanisms by which GM may influence AD risk, including the production of short-chain fatty acids, secondary bile acids, and tryptophan metabolites. The role of the vagus nerve in gut-brain communication is also addressed. We highlight potential therapeutic implications of targeting GM in AD, focusing on antibiotics, probiotics, prebiotics, postbiotics, phytochemicals, and fecal microbiota transplantation. While preclinical studies showed promise, clinical evidence remains limited and inconsistent. We critically assess clinical trials, emphasizing challenges in translating GM-based therapies to AD patients. The reviewed evidence underscores the need for further research to elucidate precise molecular mechanisms linking GM to AD and determine whether GM dysbiosis is a contributing factor or consequence of AD pathology. Future studies should focus on large-scale clinical trials to validate GM-based interventions' efficacy and safety in AD.
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Affiliation(s)
- Simone Lista
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - Antonio Munafò
- Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence 50139, Italy.
| | - Filippo Caraci
- Department of Drug and Health Sciences, University of Catania, Catania 95125, Italy; Oasi Research Institute-IRCCS, Troina 94018, Italy.
| | - Camillo Imbimbo
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia 27100, Italy.
| | | | | | - José Pinto-Fraga
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - María Merino-País
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - Paula Crespo-Escobar
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - Susana López-Ortiz
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - Giovanni Monteleone
- Department of Systems Medicine, University of Rome Tor Vergata, Rome 00133, Italy; Unit of Gastroenterology, Policlinico Tor Vergata University Hospital, Rome 00133, Italy.
| | - Bruno P Imbimbo
- Department of Research and Development, Chiesi Farmaceutici, Parma 43122, Italy.
| | - Alejandro Santos-Lozano
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain; Physical Activity and Health Research Group (PaHerg), Research Institute of the Hospital 12 de Octubre ('imas12'), Madrid 28041, Spain.
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20
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Bai D, Ma C, Xun J, Luo H, Yang H, Lyu H, Zhu Z, Gai A, Yousuf S, Peng K, Xu S, Gao Y, Wang Y, Liu Y. MicrobiomeStatPlots: Microbiome statistics plotting gallery for meta-omics and bioinformatics. IMETA 2025; 4:e70002. [PMID: 40027478 PMCID: PMC11865346 DOI: 10.1002/imt2.70002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Revised: 01/21/2025] [Accepted: 01/23/2025] [Indexed: 03/05/2025]
Abstract
The rapid growth of microbiome research has generated an unprecedented amount of multi-omics data, presenting challenges in data analysis and visualization. To address these issues, we present MicrobiomeStatPlots, a comprehensive platform offering streamlined, reproducible tools for microbiome data analysis and visualization. This platform integrates essential bioinformatics workflows with multi-omics pipelines and provides 82 distinct visualization cases for interpreting microbiome datasets. By incorporating basic tutorials and advanced R-based visualization strategies, MicrobiomeStatPlots enhances accessibility and usability for researchers. Users can customize plots, contribute to the platform's expansion, and access a wealth of bioinformatics knowledge freely on GitHub (https://github.com/YongxinLiu/MicrobiomeStatPlot). Future plans include extending support for metabolomics, viromics, and metatranscriptomics, along with seamless integration of visualization tools into omics workflows. MicrobiomeStatPlots bridges gaps in microbiome data analysis and visualization, paving the way for more efficient, impactful microbiome research.
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Affiliation(s)
- Defeng Bai
- Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenChina
| | - Chuang Ma
- Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenChina
- School of HorticultureAnhui Agricultural UniversityHefeiChina
| | - Jiani Xun
- Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenChina
| | - Hao Luo
- Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenChina
| | - Haifei Yang
- Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenChina
- College of Life SciencesQingdao Agricultural UniversityQingdaoChina
| | - Hujie Lyu
- Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenChina
- Department of Food Science and NutritionThe Hong Kong Polytechnic UniversityHong KongSARChina
| | - Zhihao Zhu
- Zhanjiang Key Laboratory of Human Microecology and Clinical Translation Research, the Marine Biomedical Research Institute, College of Basic MedicineGuangdong Medical UniversityZhanjiangChina
| | - Anran Gai
- Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenChina
- School of Agricultural SciencesZhengzhou UniversityZhengzhouChina
| | - Salsabeel Yousuf
- Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenChina
| | - Kai Peng
- Jiangsu Co‐Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary MedicineYangzhou UniversityYangzhouChina
| | - Shanshan Xu
- School of Food and Biological EngineeringHefei University of TechnologyHefeiChina
| | - Yunyun Gao
- Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenChina
- School of Ecology and Nature ConservationBeijing Forestry UniversityBeijingChina
| | - Yao Wang
- Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenChina
| | - Yong‐Xin Liu
- Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenChina
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21
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Kennedy EC, Ross FC, O'Shea CA, Lavelle A, Ross P, Dempsey E, Stanton C, Hawkes CP. Observational study protocol: the faecal microbiome in the acute stage of new-onset paediatric type 1 diabetes in an Irish cohort. BMJ Open 2025; 15:e089206. [PMID: 39890137 PMCID: PMC11784173 DOI: 10.1136/bmjopen-2024-089206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 12/06/2024] [Indexed: 02/03/2025] Open
Abstract
INTRODUCTION Type 1 diabetes (T1D) is an autoimmune-mediated disorder caused by the destruction of pancreatic beta cells. Although there is an underlying genetic predisposition to developing T1D, the trigger is multifactorial and likely includes environmental factors. The intestinal microbiome has been identified as one such factor. Previous studies have illustrated differences in the microbiota of people with T1D compared with healthy controls. This study aims to describe the evolution of the microbiome and metabolome during the first year of clinical T1D, or stage 3 T1D diagnosis, and investigate whether there are differences in the microbiome and metabolome of children who present with and without diabetic ketoacidosis. The study will also explore possible associations between the microbiome, metabolome, glycaemic control and beta cell reserve. METHODS AND ANALYSIS This prospective cohort study will include children with newly diagnosed T1D and sibling controls (n=100, males and females) and their faecal microbiome will be characterised using shotgun metagenomic sequencing at multiple time points during the first year of diagnosis. We will develop a microbial culture biobank based on culturomic studies of stool samples from the healthy controls that will support future investigation. Metabolomic analysis will aim to identify additional biomarkers which may be involved in disease presentation and progression. Through this initial exploratory study, we aim to identify specific microbial biomarkers which may be used as future interventional targets throughout the various stages of T1D progression. ETHICS AND DISSEMINATION This study has been approved by the Clinical Research Ethics Committee of the Cork Teaching Hospitals. Study results will be available to patients with T1D and their families, carers, support networks and microbiome societies and other researchers. TRIAL REGISTRATION NUMBER The clinicaltrials.gov registration number for this trial is NCT06157736.
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Affiliation(s)
- Elaine Catherine Kennedy
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
- INFANT Research Centre, University College Cork, Cork, Ireland
| | - Fiona Catherine Ross
- Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | | | - Aonghus Lavelle
- Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Paul Ross
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Eugene Dempsey
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
- INFANT Research Centre, University College Cork, Cork, Ireland
- Department of Neonatology, Cork University Maternity Hospital, Cork, Ireland
| | - Catherine Stanton
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Teagasc Food Research Centre Moorepark, Moorepark, Ireland
| | - Colin Patrick Hawkes
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
- INFANT Research Centre, University College Cork, Cork, Ireland
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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22
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Al-Adham ISI, Agha ASAA, Al-Akayleh F, Al-Remawi M, Jaber N, Al Manasur M, Collier PJ. Prebiotics Beyond the Gut: Omics Insights, Artificial Intelligence, and Clinical Trials in Organ-Specific Applications. Probiotics Antimicrob Proteins 2025:10.1007/s12602-025-10465-x. [PMID: 39878922 DOI: 10.1007/s12602-025-10465-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/20/2025] [Indexed: 01/31/2025]
Abstract
Prebiotics, traditionally linked to gut health, are increasingly recognized for their systemic benefits, influencing multiple organ systems through interactions with the gut microbiota. Compounds like inulin, fructooligosaccharides (FOS), and galactooligosaccharides (GOS) enhance short-chain fatty acid (SCFA) production, benefiting neurocognitive health, cardiovascular function, immune modulation, and skin integrity. Advances in biotechnology, including deep eutectic solvents (DES) for extraction and machine learning (ML) for personalized formulations, have expanded prebiotic applications. Integrating these innovations with "omics" technologies enables precise microbial modulation, fostering personalized nutrition and precision therapies. This review examines organ-specific effects of prebiotics, highlights findings from clinical trials, and explores biotechnological innovations that enhance prebiotic efficacy, laying the groundwork for future personalized therapeutic strategies.
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Affiliation(s)
- Ibrahim S I Al-Adham
- Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, 11196, Jordan.
| | - Ahmed S A Ali Agha
- School of Pharmacy, Department of Pharmaceutical Sciences, The University of Jordan, Amman, 11942, Jordan
| | - Faisal Al-Akayleh
- Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, 11196, Jordan
| | - Mayyas Al-Remawi
- Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, 11196, Jordan
| | - Nisrein Jaber
- Faculty of Pharmacy, Al Zaytoonah University of Jordan, Amman, 11733, Jordan
| | - Manar Al Manasur
- Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, 11196, Jordan
| | - Phillip J Collier
- Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, 11196, Jordan.
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23
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Misu IJ, Kayess MO, Siddiqui MN, Gupta DR, Islam MN, Islam T. Microbiome Engineering for Sustainable Rice Production: Strategies for Biofertilization, Stress Tolerance, and Climate Resilience. Microorganisms 2025; 13:233. [PMID: 40005600 PMCID: PMC11857137 DOI: 10.3390/microorganisms13020233] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 01/11/2025] [Accepted: 01/14/2025] [Indexed: 02/27/2025] Open
Abstract
The plant microbiome, found in the rhizosphere, phyllosphere, and endosphere, is essential for nutrient acquisition, stress tolerance, and the overall health of plants. This review aims to update our knowledge of and critically discuss the diversity and functional roles of the rice microbiome, as well as microbiome engineering strategies to enhance biofertilization and stress resilience. Rice hosts various microorganisms that affect nutrient cycling, growth promotion, and resistance to stresses. Microorganisms carry out these functions through nitrogen fixation, phytohormone and metabolite production, enhanced nutrient solubilization and uptake, and regulation of host gene expression. Recent research on molecular biology has elucidated the complex interactions within rice microbiomes and the signalling mechanisms that establish beneficial microbial communities, which are crucial for sustainable rice production and environmental health. Crucial factors for the successful commercialization of microbial agents in rice production include soil properties, practical environmental field conditions, and plant genotype. Advances in microbiome engineering, from traditional inoculants to synthetic biology, optimize nutrient availability and enhance resilience to abiotic stresses like drought. Climate change intensifies these challenges, but microbiome innovations and microbiome-shaping genes (M genes) offer promising solutions for crop resilience. This review also discusses the environmental and agronomic implications of microbiome engineering, emphasizing the need for further exploration of M genes for breeding disease resistance traits. Ultimately, we provide an update to the current findings on microbiome engineering in rice, highlighting pathways to enhance crop productivity sustainably while minimizing environmental impacts.
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Affiliation(s)
- Israt Jahan Misu
- Institute of Biotechnology and Genetic Engineering (IBGE), Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur 1706, Bangladesh; (I.J.M.); (M.O.K.); (D.R.G.)
| | - Md. Omar Kayess
- Institute of Biotechnology and Genetic Engineering (IBGE), Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur 1706, Bangladesh; (I.J.M.); (M.O.K.); (D.R.G.)
| | - Md. Nurealam Siddiqui
- Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur 1706, Bangladesh;
| | - Dipali Rani Gupta
- Institute of Biotechnology and Genetic Engineering (IBGE), Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur 1706, Bangladesh; (I.J.M.); (M.O.K.); (D.R.G.)
| | - M. Nazrul Islam
- Centre for Plant and Soil Health, Regenerative Agri-Science Canada Inc., Winnipeg, MB R3T 5L2, Canada
| | - Tofazzal Islam
- Institute of Biotechnology and Genetic Engineering (IBGE), Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur 1706, Bangladesh; (I.J.M.); (M.O.K.); (D.R.G.)
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24
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Reuben RC, Torres C. Integrating the milk microbiome signatures in mastitis: milk-omics and functional implications. World J Microbiol Biotechnol 2025; 41:41. [PMID: 39826029 PMCID: PMC11742929 DOI: 10.1007/s11274-024-04242-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 12/26/2024] [Indexed: 01/20/2025]
Abstract
Mammalian milk contains a variety of complex bioactive and nutritional components and microorganisms. These microorganisms have diverse compositions and functional roles that impact host health and disease pathophysiology, especially mastitis. The advent and use of high throughput omics technologies, including metagenomics, metatranscriptomics, metaproteomics, metametabolomics, as well as culturomics in milk microbiome studies suggest strong relationships between host phenotype and milk microbiome signatures in mastitis. While single omics studies have undoubtedly contributed to our current understanding of milk microbiome and mastitis, they often provide limited information, targeting only a single biological viewpoint which is insufficient to provide system-wide information necessary for elucidating the biological footprints and molecular mechanisms driving mastitis and milk microbiome dysbiosis. Therefore, integrating a multi-omics approach in milk microbiome research could generate new knowledge, improve the current understanding of the functional and structural signatures of the milk ecosystem, and provide insights for sustainable mastitis control and microbiome management.
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Affiliation(s)
- Rine Christopher Reuben
- Biology Department, King's College, 133 North River Street, Wilkes-Barre, PA, 18711, USA.
- Area of Biochemistry and Molecular Biology, OneHealth-UR Research Group, University of La Rioja, 26006, Logroño, Spain.
| | - Carmen Torres
- Area of Biochemistry and Molecular Biology, OneHealth-UR Research Group, University of La Rioja, 26006, Logroño, Spain
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25
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Zeng J, Cheong LYT, Lo CH. Therapeutic targeting of obesity-induced neuroinflammation and neurodegeneration. Front Endocrinol (Lausanne) 2025; 15:1456948. [PMID: 39897964 PMCID: PMC11781992 DOI: 10.3389/fendo.2024.1456948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 12/30/2024] [Indexed: 02/04/2025] Open
Abstract
Obesity is a major modifiable risk factor leading to neuroinflammation and neurodegeneration. Excessive fat storage in obesity promotes the progressive infiltration of immune cells into adipose tissue, resulting in the release of pro-inflammatory factors such as cytokines and adipokines. These inflammatory mediators circulate through the bloodstream, propagating inflammation both in the periphery and in the central nervous system. Gut dysbiosis, which results in a leaky intestinal barrier, exacerbates inflammation and plays a significant role in linking obesity to the pathogenesis of neuroinflammation and neurodegeneration through the gut-brain/gut-brain-liver axis. Inflammatory states within the brain can lead to insulin resistance, mitochondrial dysfunction, autolysosomal dysfunction, and increased oxidative stress. These disruptions impair normal neuronal function and subsequently lead to cognitive decline and motor deficits, similar to the pathologies observed in major neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis, and Parkinson's disease. Understanding the underlying disease mechanisms is crucial for developing therapeutic strategies to address defects in these inflammatory and metabolic pathways. In this review, we summarize and provide insights into different therapeutic strategies, including methods to alter gut dysbiosis, lifestyle changes, dietary supplementation, as well as pharmacological agents derived from natural sources, that target obesity-induced neuroinflammation and neurodegeneration.
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Affiliation(s)
- Jialiu Zeng
- Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY, United States
- Interdisciplinary Neuroscience Program, Syracuse University, Syracuse, NY, United States
| | - Lenny Yi Tong Cheong
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Chih Hung Lo
- Interdisciplinary Neuroscience Program, Syracuse University, Syracuse, NY, United States
- Department of Biology, Syracuse University, Syracuse, NY, United States
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26
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Wawryk MMH, Ley P, Vasquez-Cardenas D, Tabor RF, Cook PLM. Multidisciplinary methodologies used in the study of cable bacteria. FEMS Microbiol Rev 2025; 49:fuae030. [PMID: 39673715 PMCID: PMC11774119 DOI: 10.1093/femsre/fuae030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 10/21/2024] [Accepted: 12/11/2024] [Indexed: 12/16/2024] Open
Abstract
Cable bacteria are a unique type of filamentous microorganism that can grow up to centimetres long and are capable of long-distance electron transport over their entire lengths. Due to their unique metabolism and conductive capacities, the study of cable bacteria has required technical innovations, both in adapting existing techniques and developing entirely new ones. This review discusses the existing methods used to study eight distinct aspects of cable bacteria research, including the challenges of culturing them in laboratory conditions, performing physical and biochemical extractions, and analysing the conductive mechanism. As cable bacteria research requires an interdisciplinary approach, methods from a range of fields are discussed, such as biogeochemistry, genomics, materials science, and electrochemistry. A critical analysis of the current state of each approach is presented, highlighting the advantages and drawbacks of both commonly used and emerging methods.
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Affiliation(s)
| | - Philip Ley
- Department of Biology, University of Antwerp, Wilrijk 2020, Belgium
| | | | - Rico F Tabor
- School of Chemistry, Monash University, Clayton 3800 VIC, Australia
| | - Perran L M Cook
- School of Chemistry, Monash University, Clayton 3800 VIC, Australia
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27
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Fan S, Qin P, Lu J, Wang S, Zhang J, Wang Y, Cheng A, Cao Y, Ding W, Zhang W. Bioprospecting of culturable marine biofilm bacteria for novel antimicrobial peptides. IMETA 2024; 3:e244. [PMID: 39742298 PMCID: PMC11683478 DOI: 10.1002/imt2.244] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 09/25/2024] [Accepted: 09/27/2024] [Indexed: 01/03/2025]
Abstract
Antimicrobial peptides (AMPs) have become a viable source of novel antibiotics that are effective against human pathogenic bacteria. In this study, we construct a bank of culturable marine biofilm bacteria constituting 713 strains and their nearly complete genomes and predict AMPs using ribosome profiling and deep learning. Compared with previous approaches, ribosome profiling has improved the identification and validation of small open reading frames (sORFs) for AMP prediction. Among the 80,430 expressed sORFs, 341 are identified as candidate AMPs with high probability. Most potential AMPs have less than 40% similarity in their amino acid sequence compared to those listed in public databases. Furthermore, these AMPs are associated with bacterial groups that are not previously known to produce AMPs. Therefore, our deep learning model has acquired characteristics of unfamiliar AMPs. Chemical synthesis of 60 potential AMP sequences yields 54 compounds with antimicrobial activity, including potent inhibitory effects on various drug-resistant human pathogens. This study extends the range of AMP compounds by investigating marine biofilm microbiomes using a novel approach, accelerating AMP discovery.
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Affiliation(s)
- Shen Fan
- MOE Key Laboratory of Evolution & Marine Biodiversity and Institute of Evolution & Marine BiodiversityOcean University of ChinaQingdaoChina
| | - Peng Qin
- MOE Key Laboratory of Evolution & Marine Biodiversity and Institute of Evolution & Marine BiodiversityOcean University of ChinaQingdaoChina
| | - Jie Lu
- MOE Key Laboratory of Evolution & Marine Biodiversity and Institute of Evolution & Marine BiodiversityOcean University of ChinaQingdaoChina
| | - Shuaitao Wang
- MOE Key Laboratory of Evolution & Marine Biodiversity and Institute of Evolution & Marine BiodiversityOcean University of ChinaQingdaoChina
| | - Jie Zhang
- MOE Key Laboratory of Evolution & Marine Biodiversity and Institute of Evolution & Marine BiodiversityOcean University of ChinaQingdaoChina
| | - Yan Wang
- MOE Key Laboratory of Evolution & Marine Biodiversity and Institute of Evolution & Marine BiodiversityOcean University of ChinaQingdaoChina
| | - Aifang Cheng
- Department of Biomedical Sciences, Faculty of Health SciencesUniversity of MacauTaipaMacao SARChina
| | - Yan Cao
- College of Pulmonary & Critical Care MedicineChinese PLA General HospitalBeijingChina
| | - Wei Ding
- MOE Key Laboratory of Marine Genetics & Breeding and College of Marine Life SciencesOcean University of ChinaQingdaoChina
| | - Weipeng Zhang
- MOE Key Laboratory of Evolution & Marine Biodiversity and Institute of Evolution & Marine BiodiversityOcean University of ChinaQingdaoChina
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28
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Chen S, Jiao Y, Han C, Li Y, Zou W, Liu J. Drug-Resistant Epilepsy and Gut-Brain Axis: an Overview of a New Strategy for Treatment. Mol Neurobiol 2024; 61:10023-10040. [PMID: 38087164 DOI: 10.1007/s12035-023-03757-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 10/30/2023] [Indexed: 11/24/2024]
Abstract
Drug-resistant epilepsy (DRE), also known as intractable epilepsy or refractory epilepsy, is a disease state with long-term poorly controlled seizures attack. Without effective treatment, patients are at an elevated risk of injury, premature death, mental disorders, and poor quality of life, increasing the need for a fresh perspective on the etiology and treatment of DRE. The gut is known to harbor a wide variety of microorganisms that can regulate the host's response to exogenous signals and participate in various physiological and pathological processes in the human body. Interestingly, emerging evidence has uncovered the changes in gut microbiota in patients with epilepsy, particularly those with DRE. In addition, both dietary interventions and specific antibiotic therapy have been proven to be effective in restoring the microecological environment and, more importantly, reducing seizures. Here, we reviewed recent studies on DRE and the involvement of gut microbiota in it, describing changes in the gut microflora composition in patients with DRE and corresponding animal models. Furthermore, the influence of the ketogenic diet, probiotics, fecal microbiota transplantation (FMT), and antibiotics as microbiome-related factors on seizure control and its possible mechanisms are broadly discussed. Finally, we highlighted the significance of gut microbiome in DRE, in order to provide a new prospect for early identification and individualized treatment of patients with DRE.
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Affiliation(s)
- Shuna Chen
- Stem Cell Clinical Research Center, National Joint Engineering Laboratory, Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China
- Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, People's Republic of China
| | - Yang Jiao
- Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, People's Republic of China
- Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China
| | - Chao Han
- Stem Cell Clinical Research Center, National Joint Engineering Laboratory, Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China
- Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, People's Republic of China
| | - Ying Li
- Stem Cell Clinical Research Center, National Joint Engineering Laboratory, Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China
- Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, People's Republic of China
| | - Wei Zou
- Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, People's Republic of China.
| | - Jing Liu
- Stem Cell Clinical Research Center, National Joint Engineering Laboratory, Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China.
- Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, People's Republic of China.
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29
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Ouwehand J, Peijnenburg WJGM, Vijver MG. Microbial function matters: Microbiome-aware nano-ecotoxicology needs functional endpoints besides compositional data. CHEMOSPHERE 2024; 369:143905. [PMID: 39643017 DOI: 10.1016/j.chemosphere.2024.143905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 12/03/2024] [Accepted: 12/03/2024] [Indexed: 12/09/2024]
Abstract
The microbiome provides an active barrier to the external environment and aids in the metabolism of the host. Nanomaterials are known to interact with this microbiome host plane. Given the recent advances in techniques to study the microbiome, there has been a vast increase in studies trying to find causality in host response via the microbiome in nano-ecotoxicology. Our review integrates the latest advancements in understanding the microbiome's role in elucidating host health related to nanomaterial exposure, thereby explicitly emphasizing the gap between compositional and functional studies. Both the techniques used to interfere and the current understanding of microbiome-host relationships in nano-ecotoxicology are discussed. To further highlight the functional side of the microbiome, we performed an explorative meta-analysis to bridge the gap between top-down and bottom-up studies. This review gives a perspective on generalising microbiome-aware nano-ecotoxicology and discusses methodologies to enhance the interpretation of nanomaterial or chemical exposure to host-microbiome interactions. The current study discloses that correlations built on compositional data are not a good proxy for host outcome and more in-depth analysis coupled with functional analysis should be explored more in microbiome-aware nano-ecotoxicology.
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Affiliation(s)
- Jesse Ouwehand
- Institute of Environmental Sciences (CML), Leiden University, P.O. Box 9518, Leiden, 2300, RA, the Netherlands.
| | - Willie J G M Peijnenburg
- Institute of Environmental Sciences (CML), Leiden University, P.O. Box 9518, Leiden, 2300, RA, the Netherlands; National Institute of Public Health and the Environment (RIVM), P.O. Box 1, Bilthoven, the Netherlands
| | - Martina G Vijver
- Institute of Environmental Sciences (CML), Leiden University, P.O. Box 9518, Leiden, 2300, RA, the Netherlands
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30
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Aggeletopoulou I, Triantos C. Microbiome Shifts and Their Impact on Gut Physiology in Irritable Bowel Syndrome. Int J Mol Sci 2024; 25:12395. [PMID: 39596460 PMCID: PMC11594715 DOI: 10.3390/ijms252212395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 11/17/2024] [Accepted: 11/18/2024] [Indexed: 11/28/2024] Open
Abstract
Irritable bowel syndrome (IBS) is one of the most prevalent functional gastrointestinal disorders characterized by recurrent abdominal pain and altered bowel habits. The exact pathophysiological mechanisms for IBS development are not completely understood. Several factors, including genetic predisposition, environmental and psychological influences, low-grade inflammation, alterations in gastrointestinal motility, and dietary habits, have been implicated in the pathophysiology of the disorder. Additionally, emerging evidence highlights the role of gut microbiota in the pathophysiology of IBS. This review aims to thoroughly investigate how alterations in the gut microbiota impact physiological functions such as the brain-gut axis, immune system activation, mucosal inflammation, gut permeability, and intestinal motility. Our research focuses on the dynamic "microbiome shifts", emphasizing the enrichment or depletion of specific bacterial taxa in IBS and their profound impact on disease progression and pathology. The data indicated that specific bacterial populations are implicated in IBS, including reductions in beneficial species such as Lactobacillus and Bifidobacterium, along with increases in potentially harmful bacteria like Firmicutes and Proteobacteria. Emphasis is placed on the imperative need for further research to delineate the role of specific microbiome alterations and their potential as therapeutic targets, providing new insights into personalized treatments for IBS.
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Affiliation(s)
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece;
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31
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Pérez-Prieto I, Plaza-Florido A, Ubago-Guisado E, Ortega FB, Altmäe S. Physical activity, sedentary behavior and microbiome: A systematic review and meta-analysis. J Sci Med Sport 2024; 27:793-804. [PMID: 39048485 DOI: 10.1016/j.jsams.2024.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 05/18/2024] [Accepted: 07/02/2024] [Indexed: 07/27/2024]
Abstract
BACKGROUND The effects of physical activity and sedentary behavior on human health are well known, however, the molecular mechanisms are poorly understood. Growing evidence points to physical activity as an important modulator of the composition and function of microbial communities, while evidence of sedentary behavior is scarce. We aimed to synthesize and meta-analyze the current evidence about the effects of physical activity and sedentary behavior on microbiome across different body sites and in different populations. METHODS A systematic search in PubMed, Web of Science, Scopus and Cochrane databases was conducted until September 2022. Random-effects meta-analyses including cross-sectional studies (active vs. inactive/athletes vs. non-athletes) or trials reporting the chronic effect of physical activity interventions on gut microbiome alpha-diversity in healthy individuals were performed. RESULTS Ninety-one studies were included in this systematic review. Our meta-analyses of 2632 participants indicated no consistent effect of physical activity on microbial alpha-diversity, although there seems to be a trend toward a higher microbial richness in athletes compared to non-athletes. Most of studies reported an increase in short-chain fatty acid-producing bacteria such as Akkermansia, Faecalibacterium, Veillonella or Roseburia in active individuals and after physical activity interventions. CONCLUSIONS Physical activity levels were positively associated with the relative abundance of short-chain fatty acid-producing bacteria. Athletes seem to have a richer microbiome compared to non-athletes. However, high heterogeneity between studies avoids obtaining conclusive information on the role of physical activity in microbial composition. Future multi-omics studies would enhance our understanding of the molecular effects of physical activity and sedentary behavior on the microbiome.
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Affiliation(s)
- Inmaculada Pérez-Prieto
- Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Spain.
| | - Abel Plaza-Florido
- Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS), University of Granada, Spain; Pediatric Exercise and Genomics Research Center, UC Irvine School of Medicine, United States.
| | - Esther Ubago-Guisado
- Instituto de Investigación Biosanitaria ibs.GRANADA, Spain; Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS), University of Granada, Spain
| | - Francisco B Ortega
- Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS), University of Granada, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Granada, Spain; Faculty of Sport and Health Sciences, University of Jyväskylä, Finland.
| | - Signe Altmäe
- Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Spain; Division of Obstetrics and Gynaecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Huddinge, Stockholm, Sweden; Department of Gynaecology and Reproductive Medicine, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
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32
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Duong VA, Enkhbayar A, Bhasin N, Senavirathna L, Preisner EC, Hoffman KL, Shukla R, Jenq RR, Cheng K, Bronner MP, Figeys D, Britton RA, Pan S, Chen R. A complementary metaproteomic approach to interrogate microbiome cultivated from clinical colon biopsies. Proteomics 2024; 24:e2400078. [PMID: 38824665 PMCID: PMC11576236 DOI: 10.1002/pmic.202400078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 05/17/2024] [Accepted: 05/22/2024] [Indexed: 06/04/2024]
Abstract
The human gut microbiome plays a vital role in preserving individual health and is intricately involved in essential functions. Imbalances or dysbiosis within the microbiome can significantly impact human health and are associated with many diseases. Several metaproteomics platforms are currently available to study microbial proteins within complex microbial communities. In this study, we attempted to develop an integrated pipeline to provide deeper insights into both the taxonomic and functional aspects of the cultivated human gut microbiomes derived from clinical colon biopsies. We combined a rapid peptide search by MSFragger against the Unified Human Gastrointestinal Protein database and the taxonomic and functional analyses with Unipept Desktop and MetaLab-MAG. Across seven samples, we identified and matched nearly 36,000 unique peptides to approximately 300 species and 11 phyla. Unipept Desktop provided gene ontology, InterPro entries, and enzyme commission number annotations, facilitating the identification of relevant metabolic pathways. MetaLab-MAG contributed functional annotations through Clusters of Orthologous Genes and Non-supervised Orthologous Groups categories. These results unveiled functional similarities and differences among the samples. This integrated pipeline holds the potential to provide deeper insights into the taxonomy and functions of the human gut microbiome for interrogating the intricate connections between microbiome balance and diseases.
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Affiliation(s)
- Van-An Duong
- The Brown Foundation Institute of Molecular Medicine, McGovern Medical School/ The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Altai Enkhbayar
- The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX 77030, USA
| | - Nobel Bhasin
- Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA Baylor College of Medicine, Houston, TX 77030
| | - Lakmini Senavirathna
- The Brown Foundation Institute of Molecular Medicine, McGovern Medical School/ The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Eva C Preisner
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Kristi L Hoffman
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Richa Shukla
- Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA Baylor College of Medicine, Houston, TX 77030
| | - Robert R Jenq
- The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX 77030, USA
- Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Kai Cheng
- School of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Mary P Bronner
- Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA
| | - Daniel Figeys
- School of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Robert A Britton
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Sheng Pan
- The Brown Foundation Institute of Molecular Medicine, McGovern Medical School/ The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
- The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX 77030, USA
| | - Ru Chen
- Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA Baylor College of Medicine, Houston, TX 77030
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Mancini A, Vitucci D, Lasorsa VA, Lupo C, Brustio PR, Capasso M, Orrù S, Rainoldi A, Schena F, Buono P. Six months of different exercise type in sedentary primary schoolchildren: impact on physical fitness and saliva microbiota composition. Front Nutr 2024; 11:1465707. [PMID: 39512522 PMCID: PMC11542257 DOI: 10.3389/fnut.2024.1465707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 10/15/2024] [Indexed: 11/15/2024] Open
Abstract
Introduction Lifestyle influences microbiota composition. We previously reported a healthier microbiota composition in saliva from active schoolchildren compared to sedentary. In the present study, we evaluated the effects of 6 months of different exercise types on physical fitness and saliva microbiota composition in 8-11-years-old sedentary schoolchildren. Methods Sixty-four sedentary children from five primary schools in Turin, Italy, were divided into three groups: one continued normal curricular activity while two underwent different exercise protocols for 6 months. The Structured Exercise (Sa) group did 2 h per week of muscle activation, strength and coordination exercises supervised by a kinesiologist. The Daily Mile (Dm) group did 1 h per week of Sa plus 15 min of walking/running outdoors four times a week, supervised by a class teacher; control group (Ct) did 2 h a week of curricular exercise supervised by a class teacher. Physical fitness was evaluated before and after the intervention. Saliva samples were collected post-intervention in all participants and analyzed using PCR amplification of 16S rRNA bacterial genes. The Amplicon Sequence Variants were filtered, decontaminated, and phylogenetically classified using DADA2 software. Differential abundance analysis of microbiome taxa and pathway data was conducted using the LEfSe algorithm and PICRUSt. Results The Sa group showed better performances in lower limb power and sprint performance while both the Sa and Dm groups improved in endurance and balance at the end of the intervention; only balance resulted slightly improved in the Ct group. Among the genera differently enriched in saliva after the training intervention, we found that the Prevotella, the Dubosiella and the Family XIII AD3011 group were the most abundant in the Sa group; differently, the Neisseria and the Abiotrophia in Ct group. Four species showed significant the Prevotella melaninogenica and the Prevotella nanceiensis were more abundant in the Sa, conversely, Gemella sanguinis was enriched in Dm and Abiotrophia defectiva in Ct saliva group. Conclusion We demonstrated that Sa and Dm, not curricular exercise, improve the physical fitness components in sedentary schoolchildren correlated to health and promote an enrichment in saliva microbiota species associated to a healthier profile.
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Affiliation(s)
- Annamaria Mancini
- Department of Medicine, Movement Sciences and Wellness, University Parthenope, Naples, Italy
- CEINGE-Biotecnologie Avanzate “Franco Salvatore”, Napoli, Italy
| | - Daniela Vitucci
- Department of Medicine, Movement Sciences and Wellness, University Parthenope, Naples, Italy
- CEINGE-Biotecnologie Avanzate “Franco Salvatore”, Napoli, Italy
| | | | - Corrado Lupo
- Department of Medical Sciences, University of Turin, Turin, Italy
| | | | - Mario Capasso
- CEINGE-Biotecnologie Avanzate “Franco Salvatore”, Napoli, Italy
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy
| | - Stefania Orrù
- Department of Medicine, Movement Sciences and Wellness, University Parthenope, Naples, Italy
- CEINGE-Biotecnologie Avanzate “Franco Salvatore”, Napoli, Italy
| | - Alberto Rainoldi
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Federico Schena
- Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy
| | - Pasqualina Buono
- Department of Medicine, Movement Sciences and Wellness, University Parthenope, Naples, Italy
- CEINGE-Biotecnologie Avanzate “Franco Salvatore”, Napoli, Italy
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Brennan C, Belda-Ferre P, Zuffa S, Charron-Lamoureux V, Mohanty I, Ackermann G, Allaband C, Ambre M, Boyer T, Bryant M, Cantrell K, Gonzalez A, McDonald D, Salido RA, Song SJ, Wright G, Dorrestein PC, Knight R. Clearing the plate: a strategic approach to mitigate well-to-well contamination in large-scale microbiome studies. mSystems 2024; 9:e0098524. [PMID: 39283083 PMCID: PMC11494942 DOI: 10.1128/msystems.00985-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 08/06/2024] [Indexed: 10/23/2024] Open
Abstract
Large-scale studies are essential to answer questions about complex microbial communities that can be extremely dynamic across hosts, environments, and time points. However, managing acquisition, processing, and analysis of large numbers of samples poses many challenges, with cross-contamination being the biggest obstacle. Contamination complicates analysis and results in sample loss, leading to higher costs and constraints on mixed sample type study designs. While many researchers opt for 96-well plates for their workflows, these plates present a significant issue: the shared seal and weak separation between wells leads to well-to-well contamination. To address this concern, we propose an innovative high-throughput approach, termed as the Matrix method, which employs barcoded Matrix Tubes for sample acquisition. This method is complemented by a paired nucleic acid and metabolite extraction, utilizing 95% (vol/vol) ethanol to stabilize microbial communities and as a solvent for extracting metabolites. Comparative analysis between conventional 96-well plate extractions and the Matrix method, measuring 16S rRNA gene levels via quantitative polymerase chain reaction, demonstrates a notable decrease in well-to-well contamination with the Matrix method. Metagenomics, 16S rRNA gene amplicon sequencing (16S), and untargeted metabolomics analysis via liquid chromatography-tandem mass spectrometry (LC-MS/MS) confirmed that the Matrix method recovers reproducible microbial and metabolite compositions that can distinguish between subjects. This advancement is critical for large-scale study design as it minimizes well-to-well contamination and technical variation, shortens processing times, and integrates with automated infrastructure for enhancing sample randomization and metadata generation. IMPORTANCE Understanding dynamic microbial communities typically requires large-scale studies. However, handling large numbers of samples introduces many challenges, with cross-contamination being a major issue. It not only complicates analysis but also leads to sample loss and increased costs and restricts diverse study designs. The prevalent use of 96-well plates for nucleic acid and metabolite extractions exacerbates this problem due to their wells having little separation and being connected by a single plate seal. To address this, we propose a new strategy using barcoded Matrix Tubes, showing a significant reduction in cross-contamination compared to conventional plate-based approaches. Additionally, this method facilitates the extraction of both nucleic acids and metabolites from a single tubed sample, eliminating the need to collect separate aliquots for each extraction. This innovation improves large-scale study design by shortening processing times, simplifying analysis, facilitating metadata curation, and producing more reliable results.
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Affiliation(s)
- Caitriona Brennan
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
- Division of Biological Sciences, University of California San Diego, La Jolla, California, USA
| | - Pedro Belda-Ferre
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Simone Zuffa
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, California, USA
| | - Vincent Charron-Lamoureux
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, California, USA
| | - Ipsita Mohanty
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, California, USA
| | - Gail Ackermann
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Celeste Allaband
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Madison Ambre
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Tara Boyer
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - MacKenzie Bryant
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Kalen Cantrell
- Department of Computer Science and Engineering, University of California, San Diego, La Jolla, California, USA
| | - Antonio Gonzalez
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Daniel McDonald
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Rodolfo A. Salido
- Department of Bioengineering, University of California, San Diego, La Jolla, California, USA
| | - Se Jin Song
- Center for Microbiome Innovation, University of California, San Diego, La Jolla, California, USA
| | - Gillian Wright
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Pieter C. Dorrestein
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, California, USA
- Center for Microbiome Innovation, University of California, San Diego, La Jolla, California, USA
| | - Rob Knight
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
- Department of Computer Science and Engineering, University of California, San Diego, La Jolla, California, USA
- Department of Bioengineering, University of California, San Diego, La Jolla, California, USA
- Center for Microbiome Innovation, University of California, San Diego, La Jolla, California, USA
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Jiang S, Pei L, Chen L, Sun J, Song Y. Mechanisms of Electroacupuncture in Alleviating Visceral Hypersensitivity in Post-Infectious Irritable Bowel Syndrome Mice: The Role of GDNF Signaling Pathway and Gut Microbiota. Microb Physiol 2024; 34:255-263. [PMID: 39396501 DOI: 10.1159/000541888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 10/07/2024] [Indexed: 10/15/2024]
Abstract
INTRODUCTION Post-infectious irritable bowel syndrome (PI-IBS) is a functional bowel disease that develops following an acute gastrointestinal infection. Electroacupuncture (EA) can regulate the gut microbiota and alleviate visceral hypersensitivity. Glial cell-derived neurotrophic factor (GDNF) is a potential factor in visceral hypersensitivity reactions. The aim of this study was to explore whether EA could alleviate visceral hypersensitivity in PI-IBS by regulating gut microbiota through GDNF signaling. METHODS 2,4,6-trinitrobenzene sulfonic acid was used to induce visceral hypersensitivity in PI-IBS mice. Intestinal visceral sensitivity was assessed by using the abdominal withdrawal reflex (colorectal distention). 16S ribosomal RNA sequencing profiles the gut microbiome community. RESULTS GDNF can exacerbate the imbalances of the gut microbiota and increase visceral hypersensitivity compared with the model group. Whereas EA treatment increases the richness and diversity of the gut microbiota, decreases differences among species and alleviates visceral sensitivity. CONCLUSION EA can alleviate visceral hypersensitivity in PI-IBS by regulating the gut microbiota via GDNF signaling, providing new insights for mechanistic research on EA in PI-IBS treatment.
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Affiliation(s)
- Shiyuan Jiang
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China,
- Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China,
- Acupuncture and Massage College, Health and Rehabilitation College, Nanjing University of Chinese Medicine, Nanjing, China,
| | - Lixia Pei
- Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lu Chen
- Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jianhua Sun
- Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yafang Song
- Acupuncture and Massage College, Health and Rehabilitation College, Nanjing University of Chinese Medicine, Nanjing, China
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Hiremath G, Choksi Y, Correa H, Jacobse J, Das SR, Ma S, Goettel JA, Rajagopala SV. Children with eosinophilic esophagitis non-responsive to combination therapy have distinct esophageal transcriptomic and microbiome profile. Allergy 2024; 79:2798-2811. [PMID: 38993131 PMCID: PMC11528550 DOI: 10.1111/all.16208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 04/22/2024] [Accepted: 06/03/2024] [Indexed: 07/13/2024]
Abstract
BACKGROUND A combination of proton-pump inhibitors (PPI) and topical steroids (TS) is used to treat children with eosinophilic esophagitis (EoE). However, a subset of children do not respond to this combination therapy. We aimed to identify the esophageal transcriptional, cell composition, and microbial differences between the non-responders (EoE-PPI-TSnr; n = 7) and responders (EoE-PPI-TSr; n = 7) to the combination therapy for EoE and controls (n = 9) using metatranscriptomics. METHODS Differential gene expression analysis was used to identify transcriptional differences, validated using the EoE diagnostic panel (EDP). Deconvolution analysis was performed to identify differences in their cell type composition. Microbiome analysis was conducted from esophageal biopsies RNAseq data, and microbial abundance was correlated with esophageal gene expression. RESULTS In all, 3164 upregulated and 3154 downregulated genes distinguished EoE-PPI-TSnr from EoE-PPI-TSr. Eosinophilic inflammatory response, cytokine signaling, and collagen formation pathways were significantly upregulated in EoE-PPI-TSnr. There was a 56% overlap in dysregulated genes between EoE-PPI-TSnr and EDP, with a perfect agreement in the directionality of modulation. Eosinophils, dendritic cells (DCs), immature DCs, megakaryocytic-erythroid progenitors, and T helper type 1 cells were significantly higher in EoE-PPI-TSnr. There was no significant difference in microbiome diversity. The relative abundance of Fusobacterium sp. and Acinetobacter sp. notably differed in EoE-PPI-TSnr and correlated with the key pathways. CONCLUSION Our results provide critical insights into the molecular, cellular, and microbial factors associated with the lack of response to PPI and TS combination therapy in children with EoE. This study advances our understanding of the pathobiology of EoE while guiding personalized treatment strategies.
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Affiliation(s)
- Girish Hiremath
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Vanderbilt Children's Hospital, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Yash Choksi
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Tennesee Valley Health System, Veteran's Affairs, Nashville, Tennessee, USA
| | - Hernan Correa
- Division of Pathology, Vanderbilt Children's Hospital, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Justin Jacobse
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Willem-Alexander Children’s Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
| | - Suman R. Das
- Department of Medicine, Division of Infectious Disease, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Siyuan Ma
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Jeremy A. Goettel
- Department of Pathology, Microbiology and Immunology, Division of Molecular Pathogenesis, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Seesandra V. Rajagopala
- Department of Medicine, Division of Infectious Disease, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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DeFord L, Yoon JY. Soil microbiome characterization and its future directions with biosensing. J Biol Eng 2024; 18:50. [PMID: 39256848 PMCID: PMC11389470 DOI: 10.1186/s13036-024-00444-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 08/22/2024] [Indexed: 09/12/2024] Open
Abstract
Soil microbiome characterization is typically achieved with next-generation sequencing (NGS) techniques. Metabarcoding is very common, and meta-omics is growing in popularity. These techniques have been instrumental in microbiology, but they have limitations. They require extensive time, funding, expertise, and computing power to be effective. Moreover, these techniques are restricted to controlled laboratory conditions; they are not applicable in field settings, nor can they rapidly generate data. This hinders using NGS as an environmental monitoring tool or an in-situ checking device. Biosensing technology can be applied to soil microbiome characterization to overcome these limitations and to complement NGS techniques. Biosensing has been used in biomedical applications for decades, and many successful commercial products are on the market. Given its previous success, biosensing has much to offer soil microbiome characterization. There is a great variety of biosensors and biosensing techniques, and a few in particular are better suited for soil field studies. Aptamers are more stable than enzymes or antibodies and are more ready for field-use biosensors. Given that any microbiome is complex, a multiplex sensor will be needed, and with large, complicated datasets, machine learning might benefit these analyses. If the signals from the biosensors are optical, a smartphone can be used as a portable optical reader and potential data-analyzing device. Biosensing is a rich field that couples engineering and biology, and applying its toolset to help advance soil microbiome characterization would be a boon to microbiology more broadly.
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Affiliation(s)
- Lexi DeFord
- Department of Biosystems Engineering, The University of Arizona, Tucson, AZ, 85721, USA
| | - Jeong-Yeol Yoon
- Department of Biosystems Engineering, The University of Arizona, Tucson, AZ, 85721, USA.
- Department of Biomedical Engineering, The University of Arizona, Tucson, AZ, 85721, USA.
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Reddy N, Chiwhane A, Acharya S, Kumar S, Parepalli A, Nelakuditi M. Harnessing the Power of the Gut Microbiome: A Review of Supplementation Therapies for Metabolic Syndrome. Cureus 2024; 16:e69682. [PMID: 39429422 PMCID: PMC11489520 DOI: 10.7759/cureus.69682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 09/18/2024] [Indexed: 10/22/2024] Open
Abstract
Metabolic syndrome (MetS) is a complex condition characterized by abdominal obesity, insulin resistance, dyslipidemia, and hypertension, all of which increase the risk of cardiovascular disease and type 2 diabetes. The gut microbiome plays a significant role in metabolic health, influencing digestion, immune function, and energy metabolism. When the gut microbiota becomes imbalanced due to poor diet and antibiotic use, it can lead to systemic inflammation, insulin resistance, and abnormal lipid metabolism, which are central features of MetS. This review explores the connection between gut microbial imbalances and MetS, focusing on the impact of the gut microbiome on metabolic health. Supplementation therapies targeting the gut microbiome, such as probiotics, prebiotics, synbiotics, and postbiotics, are evaluated for their potential to improve metabolic parameters in MetS patients. These interventions hold promise for enhancing insulin sensitivity, reducing inflammation, and improving lipid profiles. However, further research is needed to optimize these approaches for managing MetS. Understanding how to leverage the gut microbiome could lead to innovative, non-invasive treatments for this growing global health concern.
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Affiliation(s)
- Nikhil Reddy
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Anjalee Chiwhane
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Sourya Acharya
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Sunil Kumar
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Avinash Parepalli
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Manikanta Nelakuditi
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
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Sola F, Ayala D, Pulido M, Ayala R, López-Cerero L, Hernández I, Ruiz D. ginmappeR: an unified approach for integrating gene and protein identifiers across biological sequence databases. BIOINFORMATICS ADVANCES 2024; 4:vbae129. [PMID: 39262905 PMCID: PMC11387618 DOI: 10.1093/bioadv/vbae129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 08/09/2024] [Accepted: 08/27/2024] [Indexed: 09/13/2024]
Abstract
Summary The proliferation of biological sequence data, due to developments in molecular biology techniques, has led to the creation of numerous open access databases on gene and protein sequencing. However, the lack of direct equivalence between identifiers across these databases difficults data integration. To address this challenge, we introduce ginmappeR, an integrated R package facilitating the translation of gene and protein identifiers between databases. By providing a unified interface, ginmappeR streamlines the integration of diverse data sources into biological workflows, so it enhances efficiency and user experience. Availability and implementation from Bioconductor: https://bioconductor.org/packages/ginmappeR.
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Affiliation(s)
- Fernando Sola
- SCORE Lab, DEAL, University of Seville, ETSII, 41012 Seville, Spain
| | - Daniel Ayala
- SCORE Lab, DEAL, University of Seville, ETSII, 41012 Seville, Spain
| | - Marina Pulido
- Department of Microbiology, University of Seville, 41009 Seville, Spain
- Institute of Biomedicine of Seville, Virgen Macarena University Hospital, CSIC, University of Seville, 41013 Seville, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), 28029 Madrid, Spain
| | - Rafael Ayala
- Molecular Cryo-Electron Microscopy Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa 904-0411, Japan
| | - Lorena López-Cerero
- Department of Microbiology, University of Seville, 41009 Seville, Spain
- Institute of Biomedicine of Seville, Virgen Macarena University Hospital, CSIC, University of Seville, 41013 Seville, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), 28029 Madrid, Spain
| | - Inma Hernández
- SCORE Lab, DEAL, University of Seville, ETSII, 41012 Seville, Spain
| | - David Ruiz
- SCORE Lab, DEAL, University of Seville, ETSII, 41012 Seville, Spain
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Herrera-Quintana L, Vázquez-Lorente H, Hinojosa-Nogueira D, Plaza-Diaz J. Relationship between Infant Feeding and the Microbiome: Implications for Allergies and Food Intolerances. CHILDREN (BASEL, SWITZERLAND) 2024; 11:1030. [PMID: 39201963 PMCID: PMC11353207 DOI: 10.3390/children11081030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 08/16/2024] [Accepted: 08/20/2024] [Indexed: 09/03/2024]
Abstract
Childhood is a critical period for immune system development, which is greatly influenced by the gut microbiome. Likewise, a number of factors affect the gut microbiome composition and diversity, including breastfeeding, formula feeding, and solid foods introduction. In this regard, several studies have previously demonstrated that breastfeeding promotes a favorable microbiome. In contrast, formula feeding and the early incorporation of certain solid foods may adversely affect microbiome development. Additionally, there is increasing evidence that disruptions in the early microbiome can lead to allergic conditions and food intolerances. Thus, developing strategies to promote optimal infant nutrition requires an understanding of the relationship between infant nutrition and long-term health. The present review aims to examine the relationship between infant feeding practices and the microbiome, as well as its implications on allergies and food intolerances in infants. Moreover, this study synthesizes existing evidence on how different eating habits influence the microbiome. It highlights their implications for the prevention of allergies and food intolerances. In conclusion, introducing allergenic solid foods before six months, alongside breastfeeding, may significantly reduce allergies and food intolerances risks, being also associated with variations in gut microbiome and related complications.
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Affiliation(s)
- Lourdes Herrera-Quintana
- Department of Physiology, Schools of Pharmacy and Medicine, University of Granada, 18071 Granada, Spain; (L.H.-Q.); (H.V.-L.)
- Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain
| | - Héctor Vázquez-Lorente
- Department of Physiology, Schools of Pharmacy and Medicine, University of Granada, 18071 Granada, Spain; (L.H.-Q.); (H.V.-L.)
- Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain
| | - Daniel Hinojosa-Nogueira
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Laboratorio del Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario de Málaga (Virgen de la Victoria), 29590 Málaga, Spain;
| | - Julio Plaza-Diaz
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain
- Instituto de Investigación Biosanitaria IBS, GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
- Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada
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Sajid S, Mashkoor M, Jørgensen MG, Christensen LP, Hansen PR, Franzyk H, Mirza O, Prabhala BK. The Y-ome Conundrum: Insights into Uncharacterized Genes and Approaches for Functional Annotation. Mol Cell Biochem 2024; 479:1957-1968. [PMID: 37610616 DOI: 10.1007/s11010-023-04827-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 08/09/2023] [Indexed: 08/24/2023]
Abstract
The ever-increasing availability of genome sequencing data has revealed a substantial number of uncharacterized genes without known functions across various organisms. The first comprehensive genome sequencing of E. coli K12 revealed that more than 50% of its open reading frames corresponded to transcripts with no known functions. The group of protein-coding genes without a functional description and/or a recognized pathway, beginning with the letter "Y", is classified as the "y-ome". Several efforts have been made to elucidate the functions of these genes and to recognize their role in biological processes. This review provides a brief update on various strategies employed when studying the y-ome, such as high-throughput experimental approaches, comparative omics, metabolic engineering, gene expression analysis, and data integration techniques. Additionally, we highlight recent advancements in functional annotation methods, including the use of machine learning, network analysis, and functional genomics approaches. Novel approaches are required to produce more precise functional annotations across the genome to reduce the number of genes with unknown functions.
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Affiliation(s)
- Salvia Sajid
- Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen Ø, Denmark
- Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark
| | - Maliha Mashkoor
- Department of Surgery, Center for Surgical Sciences, Zealand University Hospital, Lykkebækvej 1, 4600, Køge, Denmark
| | - Mikkel Girke Jørgensen
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark
| | - Lars Porskjær Christensen
- Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark
| | - Paul Robert Hansen
- Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen Ø, Denmark
| | - Henrik Franzyk
- Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen Ø, Denmark
| | - Osman Mirza
- Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen Ø, Denmark
| | - Bala Krishna Prabhala
- Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark.
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Meier TA, Refahi MS, Hearne G, Restifo DS, Munoz-Acuna R, Rosen GL, Woloszynek S. The Role and Applications of Artificial Intelligence in the Treatment of Chronic Pain. Curr Pain Headache Rep 2024; 28:769-784. [PMID: 38822995 DOI: 10.1007/s11916-024-01264-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/28/2024] [Indexed: 06/03/2024]
Abstract
PURPOSE OF REVIEW This review aims to explore the interface between artificial intelligence (AI) and chronic pain, seeking to identify areas of focus for enhancing current treatments and yielding novel therapies. RECENT FINDINGS In the United States, the prevalence of chronic pain is estimated to be upwards of 40%. Its impact extends to increased healthcare costs, reduced economic productivity, and strain on healthcare resources. Addressing this condition is particularly challenging due to its complexity and the significant variability in how patients respond to treatment. Current options often struggle to provide long-term relief, with their benefits rarely outweighing the risks, such as dependency or other side effects. Currently, AI has impacted four key areas of chronic pain treatment and research: (1) predicting outcomes based on clinical information; (2) extracting features from text, specifically clinical notes; (3) modeling 'omic data to identify meaningful patient subgroups with potential for personalized treatments and improved understanding of disease processes; and (4) disentangling complex neuronal signals responsible for pain, which current therapies attempt to modulate. As AI advances, leveraging state-of-the-art architectures will be essential for improving chronic pain treatment. Current efforts aim to extract meaningful representations from complex data, paving the way for personalized medicine. The identification of unique patient subgroups should reveal targets for tailored chronic pain treatments. Moreover, enhancing current treatment approaches is achievable by gaining a more profound understanding of patient physiology and responses. This can be realized by leveraging AI on the increasing volume of data linked to chronic pain.
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Affiliation(s)
| | - Mohammad S Refahi
- Ecological and Evolutionary Signal-Processing and Informatics (EESI) Laboratory, Department of Electrical and Computer Engineering, Drexel University, Philadelphia, PA, USA
| | - Gavin Hearne
- Ecological and Evolutionary Signal-Processing and Informatics (EESI) Laboratory, Department of Electrical and Computer Engineering, Drexel University, Philadelphia, PA, USA
| | | | - Ricardo Munoz-Acuna
- Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Gail L Rosen
- Ecological and Evolutionary Signal-Processing and Informatics (EESI) Laboratory, Department of Electrical and Computer Engineering, Drexel University, Philadelphia, PA, USA
| | - Stephen Woloszynek
- Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
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Kruk ME, Mehta S, Murray K, Higgins L, Do K, Johnson JE, Wagner R, Wendt CH, O’Connor JB, Harris JK, Laguna TA, Jagtap PD, Griffin TJ. An integrated metaproteomics workflow for studying host-microbe dynamics in bronchoalveolar lavage samples applied to cystic fibrosis disease. mSystems 2024; 9:e0092923. [PMID: 38934598 PMCID: PMC11264604 DOI: 10.1128/msystems.00929-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 05/13/2024] [Indexed: 06/28/2024] Open
Abstract
Airway microbiota are known to contribute to lung diseases, such as cystic fibrosis (CF), but their contributions to pathogenesis are still unclear. To improve our understanding of host-microbe interactions, we have developed an integrated analytical and bioinformatic mass spectrometry (MS)-based metaproteomics workflow to analyze clinical bronchoalveolar lavage (BAL) samples from people with airway disease. Proteins from BAL cellular pellets were processed and pooled together in groups categorized by disease status (CF vs. non-CF) and bacterial diversity, based on previously performed small subunit rRNA sequencing data. Proteins from each pooled sample group were digested and subjected to liquid chromatography tandem mass spectrometry (MS/MS). MS/MS spectra were matched to human and bacterial peptide sequences leveraging a bioinformatic workflow using a metagenomics-guided protein sequence database and rigorous evaluation. Label-free quantification revealed differentially abundant human peptides from proteins with known roles in CF, like neutrophil elastase and collagenase, and proteins with lesser-known roles in CF, including apolipoproteins. Differentially abundant bacterial peptides were identified from known CF pathogens (e.g., Pseudomonas), as well as other taxa with potentially novel roles in CF. We used this host-microbe peptide panel for targeted parallel-reaction monitoring validation, demonstrating for the first time an MS-based assay effective for quantifying host-microbe protein dynamics within BAL cells from individual CF patients. Our integrated bioinformatic and analytical workflow combining discovery, verification, and validation should prove useful for diverse studies to characterize microbial contributors in airway diseases. Furthermore, we describe a promising preliminary panel of differentially abundant microbe and host peptide sequences for further study as potential markers of host-microbe relationships in CF disease pathogenesis.IMPORTANCEIdentifying microbial pathogenic contributors and dysregulated human responses in airway disease, such as CF, is critical to understanding disease progression and developing more effective treatments. To this end, characterizing the proteins expressed from bacterial microbes and human host cells during disease progression can provide valuable new insights. We describe here a new method to confidently detect and monitor abundance changes of both microbe and host proteins from challenging BAL samples commonly collected from CF patients. Our method uses both state-of-the art mass spectrometry-based instrumentation to detect proteins present in these samples and customized bioinformatic software tools to analyze the data and characterize detected proteins and their association with CF. We demonstrate the use of this method to characterize microbe and host proteins from individual BAL samples, paving the way for a new approach to understand molecular contributors to CF and other diseases of the airway.
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Affiliation(s)
- Monica E. Kruk
- Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minneapolis, Minnesota, USA
| | - Subina Mehta
- Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minneapolis, Minnesota, USA
| | - Kevin Murray
- Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minneapolis, Minnesota, USA
- Center for Metabolomics and Proteomics, University of Minnesota, Minneapolis, Minnesota, USA
| | - LeeAnn Higgins
- Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minneapolis, Minnesota, USA
- Center for Metabolomics and Proteomics, University of Minnesota, Minneapolis, Minnesota, USA
| | - Katherine Do
- Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minneapolis, Minnesota, USA
| | - James E. Johnson
- Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota, USA
| | - Reid Wagner
- Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota, USA
| | - Chris H. Wendt
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Medical School, University of Minnesota, Minneapolis, Minnesota, USA
- Minneapolis VA Health Care System, Minneapolis, Minnesota, USA
| | - John B. O’Connor
- Department of Pediatrics, Division of Pulmonary and Sleep Medicine, Seattle Children’s Hospital, Seattle, Washington, USA
| | - J. Kirk Harris
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Theresa A. Laguna
- Department of Pediatrics, Division of Pulmonary and Sleep Medicine, Seattle Children’s Hospital, Seattle, Washington, USA
- Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA
| | - Pratik D. Jagtap
- Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minneapolis, Minnesota, USA
| | - Timothy J. Griffin
- Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minneapolis, Minnesota, USA
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Wang A, Fekete EEF, Creskey M, Cheng K, Ning Z, Pfeifle A, Li X, Figeys D, Zhang X. Assessing fecal metaproteomics workflow and small protein recovery using DDA and DIA PASEF mass spectrometry. MICROBIOME RESEARCH REPORTS 2024; 3:39. [PMID: 39421247 PMCID: PMC11480776 DOI: 10.20517/mrr.2024.21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 06/17/2024] [Accepted: 06/25/2024] [Indexed: 10/19/2024]
Abstract
Aim: This study aims to evaluate the impact of experimental workflow on fecal metaproteomic observations, including the recovery of small and antimicrobial proteins often overlooked in metaproteomic studies. The overarching goal is to provide guidance for optimized metaproteomic experimental design, considering the emerging significance of the gut microbiome in human health, disease, and therapeutic interventions. Methods: Mouse feces were utilized as the experimental model. Fecal sample pre-processing methods (differential centrifugation and non-differential centrifugation), protein digestion techniques (in-solution and filter-aided), data acquisition modes (data-dependent and data-independent, or DDA and DIA) when combined with parallel accumulation-serial fragmentation (PASEF), and different bioinformatic workflows were assessed. Results: We showed that, in DIA-PASEF metaproteomics, the library-free search using protein sequence database generated from DDA-PASEF data achieved better identifications than using the generated spectral library. Compared to DDA, DIA-PASEF identified more microbial peptides, quantified more proteins with fewer missing values, and recovered more small antimicrobial proteins. We did not observe any obvious impacts of protein digestion methods on both taxonomic and functional profiles. However, differential centrifugation decreased the recovery of small and antimicrobial proteins, biased the taxonomic observation with a marked overestimation of Muribaculum species, and altered the measured functional compositions of metaproteome. Conclusion: This study underscores the critical impact of experimental choices on metaproteomic outcomes and sheds light on the potential biases introduced at different stages of the workflow. The comprehensive methodological comparisons serve as a valuable guide for researchers aiming to enhance the accuracy and completeness of metaproteomic analyses.
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Affiliation(s)
- Angela Wang
- Regulatory Research Division, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa K1A 0K9, Ontario, Canada
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa K1H 8M5, Ontario, Canada
- Authors contributed equally
| | - Emily E F Fekete
- Regulatory Research Division, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa K1A 0K9, Ontario, Canada
- Authors contributed equally
| | - Marybeth Creskey
- Regulatory Research Division, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa K1A 0K9, Ontario, Canada
| | - Kai Cheng
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa K1H 8M5, Ontario, Canada
- School of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa K1H 8M5, Ontario, Canada
| | - Zhibin Ning
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa K1H 8M5, Ontario, Canada
- School of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa K1H 8M5, Ontario, Canada
| | - Annabelle Pfeifle
- Regulatory Research Division, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa K1A 0K9, Ontario, Canada
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa K1H 8M5, Ontario, Canada
| | - Xuguang Li
- Regulatory Research Division, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa K1A 0K9, Ontario, Canada
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa K1H 8M5, Ontario, Canada
| | - Daniel Figeys
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa K1H 8M5, Ontario, Canada
- School of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa K1H 8M5, Ontario, Canada
| | - Xu Zhang
- Regulatory Research Division, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa K1A 0K9, Ontario, Canada
- School of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa K1H 8M5, Ontario, Canada
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Do K, Mehta S, Wagner R, Bhuming D, Rajczewski AT, Skubitz APN, Johnson JE, Griffin TJ, Jagtap PD. A novel clinical metaproteomics workflow enables bioinformatic analysis of host-microbe dynamics in disease. mSphere 2024; 9:e0079323. [PMID: 38780289 PMCID: PMC11332332 DOI: 10.1128/msphere.00793-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 04/17/2024] [Indexed: 05/25/2024] Open
Abstract
Clinical metaproteomics has the potential to offer insights into the host-microbiome interactions underlying diseases. However, the field faces challenges in characterizing microbial proteins found in clinical samples, usually present at low abundance relative to the host proteins. As a solution, we have developed an integrated workflow coupling mass spectrometry-based analysis with customized bioinformatic identification, quantification, and prioritization of microbial proteins, enabling targeted assay development to investigate host-microbe dynamics in disease. The bioinformatics tools are implemented in the Galaxy ecosystem, offering the development and dissemination of complex bioinformatic workflows. The modular workflow integrates MetaNovo (to generate a reduced protein database), SearchGUI/PeptideShaker and MaxQuant [to generate peptide-spectral matches (PSMs) and quantification], PepQuery2 (to verify the quality of PSMs), Unipept (for taxonomic and functional annotation), and MSstatsTMT (for statistical analysis). We have utilized this workflow in diverse clinical samples, from the characterization of nasopharyngeal swab samples to bronchoalveolar lavage fluid. Here, we demonstrate its effectiveness via analysis of residual fluid from cervical swabs. The complete workflow, including training data and documentation, is available via the Galaxy Training Network, empowering non-expert researchers to utilize these powerful tools in their clinical studies. IMPORTANCE Clinical metaproteomics has immense potential to offer functional insights into the microbiome and its contributions to human disease. However, there are numerous challenges in the metaproteomic analysis of clinical samples, including handling of very large protein sequence databases for sensitive and accurate peptide and protein identification from mass spectrometry data, as well as taxonomic and functional annotation of quantified peptides and proteins to enable interpretation of results. To address these challenges, we have developed a novel clinical metaproteomics workflow that provides customized bioinformatic identification, verification, quantification, and taxonomic and functional annotation. This bioinformatic workflow is implemented in the Galaxy ecosystem and has been used to characterize diverse clinical sample types, such as nasopharyngeal swabs and bronchoalveolar lavage fluid. Here, we demonstrate its effectiveness and availability for use by the research community via analysis of residual fluid from cervical swabs.
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Affiliation(s)
- Katherine Do
- Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA
| | - Subina Mehta
- Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA
| | - Reid Wagner
- Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota, USA
| | - Dechen Bhuming
- Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA
| | - Andrew T. Rajczewski
- Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA
| | - Amy P. N. Skubitz
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA
| | - James E. Johnson
- Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota, USA
| | - Timothy J. Griffin
- Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA
| | - Pratik D. Jagtap
- Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA
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Hu L, Sun L, Yang C, Zhang DW, Wei YY, Yang MM, Wu HM, Fei GH. Gut microbiota-derived acetate attenuates lung injury induced by influenza infection via protecting airway tight junctions. J Transl Med 2024; 22:570. [PMID: 38879538 PMCID: PMC11179378 DOI: 10.1186/s12967-024-05376-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 06/06/2024] [Indexed: 06/19/2024] Open
Abstract
BACKGROUND Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host's response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown. METHODS A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA). RESULTS IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1β). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner. CONCLUSION Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.
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Affiliation(s)
- Lei Hu
- Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, China
- Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, China
| | - Li Sun
- Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, China
- Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, China
| | - Chun Yang
- Department of Emergency Intensive Care Unit, First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Da-Wei Zhang
- Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, China
- Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, China
| | - Yuan-Yuan Wei
- Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, China
- Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, China
| | - Ming-Ming Yang
- Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, China
- Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, China
| | - Hui-Mei Wu
- Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, China
- Department of Geriatric Respiratory and Critical Care Medicine, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Guang-He Fei
- Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, China.
- Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, China.
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Xu MQ, Pan F, Peng LH, Yang YS. Advances in the isolation, cultivation, and identification of gut microbes. Mil Med Res 2024; 11:34. [PMID: 38831462 PMCID: PMC11145792 DOI: 10.1186/s40779-024-00534-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 04/17/2024] [Indexed: 06/05/2024] Open
Abstract
The gut microbiome is closely associated with human health and the development of diseases. Isolating, characterizing, and identifying gut microbes are crucial for research on the gut microbiome and essential for advancing our understanding and utilization of it. Although culture-independent approaches have been developed, a pure culture is required for in-depth analysis of disease mechanisms and the development of biotherapy strategies. Currently, microbiome research faces the challenge of expanding the existing database of culturable gut microbiota and rapidly isolating target microorganisms. This review examines the advancements in gut microbe isolation and cultivation techniques, such as culturomics, droplet microfluidics, phenotypic and genomics selection, and membrane diffusion. Furthermore, we evaluate the progress made in technology for identifying gut microbes considering both non-targeted and targeted strategies. The focus of future research in gut microbial culturomics is expected to be on high-throughput, automation, and integration. Advancements in this field may facilitate strain-level investigation into the mechanisms underlying diseases related to gut microbiota.
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Affiliation(s)
- Meng-Qi Xu
- Department of Gastroenterology and Hepatology, the First Medical Center of Chinese, PLA General Hospital, Beijing, 100853, China
- Medical School of Chinese PLA, Beijing, 100853, China
| | - Fei Pan
- Department of Gastroenterology and Hepatology, the First Medical Center of Chinese, PLA General Hospital, Beijing, 100853, China
| | - Li-Hua Peng
- Department of Gastroenterology and Hepatology, the First Medical Center of Chinese, PLA General Hospital, Beijing, 100853, China
| | - Yun-Sheng Yang
- Department of Gastroenterology and Hepatology, the First Medical Center of Chinese, PLA General Hospital, Beijing, 100853, China.
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Shinde DB, Mahore JG, Giram PS, Singh SL, Sharda A, Choyan D, Musale S. Microbiota of Saliva: A Non-invasive Diagnostic Tool. Indian J Microbiol 2024; 64:328-342. [PMID: 39010986 PMCID: PMC11246313 DOI: 10.1007/s12088-024-01219-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 01/30/2024] [Indexed: 07/17/2024] Open
Abstract
Potential of salivary microbiota as a non-invasive diagnostic tool for various diseases are explained in the present review. Traditional diagnostic methods rely on blood, which has limitations in terms of collection and biomarker specificity. We discuss the concept of normal flora and how disruptions in oral microbiota can be indicative of diseases. Saliva, harboring a diverse microbial community, offers promise as a diagnostic biomarker source for oral and non-oral conditions. We delve into the role of microbial dysbiosis in disease pathogenesis and the prospects of using biological indicators like dysbiosis for diagnosis, prediction, and monitoring. This review also emphasizes the significance of saliva microbiota in advancing early disease detection and timely intervention. We addressed the following research question and objectives: Can the microbiota of saliva serve as a non-invasive diagnostic tool for the early detection and monitoring of both oral and non-oral diseases? To achieve this, we will explore the normal flora of microorganisms in the oral cavity, the impact of microbial dysbiosis, and the potential of using specific pathogenic microorganisms as biomarkers. Additionally, we will investigate the correlation between oral and non-oral diseases by analyzing total saliva or site-specific dental biofilms for signs of symbiosis or dysbiosis. This research seeks to contribute valuable insights into the development of a non-invasive diagnostic approach with broad applications in healthcare.
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Affiliation(s)
- Dasharath B Shinde
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University), Pune, 412115 India
| | - Jayashri G Mahore
- Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, 411018 India
- Sinhgad College of Pharmacy, Vadgaon (Bk.), Pune, 411041 India
| | - Prabhanjan S Giram
- Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, 411018 India
- Department of Pharmaceutical Sciences, The State University of New York, Buffalo, NY 14214 USA
| | - Shaktikumar L Singh
- Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, 411018 India
| | - Aditi Sharda
- Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, 411018 India
| | - Divya Choyan
- Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, 411018 India
| | - Shubham Musale
- Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, 411018 India
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Porcari S, Fusco W, Spivak I, Fiorani M, Gasbarrini A, Elinav E, Cammarota G, Ianiro G. Fine-tuning the gut ecosystem: the current landscape and outlook of artificial microbiome therapeutics. Lancet Gastroenterol Hepatol 2024; 9:460-475. [PMID: 38604200 DOI: 10.1016/s2468-1253(23)00357-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 10/04/2023] [Accepted: 10/10/2023] [Indexed: 04/13/2024]
Abstract
The gut microbiome is acknowledged as a key determinant of human health, and technological progress in the past two decades has enabled the deciphering of its composition and functions and its role in human disorders. Therefore, manipulation of the gut microbiome has emerged as a promising therapeutic option for communicable and non-communicable disorders. Full exploitation of current therapeutic microbiome modulators (including probiotics, prebiotics, and faecal microbiota transplantation) is hindered by several factors, including poor precision, regulatory and safety issues, and the impossibility of providing reproducible and targeted treatments. Artificial microbiota therapeutics (which include a wide range of products, such as microbiota consortia, bacteriophages, bacterial metabolites, and engineered probiotics) have appeared as an evolution of current microbiota modulators, as they promise safe and reproducible effects, with variable levels of precision via different pathways. We describe the landscape of artificial microbiome therapeutics, from those already on the market to those still in the pipeline, and outline the major challenges for positioning these therapeutics in clinical practice.
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Affiliation(s)
- Serena Porcari
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; UOC Gastroenterologia and UOC CEMAD Medicina Interna e Gastroenterologia, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - William Fusco
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; UOC Gastroenterologia and UOC CEMAD Medicina Interna e Gastroenterologia, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Igor Spivak
- Systems Immunology Department, Weizmann Institute of Science, Rehovot, Israel; Medical Clinic III, University Hospital Aachen, Aachen, Germany
| | - Marcello Fiorani
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; UOC Gastroenterologia and UOC CEMAD Medicina Interna e Gastroenterologia, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; UOC Gastroenterologia and UOC CEMAD Medicina Interna e Gastroenterologia, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Eran Elinav
- Systems Immunology Department, Weizmann Institute of Science, Rehovot, Israel; Microbiome and Cancer Division, DKFZ, Heidelberg, Germany
| | - Giovanni Cammarota
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; UOC Gastroenterologia and UOC CEMAD Medicina Interna e Gastroenterologia, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Gianluca Ianiro
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; UOC Gastroenterologia and UOC CEMAD Medicina Interna e Gastroenterologia, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
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Liu D, Xie LS, Lian S, Li K, Yang Y, Wang WZ, Hu S, Liu SJ, Liu C, He Z. Anaerostipes hadrus, a butyrate-producing bacterium capable of metabolizing 5-fluorouracil. mSphere 2024; 9:e0081623. [PMID: 38470044 PMCID: PMC11036815 DOI: 10.1128/msphere.00816-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 02/22/2024] [Indexed: 03/13/2024] Open
Abstract
Anaerostipes hadrus (A. hadrus) is a dominant species in the human gut microbiota and considered a beneficial bacterium for producing probiotic butyrate. However, recent studies have suggested that A. hadrus may negatively affect the host through synthesizing fatty acid and metabolizing the anticancer drug 5-fluorouracil, indicating that the impact of A. hadrus is complex and unclear. Therefore, comprehensive genomic studies on A. hadrus need to be performed. We integrated 527 high-quality public A. hadrus genomes and five distinct metagenomic cohorts. We analyzed these data using the approaches of comparative genomics, metagenomics, and protein structure prediction. We also performed validations with culture-based in vitro assays. We constructed the first large-scale pan-genome of A. hadrus (n = 527) and identified 5-fluorouracil metabolism genes as ubiquitous in A. hadrus genomes as butyrate-producing genes. Metagenomic analysis revealed the wide and stable distribution of A. hadrus in healthy individuals, patients with inflammatory bowel disease, and patients with colorectal cancer, with healthy individuals carrying more A. hadrus. The predicted high-quality protein structure indicated that A. hadrus might metabolize 5-fluorouracil by producing bacterial dihydropyrimidine dehydrogenase (encoded by the preTA operon). Through in vitro assays, we validated the short-chain fatty acid production and 5-fluorouracil metabolism abilities of A. hadrus. We observed for the first time that A. hadrus can convert 5-fluorouracil to α-fluoro-β-ureidopropionic acid, which may result from the combined action of the preTA operon and adjacent hydA (encoding bacterial dihydropyrimidinase). Our results offer novel understandings of A. hadrus, exceptionally functional features, and potential applications. IMPORTANCE This work provides new insights into the evolutionary relationships, functional characteristics, prevalence, and potential applications of Anaerostipes hadrus.
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Affiliation(s)
- Danping Liu
- School of Engineering Medicine, Beihang University, Beijing, China
- Key Laboratory of Big Data-Based Precision Medicine, Beihang University, Ministry of Industry and Information Technology of the People’s Republic of China, Beijing, China
- Key Laboratory of Biomechanics and Mechanobiology, Beihang University, Ministry of Education, Beijing, China
| | - Li-Sheng Xie
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China
| | - Shitao Lian
- School of Engineering Medicine, Beihang University, Beijing, China
- Key Laboratory of Big Data-Based Precision Medicine, Beihang University, Ministry of Industry and Information Technology of the People’s Republic of China, Beijing, China
- Key Laboratory of Biomechanics and Mechanobiology, Beihang University, Ministry of Education, Beijing, China
| | - Kexin Li
- Systems Biology and Bioinformatics (SBI), Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute (HKI), Jena, Germany
| | - Yun Yang
- School of Engineering Medicine, Beihang University, Beijing, China
- Key Laboratory of Big Data-Based Precision Medicine, Beihang University, Ministry of Industry and Information Technology of the People’s Republic of China, Beijing, China
- Key Laboratory of Biomechanics and Mechanobiology, Beihang University, Ministry of Education, Beijing, China
| | - Wen-Zhao Wang
- State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
| | - Songnian Hu
- State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
| | - Shuang-Jiang Liu
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China
- State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
| | - Chang Liu
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China
| | - Zilong He
- School of Engineering Medicine, Beihang University, Beijing, China
- Key Laboratory of Big Data-Based Precision Medicine, Beihang University, Ministry of Industry and Information Technology of the People’s Republic of China, Beijing, China
- Key Laboratory of Biomechanics and Mechanobiology, Beihang University, Ministry of Education, Beijing, China
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