|
1
|
Dai S, Long J, Han W, Zhang L, Chen B. Alleviative effect of probiotics and prebiotics on dry eye in type 2 diabetic mice through the gut-eye axis. Ocul Surf 2025; 36:244-260. [PMID: 39922458 DOI: 10.1016/j.jtos.2025.02.004] [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: 10/11/2024] [Revised: 02/05/2025] [Accepted: 02/05/2025] [Indexed: 02/10/2025]
Abstract
Diabetes Mellitus (DM) is a metabolic disease that manifests as a state of "chronic low-grade inflammation". Patients with DM have a disorder of intestinal flora. There is a discernible correlation between this disorder of intestinal flora and the onset and progression of eye diseases, which offers novel insights into treating eye diseases through the modulation of intestinal flora. Here, we demonstrated that a high-fat diet and streptozotocin injection-induced intestinal microbiota dysbiosis can lead to dry eye-like manifestations in T2DM mice. Probiotic and prebiotic treatments not only alleviated intestinal inflammation and barrier disruption, but also mitigated damage to the lacrimal barrier and suppressed immune cell infiltration and inflammatory responses. Additional mechanism investigation found that probiotics and prebiotics inhibited the TLR4/NF-κB signaling pathway and its downstream pro-inflammatory products both in the lacrimal gland and colon. 16S RNA sequencing identified a reduction in the bacterial genera Akkermansia and Lactobacillus in the fecal samples of DM mice. By contrast, treatment with probiotics and prebiotics led to a reshaping of the intestinal microbial community and a reduction in bile acid metabolites, such as taurocholic acid and deoxycholic acid. Our current study demonstrates that probiotic and prebiotic treatments can ameliorate dry eye-like symptoms and associated pathological changes in T2DM mice. Moreover, we proved that a high-fat diet and STZ-induced microbiota dysbiosis were involved in diabetic dry eye through the gut-eye axis.
Collapse
Affiliation(s)
- Shirui Dai
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, 410011, China.
| | - Jianfeng Long
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, 410011, China.
| | - Wentao Han
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, 410011, China.
| | - Liwei Zhang
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, 410011, China.
| | - Baihua Chen
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, 410011, China.
| |
Collapse
|
|
2
|
Stefanis C, Tsigalou C, Bezirtzoglou I, Voidarou C(C, Stavropoulou E. Microbiome Research in Greece: A Comprehensive Bibliometric Study. Microorganisms 2025; 13:725. [PMID: 40284562 PMCID: PMC12029916 DOI: 10.3390/microorganisms13040725] [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: 02/06/2025] [Revised: 03/18/2025] [Accepted: 03/20/2025] [Indexed: 04/29/2025] Open
Abstract
Bibliometric analyses are increasingly used to evaluate scientific domains, revealing research trends, productivity, and impact. This study provides a bibliometric analysis of microbiome-related research conducted by Greek scientists. Data were retrieved from the Scopus database, using the keyword "microbiome" (English) for publications until December 2024. Bibliometric analysis was performed using VOSviewer and the bibliometrix package in R. Our findings indicate that research output has increased exponentially since 2018, with the National and Kapodistrian University of Athens and the Aristotle University of Thessaloniki leading microbiome research in Greece. Medicine, biochemistry, genetics, molecular biology, immunology, and microbiology are the predominant research fields. The keyword analysis highlights "microbiome", "microbiota", "probiotics", "prebiotics", "intestinal flora", and "16S rRNA" as central topics. Additionally, we acknowledge the role played by alternative microbial markers, including 18S rRNA/ITS sequencing, for fungal diversity studies. This bibliometric study demonstrates a dynamic and evolving research landscape in Greece and highlights the international relevance of Greek contributions to microbiome science.
Collapse
Affiliation(s)
- Christos Stefanis
- Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (C.T.); (E.S.)
| | - Christina Tsigalou
- Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (C.T.); (E.S.)
| | | | | | - Elisavet Stavropoulou
- Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (C.T.); (E.S.)
| |
Collapse
|
|
3
|
Chong S, Lin M, Chong D, Jensen S, Lau NS. A systematic review on gut microbiota in type 2 diabetes mellitus. Front Endocrinol (Lausanne) 2025; 15:1486793. [PMID: 39897957 PMCID: PMC11782031 DOI: 10.3389/fendo.2024.1486793] [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: 08/26/2024] [Accepted: 12/18/2024] [Indexed: 02/04/2025] Open
Abstract
Aims/hypothesis The gut microbiota play crucial roles in the digestion and degradation of nutrients, synthesis of biological agents, development of the immune system, and maintenance of gastrointestinal integrity. Gut dysbiosis is thought to be associated with type 2 diabetes mellitus (T2DM), one of the world's fastest growing diseases. The aim of this systematic review is to identify differences in the composition and diversity of the gut microbiota in individuals with T2DM. Methods A systematic search was conducted to identify studies reporting on the difference in gut microbiota composition between individuals with T2DM and healthy controls. Relevant studies were evaluated, and their characteristics and results were extracted using a standardized data extraction form. The studies were assessed for risk of bias and their findings were reported narratively. Results 58 observational studies published between 2010 and 2024 were included. Beta diversity was commonly reported to be different between individuals with T2DM and healthy individuals. Genera Lactobacillus, Escherichia-Shigella, Enterococcus, Subdoligranulum and Fusobacteria were found to be positively associated; while Akkermansia, Bifidobacterium, Bacteroides, Roseburia, Faecalibacteirum and Prevotella were found to be negatively associated with T2DM. Conclusions This systematic review demonstrates a strong association between T2DM and gut dysbiosis, as evidenced by differential microbial abundances and altered diversity indices. Among these taxa, Escherichia-Shigella is consistently associated with T2DM, whereas Faecalibacterium prausnitzii appears to offer a protective effect against T2DM. However, the heterogeneity and observational nature of these studies preclude the establishment of causative relationships. Future research should incorporate age, diet and medication-matched controls, and include functional analysis of these gut microbes. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42023459937.
Collapse
Affiliation(s)
- Serena Chong
- South West Sydney Limb Preservation and Wound Research, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
- South West Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Mike Lin
- Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Garvan Institute of Research, Sydney, NSW, Australia
| | - Deborah Chong
- Animal Health Laboratory, Department of Natural Resources and Environment Tasmania, Tasmania, TAS, Australia
| | - Slade Jensen
- South West Sydney Limb Preservation and Wound Research, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
- Infectious Disease and Microbiology, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
- School of Medicine Antibiotic Resistance and Mobile Elements Groups, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
| | - Namson S. Lau
- South West Sydney Limb Preservation and Wound Research, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
- South West Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
- Liverpool Diabetes Collaboration, Ingham Institute of Applied Medical Research, Sydney, NSW, Australia
| |
Collapse
|
|
4
|
Martínez-Carrillo BE, De Sales-Millán A, Aguirre-Garrido JF, Valdés-Ramos R, de María Cruz-Estrada F, Castillo-Cardiel JA. Changes in the Composition and Diversity of the Intestinal Microbiota Associated with Carbohydrate Consumption in Type 2 Diabetes Mellitus Patients. Int J Mol Sci 2024; 25:12359. [PMID: 39596424 PMCID: PMC11594722 DOI: 10.3390/ijms252212359] [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: 10/09/2024] [Revised: 11/02/2024] [Accepted: 11/11/2024] [Indexed: 11/28/2024] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a multifactorial disease, influenced by dietary and environmental factors that can modify the intestinal microbiota. The aim of this study was to evaluate changes in the composition and diversity of the intestinal microbiota associated with carbohydrate (CHO) consumption in T2DM patients. Forty patients participated, with and without T2DM. Fecal samples were collected for the characterization of microbial diversity from the massive sequencing of the 16S rRNA gene. Carbohydrate consumption was quantified using the Frequency Consumption Foods questionnaire (FCF), the groups were categorized according to Body Mass Index (BMI) and BMI + CHO consumption. The group without T2DM showed normal biochemical and anthropometric parameters, although they had a high carbohydrate consumption compared to the group with T2DM. At the phylum level, there were differences in relative abundance; the control overweight group (CL-OW > CHO) and T2DM-Normal Weight > CHO patients had increased Bacteroides and decreased Firmicutes. In contrast, the CL-OW > CHO and T2DM-OW < CHO patients, showed reduced Bacteroidetes and an elevated amount of Firmicutes. At the genus level, the differences were in the relative abundance of Roseburia, Clostridium_IV, Prevotella, and Sporobacter, associated with the consumption of carbohydrates. The groups that consumed high amounts of carbohydrates, regardless of whether they had diabetes mellitus or were overweight, had a significantly reduced proportion of Faecalibacterium, an altered proportion of Bacteroides. The high consumption of carbohydrates showed considerable modifications in the composition and diversity of the bacterial communities.
Collapse
Affiliation(s)
- Beatriz Elina Martínez-Carrillo
- Laboratorio de Investigación en Nutrición, Facultad de Medicina, Universidad Autónoma del Estado de México, Toluca 50180, Mexico; (A.D.S.-M.); (R.V.-R.); (F.d.M.C.-E.)
| | - Amapola De Sales-Millán
- Laboratorio de Investigación en Nutrición, Facultad de Medicina, Universidad Autónoma del Estado de México, Toluca 50180, Mexico; (A.D.S.-M.); (R.V.-R.); (F.d.M.C.-E.)
| | | | - Roxana Valdés-Ramos
- Laboratorio de Investigación en Nutrición, Facultad de Medicina, Universidad Autónoma del Estado de México, Toluca 50180, Mexico; (A.D.S.-M.); (R.V.-R.); (F.d.M.C.-E.)
| | - Flor de María Cruz-Estrada
- Laboratorio de Investigación en Nutrición, Facultad de Medicina, Universidad Autónoma del Estado de México, Toluca 50180, Mexico; (A.D.S.-M.); (R.V.-R.); (F.d.M.C.-E.)
| | - José Arturo Castillo-Cardiel
- Department of Research, Continuing Education and Distance Learning, Universidad Autónoma de Durango, Durango 34209, Mexico;
| |
Collapse
|
|
5
|
Zhou B, Wang C, Putzel G, Hu J, Liu M, Wu F, Chen Y, Pironti A, Li H. An integrated strain-level analytic pipeline utilizing longitudinal metagenomic data. Microbiol Spectr 2024; 12:e0143124. [PMID: 39311770 PMCID: PMC11542597 DOI: 10.1128/spectrum.01431-24] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Accepted: 08/28/2024] [Indexed: 11/08/2024] Open
Abstract
With the development of sequencing technology and analytic tools, studying within-species variations enhances the understanding of microbial biological processes. Nevertheless, most existing methods designed for strain-level analysis lack the capability to concurrently assess both strain proportions and genome-wide single nucleotide variants (SNVs) across longitudinal metagenomic samples. In this study, we introduce LongStrain, an integrated pipeline for the analysis of large-scale metagenomic data from individuals with longitudinal or repeated samples. In LongStrain, we first utilize two efficient tools, Kraken2 and Bowtie2, for the taxonomic classification and alignment of sequencing reads, respectively. Subsequently, we propose to jointly model strain proportions and shared haplotypes across samples within individuals. This approach specifically targets tracking a primary strain and a secondary strain for each subject, providing their respective proportions and SNVs as output. With extensive simulation studies of a microbial community and single species, our results demonstrate that LongStrain is superior to two genotyping methods and two deconvolution methods across a majority of scenarios. Furthermore, we illustrate the potential applications of LongStrain in the real data analysis of The Environmental Determinants of Diabetes in the Young study and a gastric intestinal metaplasia microbiome study. In summary, the proposed analytic pipeline demonstrates marked statistical efficiency over the same type of methods and has great potential in understanding the genomic variants and dynamic changes at strain level. LongStrain and its tutorial are freely available online at https://github.com/BoyanZhou/LongStrain. IMPORTANCE The advancement in DNA-sequencing technology has enabled the high-resolution identification of microorganisms in microbial communities. Since different microbial strains within species may contain extreme phenotypic variability (e.g., nutrition metabolism, antibiotic resistance, and pathogen virulence), investigating within-species variations holds great scientific promise in understanding the underlying mechanism of microbial biological processes. To fully utilize the shared genomic variants across longitudinal metagenomics samples collected in microbiome studies, we develop an integrated analytic pipeline (LongStrain) for longitudinal metagenomics data. It concurrently leverages the information on proportions of mapped reads for individual strains and genome-wide SNVs to enhance the efficiency and accuracy of strain identification. Our method helps to understand strains' dynamic changes and their association with genome-wide variants. Given the fast-growing longitudinal studies of microbial communities, LongStrain which streamlines analyses of large-scale raw sequencing data should be of great value in microbiome research communities.
Collapse
Affiliation(s)
- Boyan Zhou
- Division of
Biostatistics, Department of Population Health, New York University
School of Medicine, New
York, New York, USA
| | - Chan Wang
- Division of
Biostatistics, Department of Population Health, New York University
School of Medicine, New
York, New York, USA
| | - Gregory Putzel
- Department of
Microbiology, New York University School of
Medicine, New York, New
York, USA
| | - Jiyuan Hu
- Division of
Biostatistics, Department of Population Health, New York University
School of Medicine, New
York, New York, USA
| | - Menghan Liu
- Department of
Biological Sciences, Columbia University in the City of New
York, New York, New
York, USA
| | - Fen Wu
- Division of
Epidemiology, Department of Population Health, New York University
School of Medicine, New
York, New York, USA
| | - Yu Chen
- Division of
Epidemiology, Department of Population Health, New York University
School of Medicine, New
York, New York, USA
| | - Alejandro Pironti
- Department of
Microbiology, New York University School of
Medicine, New York, New
York, USA
| | - Huilin Li
- Division of
Biostatistics, Department of Population Health, New York University
School of Medicine, New
York, New York, USA
| |
Collapse
|
|
6
|
Huang P, Zhu Y, Qin J. Research advances in understanding crosstalk between organs and pancreatic β-cell dysfunction. Diabetes Obes Metab 2024; 26:4147-4164. [PMID: 39044309 DOI: 10.1111/dom.15787] [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: 06/18/2024] [Revised: 06/25/2024] [Accepted: 06/26/2024] [Indexed: 07/25/2024]
Abstract
Obesity has increased dramatically worldwide. Being overweight or obese can lead to various conditions, including dyslipidaemia, hypertension, glucose intolerance and metabolic syndrome (MetS), which may further lead to type 2 diabetes mellitus (T2DM). Previous studies have identified a link between β-cell dysfunction and the severity of MetS, with multiple organs and tissues affected. Identifying the associations between pancreatic β-cell dysfunction and organs is critical. Research has focused on the interaction between the liver, gut and pancreatic β-cells. However, the mechanisms and related core targets are still not perfectly elucidated. The aims of this review were to summarize the mechanisms of β-cell dysfunction and to explore the potential pathogenic pathways and targets that connect the liver, gut, adipose tissue, muscle, and brain to pancreatic β-cell dysfunction.
Collapse
Affiliation(s)
- Peng Huang
- Department of Traditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Yunling Zhu
- Department of Traditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Jian Qin
- Department of Traditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| |
Collapse
|
|
7
|
Zikou E, Koliaki C, Makrilakis K. The Role of Fecal Microbiota Transplantation (FMT) in the Management of Metabolic Diseases in Humans: A Narrative Review. Biomedicines 2024; 12:1871. [PMID: 39200335 PMCID: PMC11352194 DOI: 10.3390/biomedicines12081871] [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: 08/02/2024] [Revised: 08/12/2024] [Accepted: 08/13/2024] [Indexed: 09/02/2024] Open
Abstract
The gut microbiota represents a complex ecosystem of trillions of microorganisms residing in the human gastrointestinal tract, which is known to interact with the host physiology and regulate multiple functions. Alterations in gut microbial composition, diversity, and function are referred to as dysbiosis. Dysbiosis has been associated with a variety of chronic diseases, including Clostridioides difficile infections, but also cardiometabolic diseases, including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). The implication of gut microbiota dysbiosis in the pathogenesis of both obesity and T2DM has paved the way to implementing novel therapeutic approaches for metabolic diseases through gut microbial reconfiguration. These interventions include probiotics, prebiotics, and synbiotics, while a more innovative approach has been fecal microbiota transplantation (FMT). FMT is a procedure that delivers healthy human donor stool to another individual through the gastrointestinal tract, aiming to restore gut microbiota balance. Several studies have investigated this approach as a potential tool to mitigate the adverse metabolic effects of gut microbiota aberrations associated with obesity and T2DM. The aim of the present review was to critically summarize the existing evidence regarding the clinical applications of FMT in the management of obesity and T2DM and provide an update on the potential of this method to remodel the entire host microbiota, leading thus to weight loss and sustained metabolic benefits. Safety issues, long-term efficacy, limitations, and pitfalls associated with FMT studies are further discussed, emphasizing the need for further research and standardization in certain methodological aspects in order to optimize metabolic outcomes.
Collapse
|
|
8
|
Francis D, Sun F. A comparative analysis of mutual information methods for pairwise relationship detection in metagenomic data. BMC Bioinformatics 2024; 25:266. [PMID: 39143554 PMCID: PMC11323399 DOI: 10.1186/s12859-024-05883-7] [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: 08/02/2023] [Accepted: 07/29/2024] [Indexed: 08/16/2024] Open
Abstract
BACKGROUND Construction of co-occurrence networks in metagenomic data often employs correlation to infer pairwise relationships between microbes. However, biological systems are complex and often display qualities non-linear in nature. Therefore, the reliance on correlation alone may overlook important relationships and fail to capture the full breadth of intricacies presented in underlying interaction networks. It is of interest to incorporate metrics that are not only robust in detecting linear relationships, but non-linear ones as well. RESULTS In this paper, we explore the use of various mutual information (MI) estimation approaches for quantifying pairwise relationships in biological data and compare their performances against two traditional measures-Pearson's correlation coefficient, r, and Spearman's rank correlation coefficient, ρ. Metrics are tested on both simulated data designed to mimic pairwise relationships that may be found in ecological systems and real data from a previous study on C. diff infection. The results demonstrate that, in the case of asymmetric relationships, mutual information estimators can provide better detection ability than Pearson's or Spearman's correlation coefficients. Specifically, we find that these estimators have elevated performances in the detection of exploitative relationships, demonstrating the potential benefit of including them in future metagenomic studies. CONCLUSIONS Mutual information (MI) can uncover complex pairwise relationships in biological data that may be missed by traditional measures of association. The inclusion of such relationships when constructing co-occurrence networks can result in a more comprehensive analysis than the use of correlation alone.
Collapse
Affiliation(s)
- Dallace Francis
- Quantitative and Computational Biology Department, University of Southern California, Los Angeles, CA, 90089, USA.
| | - Fengzhu Sun
- Quantitative and Computational Biology Department, University of Southern California, Los Angeles, CA, 90089, USA
| |
Collapse
|
|
9
|
Bui TPN. The Human Microbiome as a Therapeutic Target for Metabolic Diseases. Nutrients 2024; 16:2322. [PMID: 39064765 PMCID: PMC11280041 DOI: 10.3390/nu16142322] [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: 06/21/2024] [Revised: 07/17/2024] [Accepted: 07/18/2024] [Indexed: 07/28/2024] Open
Abstract
The human microbiome functions as a separate organ in a symbiotic relationship with the host. Disruption of this host-microbe symbiosis can lead to serious health problems. Modifications to the composition and function of the microbiome have been linked to changes in host metabolic outcomes. Industrial lifestyles with high consumption of processed foods, alcoholic beverages and antibiotic use have significantly altered the gut microbiome in unfavorable ways. Therefore, understanding the causal relationship between the human microbiome and host metabolism will provide important insights into how we can better intervene in metabolic health. In this review, I will discuss the potential use of the human microbiome as a therapeutic target to improve host metabolism.
Collapse
Affiliation(s)
- Thi Phuong Nam Bui
- Department of Experimental Vascular Medicine, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands
| |
Collapse
|
|
10
|
Vallianou NG, Kounatidis D, Psallida S, Panagopoulos F, Stratigou T, Geladari E, Karampela I, Tsilingiris D, Dalamaga M. The Interplay Between Dietary Choline and Cardiometabolic Disorders: A Review of Current Evidence. Curr Nutr Rep 2024; 13:152-165. [PMID: 38427291 PMCID: PMC11133147 DOI: 10.1007/s13668-024-00521-3] [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] [Accepted: 02/13/2024] [Indexed: 03/02/2024]
Abstract
PURPOSE OF REVIEW Choline is an essential nutrient for human health and cellular homeostasis as it is necessary for the synthesis of lipid cell membranes, lipoproteins, and the synthesis of the neurotransmitter acetylcholine. The aim of this review is to analyze the beneficial effects of choline and its significance in cellular metabolism and various inflammatory pathways, such as the inflammasome. We will discuss the significance of dietary choline in cardiometabolic disorders, such as non-alcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD), and chronic kidney disease (CKD) as well as in cognitive function and associated neuropsychiatric disorders. RECENT FINDINGS Choline deficiency has been related to the development of NAFLD and cognitive disability in the offspring as well as in adulthood. In sharp contrast, excess dietary intake of choline mediated via the increased production of trimethylamine by the gut microbiota and increased trimethylamine-N-oxide (TMAO) levels has been related to atherosclerosis in most studies. In this context, CVD and CKD through the accumulation of TMAO, p-Cresyl-sulfate (pCS), and indoxyl-sulfate (IS) in serum may be the result of the interplay between excess dietary choline, the increased production of TMAO by the gut microbiota, and the resulting activation of inflammatory responses and fibrosis. A balanced diet, with no excess nor any deficiency in dietary choline, is of outmost importance regarding the prevention of cardiometabolic disorders as well as cognitive function. Large-scale studies with the use of next-generation probiotics, especially Akkermansia muciniphila and Faecalibacterium prausnitzii, should further examine their therapeutic potential in this context.
Collapse
Affiliation(s)
- Natalia G Vallianou
- Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou str, Athens, Greece.
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias str, Athens, Greece.
| | - Dimitris Kounatidis
- Department of Internal Medicine, Hippokration General Hospital, 114 Vassilissis Sofias str, Athens, Greece
| | - Sotiria Psallida
- Department of Microbiology, KAT General Hospital of Attica, 2 Nikis str, Athens, Greece
| | - Fotis Panagopoulos
- Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou str, Athens, Greece
| | - Theodora Stratigou
- Department of Endocrinology and Metabolism, Evangelismos General Hospital, 45-47 Ipsilantou str, Athens, Greece
| | - Eleni Geladari
- Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou str, Athens, Greece
| | - Irene Karampela
- 2nd Department of Critical Care, Medical School, University of Athens, Attikon General University Hospital, 1 Rimini str, Athens, Greece
| | - Dimitrios Tsilingiris
- First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Dragana, 68100, Alexandroupoli, Greece
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias str, Athens, Greece.
| |
Collapse
|
|
11
|
Sadeghi M, Mestivier D, Sobhani I. Contribution of pks+ Escherichia coli ( E. coli) to Colon Carcinogenesis. Microorganisms 2024; 12:1111. [PMID: 38930493 PMCID: PMC11205849 DOI: 10.3390/microorganisms12061111] [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: 05/21/2024] [Revised: 05/24/2024] [Accepted: 05/29/2024] [Indexed: 06/28/2024] Open
Abstract
Colorectal cancer (CRC) stands as a significant global health concern, ranking second in mortality and third in frequency among cancers worldwide. While only a small fraction of CRC cases can be attributed to inherited genetic mutations, the majority arise sporadically due to somatic mutations. Emerging evidence reveals gut microbiota dysbiosis to be a contributing factor, wherein polyketide synthase-positive Escherichia coli (pks+ E. coli) plays a pivotal role in CRC pathogenesis. pks+ bacteria produce colibactin, a genotoxic protein that causes deleterious effects on DNA within host colonocytes. In this review, we examine the role of the gut microbiota in colon carcinogenesis, elucidating how colibactin-producer bacteria induce DNA damage, promote genomic instability, disrupt the gut epithelial barrier, induce mucosal inflammation, modulate host immune responses, and influence cell cycle dynamics. Collectively, these actions foster a microenvironment conducive to tumor initiation and progression. Understanding the mechanisms underlying pks+ bacteria-mediated CRC development may pave the way for mass screening, early detection of tumors, and therapeutic strategies such as microbiota modulation, bacteria-targeted therapy, checkpoint inhibition of colibactin production and immunomodulatory pathways.
Collapse
Affiliation(s)
- Mohammad Sadeghi
- EA7375–EC2M3: Early, Detection of Colonic Cancer by Using Microbial & Molecular Markers, Paris East Créteil University (UPEC), 94010 Créteil, France;
| | - Denis Mestivier
- EA7375–EC2M3: Early, Detection of Colonic Cancer by Using Microbial & Molecular Markers, Paris East Créteil University (UPEC), 94010 Créteil, France;
| | - Iradj Sobhani
- EA7375–EC2M3: Early, Detection of Colonic Cancer by Using Microbial & Molecular Markers, Paris East Créteil University (UPEC), 94010 Créteil, France;
- Department of Gastroenterology, Assistance Publique–Hôpitaux de Paris (APHP), Henri Mondor Hospital, 94010 Créteil, France
| |
Collapse
|
|
12
|
Roszkowska P, Klimczak E, Ostrycharz E, Rączka A, Wojciechowska-Koszko I, Dybus A, Cheng YH, Yu YH, Mazgaj S, Hukowska-Szematowicz B. Small Intestinal Bacterial Overgrowth (SIBO) and Twelve Groups of Related Diseases-Current State of Knowledge. Biomedicines 2024; 12:1030. [PMID: 38790992 PMCID: PMC11117733 DOI: 10.3390/biomedicines12051030] [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: 03/24/2024] [Revised: 05/01/2024] [Accepted: 05/03/2024] [Indexed: 05/26/2024] Open
Abstract
The human gut microbiota creates a complex microbial ecosystem, characterized by its high population density, wide diversity, and complex interactions. Any imbalance of the intestinal microbiome, whether qualitative or quantitative, may have serious consequences for human health, including small intestinal bacterial overgrowth (SIBO). SIBO is defined as an increase in the number of bacteria (103-105 CFU/mL), an alteration in the bacterial composition, or both in the small intestine. The PubMed, Science Direct, Web of Science, EMBASE, and Medline databases were searched for studies on SIBO and related diseases. These diseases were divided into 12 groups: (1) gastrointestinal disorders; (2) autoimmune disease; (3) cardiovascular system disease; (4) metabolic disease; (5) endocrine disorders; (6) nephrological disorders; (7) dermatological diseases; (8) neurological diseases (9); developmental disorders; (10) mental disorders; (11) genetic diseases; and (12) gastrointestinal cancer. The purpose of this comprehensive review is to present the current state of knowledge on the relationships between SIBO and these 12 disease groups, taking into account risk factors and the causal context. This review fills the evidence gap on SIBO and presents a biological-medical approach to the problem, clearly showing the groups and diseases having a proven relationship with SIBO, as well as indicating groups within which research should continue to be expanded.
Collapse
Affiliation(s)
- Paulina Roszkowska
- Department of Diagnostic Immunology, Pomeranian Medical University, st. Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (P.R.); (I.W.-K.)
| | - Emilia Klimczak
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
| | - Ewa Ostrycharz
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
- Doctoral School, University of Szczecin, st. A. Mickiewicz 16, 71-412 Szczecin, Poland
- Molecular Biology and Biotechnology Center, University of Szczecin, st. Wąska 13, 71-412 Szczecin, Poland
| | - Aleksandra Rączka
- Department of Genetics, West Pomeranian University of Technology, st. Aleja Piastów 45, 70-311 Szczecin, Poland; (A.R.); (A.D.)
| | - Iwona Wojciechowska-Koszko
- Department of Diagnostic Immunology, Pomeranian Medical University, st. Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (P.R.); (I.W.-K.)
| | - Andrzej Dybus
- Department of Genetics, West Pomeranian University of Technology, st. Aleja Piastów 45, 70-311 Szczecin, Poland; (A.R.); (A.D.)
| | - Yeong-Hsiang Cheng
- Department of Biotechnology and Animal Science, National Ilan University, Yilan 26047, Taiwan; (Y.-H.C.); (Y.-H.Y.)
| | - Yu-Hsiang Yu
- Department of Biotechnology and Animal Science, National Ilan University, Yilan 26047, Taiwan; (Y.-H.C.); (Y.-H.Y.)
| | - Szymon Mazgaj
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
| | - Beata Hukowska-Szematowicz
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
- Molecular Biology and Biotechnology Center, University of Szczecin, st. Wąska 13, 71-412 Szczecin, Poland
| |
Collapse
|
|
13
|
Gościniak A, Rosiak N, Szymanowska D, Miklaszewski A, Cielecka-Piontek J. Prebiotic Systems Containing Anthocyanin-Rich Pomegranate Flower Extracts with Antioxidant and Antidiabetic Effects. Pharmaceutics 2024; 16:526. [PMID: 38675187 PMCID: PMC11054034 DOI: 10.3390/pharmaceutics16040526] [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: 03/04/2024] [Revised: 04/04/2024] [Accepted: 04/07/2024] [Indexed: 04/28/2024] Open
Abstract
Pomegranate flower extract, rich in anthocyanins, demonstrates beneficial health-promoting properties such as an anti-diabetic and antioxidant effect, among others. However, the potential health-promoting properties may be hindered by the low stability of anthocyanins. Therefore, the aim of our study was to assess whether stabilizing carriers, namely HP-γ-cyclodextrin (HP-γ-CD), α-cyclodextrin (α-CD), Methyl-β-cyclodextrin (Me-β-CD), Inulin (Inu) and Arabic gum (AGu) affect the antioxidant and antidiabetic activity of lyophilized pomegranate flower extract, how they influence stability, release profile, and whether the systems exhibit prebiotic activity. Interactions between pomegranate flower extract and these factors were analyzed using FT-IR. The structures were examined through microscopic imaging while for the prepared prebiotic systems, antidiabetic activity was determined and confirmed by the inhibition of α-amylase and α-glucosidase; antioxidant activity was expressed by DPPH and CUPRAC assays. The content of pelargonidin-3,5-glucoside in these systems was assessed using the HPLC method. The release profiles of pelargonidin-3,5-glucoside were examined in a medium at pH = 6.8 and pH = 1.2, and the stability was assessed after subjecting the systems to high temperatures (T = 90 °C). The prebiotic potential was evaluated for 10 prebiotic bacterial strains (Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus brevis Lactobacillus rhamnosus gg, Lactobacillus reuteri, Pediococcus pentosaceus, Lactococcus lactis, Lactobacillus fermentum lf, Streptococcus thermophilus). As a result of the conducted research, better functionalities of the obtained systems containing Pomegranate flower extract were proven in terms of prebiotic and antidiabetic effects. The obtained delivery systems for pelargonidin-3,5-glucoside allow for better use of its health-promoting effects.
Collapse
Affiliation(s)
- Anna Gościniak
- Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland; (A.G.); (N.R.); (D.S.)
| | - Natalia Rosiak
- Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland; (A.G.); (N.R.); (D.S.)
| | - Daria Szymanowska
- Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland; (A.G.); (N.R.); (D.S.)
- Department of Biotechnology and Food Microbiology, Poznan University of Life Sciences, Wojska Polskiego 48, 60-627 Poznan, Poland
| | - Andrzej Miklaszewski
- Institute of Materials Science and Engineering, Poznan University of Technology, Jana Pawła II 24, 61-138 Poznan, Poland;
| | - Judyta Cielecka-Piontek
- Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland; (A.G.); (N.R.); (D.S.)
| |
Collapse
|
|
14
|
Lan Z, Tang X, Lu M, Hu Z, Tang Z. The role of short-chain fatty acids in central nervous system diseases: A bibliometric and visualized analysis with future directions. Heliyon 2024; 10:e26377. [PMID: 38434086 PMCID: PMC10906301 DOI: 10.1016/j.heliyon.2024.e26377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 02/11/2024] [Accepted: 02/12/2024] [Indexed: 03/05/2024] Open
Abstract
Background Short-chain fatty acids (SCFAs) are thought to play a key role in the microbe-gut-brain axis and involve in the pathogenesis of a variety of neurological diseases. This study aimed to identify research hotspots and evolution trends in SCFAs in central nervous diseases (CNS) and examine current research trends. Methods The bibliometric analysis was performed using CiteSpace, and the results were visualized via network maps. Results From 2002 to 2022, 480 publications in the database met the criteria. On the country level, China produced the highest number of publications, while the United States had the highest centrality. On the institutional level, University College Cork contributed to the most publications, and John F. Cryan from this university was the key researcher with considerable academic influence. The article, the role of short-chain fatty acids in microbiota-gut-brain, written by Boushra Dalile et al., in 2019 was the most cited article. Furthermore, the journal Nutrients had the maximum number of publications, while Plos One was the most cited journal. "Gut microbiome", "SCFAs", and "central nervous system" were the three most frequent keywords. Among them, SCFAs had the highest centrality. "Animal model" was the keyword with the highest burst strength, with the latest burst keywords being "social behavior", "pathogenesis", and "insulin sensitive". In addition, the research topics on SCFAs in CNS diseases from 2002 to 2022 mainly focused on following aspects: SCFAs plays a key role in microbe-gut-brain crosstalk; The classification and definition of SCFAs in the field of CNS; Several CNS diseases that are closely related to SCFAs research; Mechanism and translational studies of SCFAs in the CNS diseases. And the hotspots over the past 5 years have gradually increased the attention to the therapeutic potential of SCFAs in the CNS diseases. Conclusion The research of SCFAs in CNS diseases is attracting growing attention. However, there is a lack of cooperation between countries and institutions, and additional measures are required to promote cooperation. The current evidence for an association between SCFAs and CNS diseases is preliminary and more work is needed to pinpoint the precise mechanism. Moreover, large-scale clinical trials are needed in the future to define the therapeutic potential of SCFAs in CNS diseases.
Collapse
Affiliation(s)
- Ziwei Lan
- Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
| | - Xiangqi Tang
- Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
| | - Ming Lu
- Hunan Provincial Key Laboratory of Neurorestoratology, The Second Affiliated Hospital, Hunan Normal University, Changsha, 410003, Hunan, China
| | - Zhiping Hu
- Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
| | - Zhenchu Tang
- Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
| |
Collapse
|
|
15
|
Colonetti T, Limas Carmo Teixeira D, Grande AJ, Rodrigues Uggioni ML, Generoso J, Harding S, Rodriguez-Mateos A, Rech P, Rosa Silva F, Toreti I, Ceretta L, Rosa MI. The role of intestinal microbiota on pre-eclampsia: Systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2023; 291:49-58. [PMID: 37826991 DOI: 10.1016/j.ejogrb.2023.10.003] [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: 04/06/2023] [Accepted: 10/01/2023] [Indexed: 10/14/2023]
Abstract
AIM To investigate differences between gut microbiota diversity and composition of healthy pregnant women and women with pre-eclampsia (PE). METHODS AND RESULTS This is a systematic review and meta-analysis of the literature, in which the terms "pre-eclampsia", "gastrointestinal microbiome" and "pregnant women" were used to search MEDLINE (PubMed), BVS (LILACS and others), Embase (Elsevier) and Cochrane Library, including observational studies and case-control that investigated changes in the gut microbiota during pregnancy. Six studies were included, with 479 pregnant women. A significantly lower gut microbiota alpha diversity measured as the Shannon index was found in pregnant women with PE in comparison with healthy controls (SMD: -0.47; 95 %IC: -0.77 to -0.18; P = 0.02; I2 = 0 %; three studies, 179 participants), while no significant differences were found in the relative abundance of Bacteroidetes, Firmicutes, Actinobacteria, and Proteobacteria, despite significant differences reported in the individual studies. CONCLUSION Pregnant women with PE have lower gut microbiome diversity, however, there is insufficient evidence to determine whether there are changes in gut microbiota composition. SIGNIFICANCE AND IMPACT OF THE STUDY The gut microbiota can be a new treatment target to try to prevent changes in maternal bacterial proportions, aiming to reduce complications during pregnancy.
Collapse
Affiliation(s)
- Tamy Colonetti
- Translational Biomedicine Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
| | - Diandra Limas Carmo Teixeira
- Translational Biomedicine Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - Antonio José Grande
- Laboratory of Evidence-based Health, Universidade Estadual de Mato Grosso do Sul, Campo Grande, MS, Brazil
| | - Maria Laura Rodrigues Uggioni
- Translational Biomedicine Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - Jaqueline Generoso
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
| | - Seeromanie Harding
- Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, SE1 9NH London, UK
| | - Ana Rodriguez-Mateos
- Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, SE1 9NH London, UK
| | - Peterson Rech
- Translational Biomedicine Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - Fabio Rosa Silva
- Translational Biomedicine Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - Indianara Toreti
- Translational Biomedicine Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - Luciane Ceretta
- Translational Biomedicine Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - Maria Inês Rosa
- Translational Biomedicine Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| |
Collapse
|
|
16
|
Złotek M, Kurowska A, Herbet M, Piątkowska-Chmiel I. GLP-1 Analogs, SGLT-2, and DPP-4 Inhibitors: A Triad of Hope for Alzheimer's Disease Therapy. Biomedicines 2023; 11:3035. [PMID: 38002034 PMCID: PMC10669527 DOI: 10.3390/biomedicines11113035] [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: 10/22/2023] [Revised: 11/07/2023] [Accepted: 11/10/2023] [Indexed: 11/26/2023] Open
Abstract
Alzheimer's is a prevalent, progressive neurodegenerative disease marked by cognitive decline and memory loss. The disease's development involves various pathomechanisms, including amyloid-beta accumulation, neurofibrillary tangles, oxidative stress, inflammation, and mitochondrial dysfunction. Recent research suggests that antidiabetic drugs may enhance neuronal survival and cognitive function in diabetes. Given the well-documented correlation between diabetes and Alzheimer's disease and the potential shared mechanisms, this review aimed to comprehensively assess the potential of new-generation anti-diabetic drugs, such as GLP-1 analogs, SGLT-2 inhibitors, and DPP-4 inhibitors, as promising therapeutic approaches for Alzheimer's disease. This review aims to comprehensively assess the potential therapeutic applications of novel-generation antidiabetic drugs, including GLP-1 analogs, SGLT-2 inhibitors, and DPP-4 inhibitors, in the context of Alzheimer's disease. In our considered opinion, antidiabetic drugs offer a promising avenue for groundbreaking developments and have the potential to revolutionize the landscape of Alzheimer's disease treatment.
Collapse
Affiliation(s)
| | | | | | - Iwona Piątkowska-Chmiel
- Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 8b Street, 20-090 Lublin, Poland; (M.Z.); (A.K.); (M.H.)
| |
Collapse
|
|
17
|
Zikou E, Dovrolis N, Dimosthenopoulos C, Gazouli M, Makrilakis K. The Effect of Probiotic Supplements on Metabolic Parameters of People with Type 2 Diabetes in Greece-A Randomized, Double-Blind, Placebo-Controlled Study. Nutrients 2023; 15:4663. [PMID: 37960315 PMCID: PMC10647535 DOI: 10.3390/nu15214663] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 10/16/2023] [Accepted: 10/31/2023] [Indexed: 11/15/2023] Open
Abstract
The role of probiotic supplementation in type 2 diabetes (T2D) treatment is controversial. The present study aimed to assess the effects of a multi-strain probiotic supplement (LactoLevureR (containing Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii)) over 6 months, primarily on glycemic control as well as on lipid levels and alterations in the gut microbiome, among individuals with T2D residing in Greece. A total of 91 adults with T2D (mean age [±SD] 65.12 ± 10.92 years, 62.6% males) were randomized to receive the probiotic supplement or a matching placebo capsule, once daily, for 6 months. Blood chemistries and anthropometric parameters were conducted every 3 months, and stool samples were collected at baseline and at 6 months. Significant reductions in HbA1c, fasting blood glucose, and total cholesterol were observed in participants treated with the probiotic supplement (n = 46) compared to the controls (n = 45), even after adjustment for a greater decrease in adiposity (waist circumference). Although there were no statistically significant differences in the diversity of the gut microbiome (α and β diversity), the administration of probiotics did influence several genera, metabolites, and key enzymes associated with diabetes. Overall, the administration of the multi-strain probiotic LactoLevureR over a 6-month period in individuals with T2D was well-tolerated and had a positive impact on metabolic parameters, alongside improvements in indices of adiposity.
Collapse
Affiliation(s)
- Eva Zikou
- First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Laiko General Hospital, 11527 Athens, Greece; (E.Z.); (C.D.)
| | - Nikolas Dovrolis
- Department of Basic Medical Sciences, Laboratory of Biology, National and Kapodistrian University of Athens Medical School, 11527 Athens, Greece; (N.D.); (M.G.)
| | - Charilaos Dimosthenopoulos
- First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Laiko General Hospital, 11527 Athens, Greece; (E.Z.); (C.D.)
| | - Maria Gazouli
- Department of Basic Medical Sciences, Laboratory of Biology, National and Kapodistrian University of Athens Medical School, 11527 Athens, Greece; (N.D.); (M.G.)
| | - Konstantinos Makrilakis
- First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Laiko General Hospital, 11527 Athens, Greece; (E.Z.); (C.D.)
| |
Collapse
|
|
18
|
Halma MTJ, Tuszynski JA, Marik PE. Cancer Metabolism as a Therapeutic Target and Review of Interventions. Nutrients 2023; 15:4245. [PMID: 37836529 PMCID: PMC10574675 DOI: 10.3390/nu15194245] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 09/20/2023] [Accepted: 09/26/2023] [Indexed: 10/15/2023] Open
Abstract
Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be affected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have an altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to target cancers metabolically by depriving them of glucose. In addition to dietary and lifestyle modifications which work on tumors metabolically, there are a panoply of nutritional supplements and repurposed drugs associated with cancer prevention and better treatment outcomes. These interventions and their evidentiary basis are covered in the latter half of this review to guide future cancer treatment.
Collapse
Affiliation(s)
- Matthew T. J. Halma
- Department of Physics and Astronomy, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
- EbMC Squared CIC, Bath BA2 4BL, UK
| | - Jack A. Tuszynski
- Department of Physics, University of Alberta, 11335 Saskatchewan Dr NW, Edmonton, AB T6G 2M9, Canada
- Department of Data Science and Engineering, The Silesian University of Technology, 44-100 Gliwice, Poland
- DIMEAS, Politecnico di Torino, Corso Duca degli Abruzzi 24, I-1029 Turin, Italy
| | - Paul E. Marik
- Frontline COVID-19 Critical Care Alliance, Washington, DC 20036, USA
| |
Collapse
|
|
19
|
Handsley-Davis M, Anderson MZ, Bader AC, Ehau-Taumaunu H, Fox K, Kowal E, Weyrich LS. Microbiome ownership for Indigenous peoples. Nat Microbiol 2023; 8:1777-1786. [PMID: 37770744 DOI: 10.1038/s41564-023-01470-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 08/11/2023] [Indexed: 09/30/2023]
Abstract
Several studies have reported increased microbial diversity, or distinct microbial community compositions, in the microbiomes of Indigenous peoples around the world. However, there is a widespread failure to include Indigenous cultures and perspectives in microbiome research programmes, and ethical issues pertaining to microbiome research involving Indigenous participants have not received enough attention. We discuss the benefits and risks arising from microbiome research involving Indigenous peoples and analyse microbiome ownership as an ethical concept in this context. We argue that microbiome ownership represents an opportunity for Indigenous peoples to steward and protect their resident microbial communities at every stage of research.
Collapse
Affiliation(s)
- Matilda Handsley-Davis
- School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia
- ARC Centre of Excellence for Australian Biodiversity and Heritage, University of Wollongong, Wollongong, New South Wales, Australia
| | - Matthew Z Anderson
- Department of Microbiology, The Ohio State University, Columbus, OH, USA
- Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA
- Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, WI, USA
- Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, USA
| | - Alyssa C Bader
- Department of Anthropology, McGill University, Montreal, Quebec, Canada
| | - Hanareia Ehau-Taumaunu
- Department of Plant Pathology and Environmental Microbiology, The Pennsylvania State University, State College, PA, USA
| | - Keolu Fox
- Department of Anthropology, Global Health Program, and Indigenous Futures Institute, University of California, San Diego, CA, USA
| | - Emma Kowal
- ARC Centre of Excellence for Australian Biodiversity and Heritage, University of Wollongong, Wollongong, New South Wales, Australia
- Alfred Deakin Institute for Citizenship and Globalisation, Deakin University, Melbourne, Victoria, Australia
| | - Laura S Weyrich
- School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
- ARC Centre of Excellence for Australian Biodiversity and Heritage, University of Wollongong, Wollongong, New South Wales, Australia.
- Department of Anthropology and Huck Institutes of Life Sciences, The Pennsylvania State University, State College, PA, USA.
| |
Collapse
|
|
20
|
Patra D, Banerjee D, Ramprasad P, Roy S, Pal D, Dasgupta S. Recent insights of obesity-induced gut and adipose tissue dysbiosis in type 2 diabetes. Front Mol Biosci 2023; 10:1224982. [PMID: 37842639 PMCID: PMC10575740 DOI: 10.3389/fmolb.2023.1224982] [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: 05/18/2023] [Accepted: 09/14/2023] [Indexed: 10/17/2023] Open
Abstract
An imbalance in microbial homeostasis, referred to as dysbiosis, is critically associated with the progression of obesity-induced metabolic disorders including type 2 diabetes (T2D). Alteration in gut microbial diversity and the abundance of pathogenic bacteria disrupt metabolic homeostasis and potentiate chronic inflammation, due to intestinal leakage or release of a diverse range of microbial metabolites. The obesity-associated shifts in gut microbial diversity worsen the triglyceride and cholesterol level that regulates adipogenesis, lipolysis, and fatty acid oxidation. Moreover, an intricate interaction of the gut-brain axis coupled with the altered microbiome profile and microbiome-derived metabolites disrupt bidirectional communication for instigating insulin resistance. Furthermore, a distinct microbial community within visceral adipose tissue is associated with its dysfunction in obese T2D individuals. The specific bacterial signature was found in the mesenteric adipose tissue of T2D patients. Recently, it has been shown that in Crohn's disease, the gut-derived bacterium Clostridium innocuum translocated to the mesenteric adipose tissue and modulates its function by inducing M2 macrophage polarization, increasing adipogenesis, and promoting microbial surveillance. Considering these facts, modulation of microbiota in the gut and adipose tissue could serve as one of the contemporary approaches to manage T2D by using prebiotics, probiotics, or faecal microbial transplantation. Altogether, this review consolidates the current knowledge on gut and adipose tissue dysbiosis and its role in the development and progression of obesity-induced T2D. It emphasizes the significance of the gut microbiota and its metabolites as well as the alteration of adipose tissue microbiome profile for promoting adipose tissue dysfunction, and identifying novel therapeutic strategies, providing valuable insights and directions for future research and potential clinical interventions.
Collapse
Affiliation(s)
- Debarun Patra
- Department of Biomedical Engineering, Indian Institute of Technology Ropar, Punjab, Punjab, India
| | - Dipanjan Banerjee
- Department of Molecular Biology and Biotechnology, Tezpur University, Napaam, Assam, India
| | - Palla Ramprasad
- Department of Biomedical Engineering, Indian Institute of Technology Ropar, Punjab, Punjab, India
| | - Soumyajit Roy
- Department of Biomedical Engineering, Indian Institute of Technology Ropar, Punjab, Punjab, India
| | - Durba Pal
- Department of Biomedical Engineering, Indian Institute of Technology Ropar, Punjab, Punjab, India
| | - Suman Dasgupta
- Department of Molecular Biology and Biotechnology, Tezpur University, Napaam, Assam, India
| |
Collapse
|
|
21
|
Ma Z, Sun W, Wang L, Wang Y, Pan B, Su X, Li H, Zhang H, Lv S, Wang H. Integrated 16S rRNA sequencing and nontargeted metabolomics analysis to reveal the mechanisms of Yu-Ye Tang on type 2 diabetes mellitus rats. Front Endocrinol (Lausanne) 2023; 14:1159707. [PMID: 37732114 PMCID: PMC10507721 DOI: 10.3389/fendo.2023.1159707] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 08/21/2023] [Indexed: 09/22/2023] Open
Abstract
INTRODUCTION Yu-Ye Tang (YYT) is a classical formula widely used in treatment of type 2 diabetes mellitus (T2DM). However, the specific mechanism of YYT in treating T2DM is not clear. METHODS The aim of this study was to investigate the therapeutic effect of YYT on T2DM by establishing a rat model of T2DM. The mechanism of action of YYT was also explored through investigating gut microbiota and serum metabolites. RESULTS The results indicated YYT had significant therapeutic effects on T2DM. Moreover, YYT could increase the abundance of Lactobacillus, Candidatus_Saccharimonas, UCG-005, Bacteroides and Blautia while decrease the abundance of and Allobaculum and Desulfovibrio in gut microbiota of T2DM rats. Nontargeted metabolomics analysis showed YYT treatment could regulate arachidonic acid metabolism, alanine, aspartate and glutamate metabolism, arginine and proline metabolism, glycerophospholipid metabolism, pentose and glucuronate interconversions, phenylalanine metabolism, steroid hormone biosynthesis, terpenoid backbone biosynthesis, tryptophan metabolism, and tyrosine metabolism in T2DM rats. DISCUSSION In conclusion, our research showed that YYT has a wide range of therapeutic effects on T2DM rats, including antioxidative and anti-inflammatory effects. Furthermore, YYT corrected the altered gut microbiota and serum metabolites in T2DM rats. This study suggests that YYT may have a therapeutic impact on T2DM by regulating gut microbiota and modulating tryptophan and glycerophospholipid metabolism, which are potential key pathways in treating T2DM.
Collapse
Affiliation(s)
- Ziang Ma
- Graduate School of Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Wenjuan Sun
- Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Lixin Wang
- Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Yuansong Wang
- Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Baochao Pan
- Graduate School of Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Xiuhai Su
- Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Hanzhou Li
- College of Integrated Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Hui Zhang
- Graduate School of Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Shuquan Lv
- Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Hongwu Wang
- College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| |
Collapse
|
|
22
|
Filippone A, Rossi C, Rossi MM, Di Micco A, Maggiore C, Forcina L, Natale M, Costantini L, Merendino N, Di Leone A, Franceschini G, Masetti R, Magno S. Endocrine Disruptors in Food, Estrobolome and Breast Cancer. J Clin Med 2023; 12:jcm12093158. [PMID: 37176599 PMCID: PMC10178963 DOI: 10.3390/jcm12093158] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/17/2023] [Accepted: 04/26/2023] [Indexed: 05/15/2023] Open
Abstract
The microbiota is now recognized as one of the major players in human health and diseases, including cancer. Regarding breast cancer (BC), a clear link between microbiota and oncogenesis still needs to be confirmed. Yet, part of the bacterial gene mass inside the gut, constituting the so called "estrobolome", influences sexual hormonal balance and, since the increased exposure to estrogens is associated with an increased risk, may impact on the onset, progression, and treatment of hormonal dependent cancers (which account for more than 70% of all BCs). The hormonal dependent BCs are also affected by environmental and dietary endocrine disruptors and phytoestrogens which interact with microbiota in a bidirectional way: on the one side disruptors can alter the composition and functions of the estrobolome, ad on the other the gut microbiota influences the metabolism of endocrine active food components. This review highlights the current evidence about the complex interplay between endocrine disruptors, phytoestrogens, microbiome, and BC, within the frames of a new "oncobiotic" perspective.
Collapse
Affiliation(s)
- Alessio Filippone
- Center for Integrative Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Cristina Rossi
- Center for Integrative Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Maria Maddalena Rossi
- Center for Integrative Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Annalisa Di Micco
- Center for Integrative Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Claudia Maggiore
- Center for Integrative Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Luana Forcina
- Center for Integrative Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Maria Natale
- Breast Cancer Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Lara Costantini
- Department of Ecological and Biological Sciences (DEB), Tuscia University, Largo dell'Università snc, 01100 Viterbo, Italy
| | - Nicolò Merendino
- Department of Ecological and Biological Sciences (DEB), Tuscia University, Largo dell'Università snc, 01100 Viterbo, Italy
| | - Alba Di Leone
- Breast Cancer Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Gianluca Franceschini
- Breast Cancer Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Women's Health Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Riccardo Masetti
- Breast Cancer Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Women's Health Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Stefano Magno
- Center for Integrative Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| |
Collapse
|
|
23
|
Aldirawi H, Morales FG. Univariate and Multivariate Statistical Analysis of Microbiome Data: An Overview. Appl Microbiol 2023. [DOI: 10.3390/applmicrobiol3020023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/30/2023]
Abstract
Microbiome data is high dimensional, sparse, compositional, and over-dispersed. Therefore, modeling microbiome data is very challenging and it is an active research area. Microbiome analysis has become a progressing area of research as microorganisms constitute a large part of life. Since many methods of microbiome data analysis have been presented, this review summarizes the challenges, methods used, and the advantages and disadvantages of those methods, to serve as an updated guide for those in the field. This review also compared different methods of analysis to progress the development of newer methods.
Collapse
|
|
24
|
Usyk M, Peters BA, Karthikeyan S, McDonald D, Sollecito CC, Vazquez-Baeza Y, Shaffer JP, Gellman MD, Talavera GA, Daviglus ML, Thyagarajan B, Knight R, Qi Q, Kaplan R, Burk RD. Comprehensive evaluation of shotgun metagenomics, amplicon sequencing, and harmonization of these platforms for epidemiological studies. CELL REPORTS METHODS 2023; 3:100391. [PMID: 36814836 PMCID: PMC9939430 DOI: 10.1016/j.crmeth.2022.100391] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 11/28/2022] [Accepted: 12/20/2022] [Indexed: 01/24/2023]
Abstract
In a large cohort of 1,772 participants from the Hispanic Community Health Study/Study of Latinos with overlapping 16SV4 rRNA gene (bacterial amplicon), ITS1 (fungal amplicon), and shotgun sequencing data, we demonstrate that 16SV4 amplicon sequencing and shotgun metagenomics offer the same level of taxonomic accuracy for bacteria at the genus level even at shallow sequencing depths. In contrast, for fungal taxa, we did not observe meaningful agreements between shotgun and ITS1 amplicon results. Finally, we show that amplicon and shotgun data can be harmonized and pooled to yield larger microbiome datasets with excellent agreement (<1% effect size variance across three independent outcomes) using pooled amplicon/shotgun data compared to pure shotgun metagenomic analysis. Thus, there are multiple approaches to study the microbiome in epidemiological studies, and we provide a demonstration of a powerful pooling approach that will allow researchers to leverage the massive amount of amplicon sequencing data generated over the last two decades.
Collapse
Affiliation(s)
- Mykhaylo Usyk
- Department of Pediatrics (Genetic Medicine), Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
- Department of Epidemiology and Population Health, NYU School of Medicine, New York, NY, USA
| | - Brandilyn A. Peters
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Smruthi Karthikeyan
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Daniel McDonald
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Christopher C. Sollecito
- Department of Pediatrics (Genetic Medicine), Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
| | - Yoshiki Vazquez-Baeza
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
| | - Justin P. Shaffer
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Marc D. Gellman
- Department of Psychology, University of Miami, Miami, FL, USA
| | - Gregory A. Talavera
- Division of Health Promotion and Behavioral Science, San Diego State University, San Diego, CA, USA
| | - Martha L. Daviglus
- Department of Medicine, University of Illinois-Chicago, Chicago, IL, USA
| | - Bharat Thyagarajan
- Department of Laboratory Medicine and Pathology, University of Minnesota Medical Center, Minneapolis, MN, USA
| | - Rob Knight
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
- Departments of Computer Science and Engineering, and Bioengineering, University of California San Diego, La Jolla, CA, USA
| | - Qibin Qi
- Department of Epidemiology and Population Health, NYU School of Medicine, New York, NY, USA
| | - Robert Kaplan
- Department of Epidemiology and Population Health, NYU School of Medicine, New York, NY, USA
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Robert D. Burk
- Department of Pediatrics (Genetic Medicine), Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
- Departments of Microbiology & Immunology, and Obstetrics, Gynecology & Women’s Health, Albert Einstein College of Medicine, Bronx, NY, USA
| |
Collapse
|
|
25
|
Song H, Ling W, Zhao N, Plantinga AM, Broedlow CA, Klatt NR, Hensley-McBain T, Wu MC. Accommodating multiple potential normalizations in microbiome associations studies. BMC Bioinformatics 2023; 24:22. [PMID: 36658484 PMCID: PMC9850542 DOI: 10.1186/s12859-023-05147-w] [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: 07/06/2022] [Accepted: 01/12/2023] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Microbial communities are known to be closely related to many diseases, such as obesity and HIV, and it is of interest to identify differentially abundant microbial species between two or more environments. Since the abundances or counts of microbial species usually have different scales and suffer from zero-inflation or over-dispersion, normalization is a critical step before conducting differential abundance analysis. Several normalization approaches have been proposed, but it is difficult to optimize the characterization of the true relationship between taxa and interesting outcomes. RESULTS: To avoid the challenge of picking an optimal normalization and accommodate the advantages of several normalization strategies, we propose an omnibus approach. Our approach is based on a Cauchy combination test, which is flexible and powerful by aggregating individual p values. We also consider a truncated test statistic to prevent substantial power loss. We experiment with a basic linear regression model as well as recently proposed powerful association tests for microbiome data and compare the performance of the omnibus approach with individual normalization approaches. Experimental results show that, regardless of simulation settings, the new approach exhibits power that is close to the best normalization strategy, while controling the type I error well. CONCLUSIONS: The proposed omnibus test releases researchers from choosing among various normalization methods and it is an aggregated method that provides the powerful result to the underlying optimal normalization, which requires tedious trial and error. While the power may not exceed the best normalization, it is always much better than using a poor choice of normalization.
Collapse
Affiliation(s)
- Hoseung Song
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA USA
| | - Wodan Ling
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA USA
| | - Ni Zhao
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD USA
| | - Anna M. Plantinga
- Department of Mathematics and Statistics, Williams College, Williamstown, MA USA
| | - Courtney A. Broedlow
- Division of Surgical Outcomes and Precision Medicine Research, Department of Surgery, University of Minnesota School of Medicine, Minneapolis, MN USA
| | - Nichole R. Klatt
- Division of Surgical Outcomes and Precision Medicine Research, Department of Surgery, University of Minnesota School of Medicine, Minneapolis, MN USA
| | | | - Michael C. Wu
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA USA
| |
Collapse
|
|
26
|
Zhang H, Li H, Pan B, Zhang S, Su X, Sun W, Zhang T, Zhang Z, Lv S, Cui H. Integrated 16S rRNA Sequencing and Untargeted Metabolomics Analysis to Reveal the Protective Mechanisms of Polygonatum sibiricum Polysaccharide on Type 2 Diabetes Mellitus Model Rats. Curr Drug Metab 2023; 24:270-282. [PMID: 37038712 DOI: 10.2174/1389200224666230406114012] [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: 09/26/2022] [Revised: 02/07/2023] [Accepted: 02/10/2023] [Indexed: 04/12/2023]
Abstract
BACKGROUND Polygonatum sibiricum polysaccharide (PSP) can improve insulin resistance and inhibit oxidative stress. However, the detailed anti-diabetic mechanism of PSP is still poorly defined. METHODS In this study, the anti-diabetic, anti-inflammatory and anti-oxidative effects of PSP were evaluated on a type 2 diabetes mellitus (T2DM) rat model. Furthermore, we investigated the changes in gut microbiota and serum metabolites in T2DM rats after PSP treatment through 16S rRNA sequencing and untargeted metabolomics analyses. RESULTS Our results showed that PSP exhibited significant anti-diabetic, anti-inflammatory and anti-oxidative effects on T2DM model rats. In addition, 16S rRNA sequencing showed that PSP treatment decreased the Firmicutes/ Bacteroidetes ratio in the gut. At the genus level, PSP treatment increased the relative abundances of Blautia, Adlercreutzia, Akkermansia and Parabacteroides while decreasing Prevotella, Megamonas funiformis and Escherichia. Untargeted metabolomics analysis revealed that PSP treatment could affect 20 metabolites, including hexanoylglycine, (±)5(6)-DiHET, ecgonine, L-cysteine-S-sulfate, epitestosterone, (±)12(13)-DiHOME, glutathione, L-ornithine, Dmannose 6-phosphate, L-fucose, L-tryptophan, L-kynurenine, serotonin, melatonin, 3-hydroxyanthranilic acid, xylitol, UDP-D-glucuronate, hydroxyproline, 4-guanidinobutyric acid, D-proline in T2DM model rats, these metabolites are associated with arginine and proline metabolism, tryptophan metabolism, amino sugar and nucleotide sugar metabolism, pentose and glucuronate interconversions, glutathione metabolism, arginine biosynthesis, ascorbate and aldarate metabolism pathways. Spearman correlation analysis results showed that the modulatory effects of PSP on the arginine and proline metabolism, tryptophan metabolism, and glutathione metabolism pathways were related to the regulation of Prevotella, Megamonas funiformis, Escherichia, Blautia and Adlercreutzia. CONCLUSION Our research revealed the therapeutic, anti-inflammatory and anti-oxidative effects of PSP on T2DM. The mechanisms of PSP on T2DM are associated with improving the dysbiosis of gut microbiota and regulating arginine and proline metabolism, tryptophan metabolism, and glutathione metabolism in serum.
Collapse
Affiliation(s)
- Hui Zhang
- Department of Endocrinology and Metabolism, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Hanzhou Li
- Department of Endocrinology and Metabolism, Chengde Medical University, Chengde, China
| | - Baochao Pan
- Department of Endocrinology and Metabolism, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Shufang Zhang
- Department of Endocrinology and Metabolism, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Xiuhai Su
- Department of Endocrinology and Metabolism, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Wenjuan Sun
- Department of Endocrinology and Metabolism, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Tianyu Zhang
- Department of Endocrinology and Metabolism, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Zhaiyi Zhang
- Department of Endocrinology and Metabolism, Tianjing University of Traditional Chinese Medicine, Tianjin, China
| | - Shuquan Lv
- Department of Endocrinology and Metabolism, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Huantian Cui
- Faculty of Life Sciences, Shandong University, Shandong, China
| |
Collapse
|
|
27
|
Sroka N, Rydzewska-Rosołowska A, Kakareko K, Rosołowski M, Głowińska I, Hryszko T. Show Me What You Have Inside-The Complex Interplay between SIBO and Multiple Medical Conditions-A Systematic Review. Nutrients 2022; 15:nu15010090. [PMID: 36615748 PMCID: PMC9824151 DOI: 10.3390/nu15010090] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 12/18/2022] [Accepted: 12/20/2022] [Indexed: 12/28/2022] Open
Abstract
The microbiota, as a complex of microorganisms in a particular ecosystem, is part of the wider term-microbiome, which is defined as the set of all genetic content in the microbial community. Imbalanced gut microbiota has a great impact on the homeostasis of the organism. Dysbiosis, as a disturbance in bacterial balance, might trigger or exacerbate the course of different pathologies. Small intestinal bacterial overgrowth (SIBO) is a disorder characterized by differences in quantity, quality, and location of the small intestine microbiota. SIBO underlies symptoms associated with functional gastrointestinal disorders (FGD) as well as may alter the presentation of chronic diseases such as heart failure, diabetes, etc. In recent years there has been growing interest in the influence of SIBO and its impact on the whole human body as well as individual systems. Therefore, we aimed to investigate the co-existence of SIBO with different medical conditions. The PubMed database was searched up to July 2022 and we found 580 original studies; inclusion and exclusion criteria let us identify 112 eligible articles, which are quoted in this paper. The present SIBO diagnostic methods could be divided into two groups-invasive, the gold standard-small intestine aspirate culture, and non-invasive, breath tests (BT). Over the years scientists have explored SIBO and its associations with other diseases. Its role has been confirmed not only in gastroenterology but also in cardiology, endocrinology, neurology, rheumatology, and nephrology. Antibiotic therapy could reduce SIBO occurrence resulting not only in the relief of FGD symptoms but also manifestations of comorbid diseases. Although more research is needed, the link between SIBO and other diseases is an important pathway for scientists to follow.
Collapse
Affiliation(s)
- Natalia Sroka
- 2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Białystok, 15-276 Białystok, Poland
- Correspondence:
| | - Alicja Rydzewska-Rosołowska
- 2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Białystok, 15-276 Białystok, Poland
| | - Katarzyna Kakareko
- 2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Białystok, 15-276 Białystok, Poland
| | - Mariusz Rosołowski
- Department of Internal Medicine and Hypertension, Medical University of Białystok, 15-540 Białystok, Poland
| | - Irena Głowińska
- 2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Białystok, 15-276 Białystok, Poland
| | - Tomasz Hryszko
- 2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Białystok, 15-276 Białystok, Poland
| |
Collapse
|
|
28
|
Ye J, Wu Z, Zhao Y, Zhang S, Liu W, Su Y. Role of gut microbiota in the pathogenesis and treatment of diabetes mullites: Advanced research-based review. Front Microbiol 2022; 13:1029890. [PMID: 36338058 PMCID: PMC9627042 DOI: 10.3389/fmicb.2022.1029890] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 09/26/2022] [Indexed: 02/05/2023] Open
Abstract
Gut microbiota plays an important role in the proper functioning of human organisms, while its dysbiosis is associated with disease in various body organs. Diabetes mellitus (DM) is a set of heterogeneous metabolic diseases characterized by hyperglycemia caused by direct or indirect insulin deficiency. There is growing evidence that gut microbiota dysbiosis is closely linked to the development of DM. Gut microbiota composition changes in type 1 diabetes mullites (T1DM) and type 2 diabetes mullites (T2DM) patients, which may cause gut leakiness and uncontrolled entry of antigens into the circulation system, triggering an immune response that damages the isle β cells or metabolic disorders. This review summarizes gut microbiota composition in healthy individuals and compares it to diabetes mullites patients. The possible pathogenesis by which gut microbiota dysbiosis causes DM, particularly gut leakiness and changes in gut microbiota metabolites is also discussed. It also presents the process of microbial-based therapies of DM.
Collapse
Affiliation(s)
- Junjun Ye
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Shantou University Medical College, Shantou, China
| | - Zezhen Wu
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Yifei Zhao
- School of Nursing, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Shuo Zhang
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Weiting Liu
- School of Nursing, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Yu Su
- Center of Teaching Evaluation and Faculty Development, Anhui University of Chinese Medicine, Hefei, China
| |
Collapse
|
|
29
|
Merenstein C, Bushman FD, Collman RG. Alterations in the respiratory tract microbiome in COVID-19: current observations and potential significance. MICROBIOME 2022; 10:165. [PMID: 36195943 PMCID: PMC9532226 DOI: 10.1186/s40168-022-01342-8] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 08/02/2022] [Indexed: 06/16/2023]
Abstract
SARS-CoV-2 infection causes COVID-19 disease, which can result in consequences ranging from undetectable to fatal, focusing attention on the modulators of outcomes. The respiratory tract microbiome is thought to modulate the outcomes of infections such as influenza as well as acute lung injury, raising the question to what degree does the airway microbiome influence COVID-19? Here, we review the results of 56 studies examining COVID-19 and the respiratory tract microbiome, summarize the main generalizations, and point to useful avenues for further research. Although the results vary among studies, a few consistent findings stand out. The diversity of bacterial communities in the oropharynx typically declined with increasing disease severity. The relative abundance of Haemophilus and Neisseria also declined with severity. Multiple microbiome measures tracked with measures of systemic immune responses and COVID outcomes. For many of the conclusions drawn in these studies, the direction of causality is unknown-did an alteration in the microbiome result in increased COVID severity, did COVID severity alter the microbiome, or was some third factor the primary driver, such as medication use. Follow-up mechanistic studies can help answer these questions. Video Abstract.
Collapse
Affiliation(s)
- Carter Merenstein
- Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA
| | - Frederic D. Bushman
- Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA
| | - Ronald G. Collman
- Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 USA
| |
Collapse
|
|
30
|
Yi ZY, Chen L, Wang Y, He D, Zhao D, Zhang SH, Yu R, Huang JH. The potential mechanism of Liu-Wei-Di-Huang Pills in treatment of type 2 diabetic mellitus: from gut microbiota to short-chain fatty acids metabolism. Acta Diabetol 2022; 59:1295-1308. [PMID: 35857109 DOI: 10.1007/s00592-022-01922-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 06/11/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) has already become a global pandemic. Recently, reports showed its pathogenesis was closely related to a disorder of gut microbiota. In China, the Liu-Wei-Di-Huang Pills (LWDH) have treated T2DM for thousands of years. However, its therapeutic mechanism associated with gut microbiota is worthy of further study. AIMS This study aims to investigate the effects of LWDH on T2DM by regulating gut microbiota and short-chain fatty acids (SCFAs) in Goto-Kakizaki (GK) rats. METHODS T2DM models were successfully established based on GK rats and administrated with LWDH. The changes in fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and serum insulin (INS) were determined, and the immunohistochemical (IHC) method was used to test INS expression in pancreas. The 16S-ribosomal DNA (16S rDNA) sequencing analysis assessed gut microbiota structural changes; a gas chromatography-mass spectrometer (GC-MS)-based metabolomics method was adopted to detect SCFA levels. The pathological morphology of jejunum was detected by hematoxylin-eosin (H&E) staining, and the expression of GPR43, GPR41, GLP-1, and GLP-1R was evaluated by qRT-PCR and ELISA, respectively. RESULTS We observed that GK rats treated with LWDH: (a) has altered the microbial structure and promoted the abundance of bacteria in Firmicutes, including Lactobacillus, Allobaculum, and Ruminococcus_2, (b) increased SCFAs levels involving acetic acid, propionic acid, and butyric acid and (c) alleviated T2DM and jejunum injuries potentially based on SCFAs-GPR43/41-GLP-1 pathway. CONCLUSION LWDH could improve T2DM by regulating gut microbiota and SCFAs, and the therapeutic mechanism might be related to the SCFAs-GPR43/41-GLP-1 pathway.
Collapse
Affiliation(s)
- Zi-Yang Yi
- Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410013, Hunan, People's Republic of China
| | - Lin Chen
- Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410013, Hunan, People's Republic of China
| | - Yan Wang
- H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
| | - Dan He
- Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410013, Hunan, People's Republic of China
| | - Di Zhao
- Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410013, Hunan, People's Republic of China
| | - Shui-Han Zhang
- Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410013, Hunan, People's Republic of China
| | - Rong Yu
- Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410013, Hunan, People's Republic of China.
- Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, People's Republic of China.
| | - Jian-Hua Huang
- Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410013, Hunan, People's Republic of China.
- Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, People's Republic of China.
| |
Collapse
|
|
31
|
Guo J, Liu H, Zhao D, Pan C, Jin X, Hu Y, Gao X, Rao P, Liu S. Glucose-lowering effects of orally administered superoxide dismutase in type 2 diabetic model rats. NPJ Sci Food 2022; 6:36. [PMID: 35987753 PMCID: PMC9392803 DOI: 10.1038/s41538-022-00151-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 07/26/2022] [Indexed: 11/24/2022] Open
Abstract
Superoxide dismutase (SOD) is an enzyme found in most food sources, might be a candidate to reduce oxidative damage to intestinal barrier, thereby ameliorating the vicious circle between hyperglycemia and the oxidative damage. Here we report the oral administration of SOD, liposome-embedded SOD (L-SOD), and SOD hydrolysate to type 2 diabetic model rats to confirm this hypothesis. Oxidative damage severity in model rat intestine was indicated by malondialdehyde level, GSSG/GSH ratio, and antioxidant enzyme activity. The damage was significantly repaired by L-SOD. Furthermore, blood glucose and related indexes correlated well not only with oxidative damage results but also with indexes indicating physical intestinal damage such as colon density, H&E staining, immunohistochemical analysis of the tight junction proteins occludin and ZO-1 in the colon, as well as lipopolysaccharide and related inflammatory cytokine levels. The order of the magnitude of the effects of these SOD preparations was L-SOD > SOD > SOD hydrolysate. These data indicate that orally administered SOD can exhibit glucose-lowering effect via targeting the intestine of diabetic rats and systemic lipopolysaccharide influx.
Collapse
|
|
32
|
Role of an unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites. EXPERIMENTAL & MOLECULAR MEDICINE 2022; 54:1125-1132. [PMID: 35931735 PMCID: PMC9440228 DOI: 10.1038/s12276-022-00816-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 12/24/2021] [Accepted: 03/23/2022] [Indexed: 12/02/2022]
Abstract
Recent investigations have revealed that the human microbiome plays an essential role in the occurrence of type 2 diabetes (T2D). However, despite the importance of understanding the involvement of the microbiota throughout the body in T2D, most studies have focused specifically on the intestinal microbiota. Extracellular vesicles (EVs) have been recently found to provide important evidence regarding the mechanisms of T2D pathogenesis, as they act as key messengers between intestinal microorganisms and the host. Herein, we explored microorganisms potentially associated with T2D by tracking changes in microbiota-derived EVs from patient urine samples collected three times over four years. Mendelian randomization analysis was conducted to evaluate the causal relationships among microbial organisms, metabolites, and clinical measurements to provide a comprehensive view of how microbiota can influence T2D. We also analyzed EV-derived metagenomic (N = 393), clinical (N = 5032), genomic (N = 8842), and metabolite (N = 574) data from a prospective longitudinal Korean community-based cohort. Our data revealed that GU174097_g, an unclassified Lachnospiraceae, was associated with T2D (β = −189.13; p = 0.00006), and it was associated with the ketone bodies acetoacetate and 3-hydroxybutyrate (r = −0.0938 and −0.0829, respectively; p = 0.0022 and 0.0069, respectively). Furthermore, a causal relationship was identified between acetoacetate and HbA1c levels (β = 0.0002; p = 0.0154). GU174097_g reduced ketone body levels, thus decreasing HbA1c levels and the risk of T2D. Taken together, our findings indicate that GU174097_g may lower the risk of T2D by reducing ketone body levels. A microbe that may help protect against type II diabetes has been detected by examining extracellular vesicles (EVs), tiny membrane-wrapped packages secreted by human cells and by the bacteria making up the microbiome. Examining EVs allows researchers to sample microbial populations other than the intensively studied intestinal microbiome. Sungho Won, Seoul National University, and Geum-Sook Hwang, Korea Basic Science Institute, Seoul, and coworkers studied the microbial EVs in urine samples collected from South Korean subjects over four years. They identified a previously unclassified bacterial species in the family Lachnospiraceae that was associated with lower risk of developing type II diabetes. Further investigation showed that these bacteria may break down ketone bodies, metabolic byproducts that signal disrupted sugar metabolism leading to diabetes. These results contribute to understanding how the microbiome contributes to metabolic health and disease.
Collapse
|
|
33
|
Zheng L, Ji YY, Wen XL, Duan SL. Fecal microbiota transplantation in the metabolic diseases: Current status and perspectives. World J Gastroenterol 2022; 28:2546-2560. [PMID: 35949351 PMCID: PMC9254144 DOI: 10.3748/wjg.v28.i23.2546] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 03/14/2022] [Accepted: 05/07/2022] [Indexed: 02/06/2023] Open
Abstract
With the development of microbiology and metabolomics, the relationship between the intestinal microbiome and intestinal diseases has been revealed. Fecal microbiota transplantation (FMT), as a new treatment method, can affect the course of many chronic diseases such as metabolic syndrome, malignant tumor, autoimmune disease and nervous system disease. Although the mechanism of action of FMT is now well understood, there is some controversy in metabolic diseases, so its clinical application may be limited. Microflora transplantation is recommended by clinical medical guidelines and consensus for the treatment of recurrent or refractory Clostridium difficile infection, and has been gradually promoted for the treatment of other intestinal and extraintestinal diseases. However, the initial results are varied, suggesting that the heterogeneity of the donor stools may affect the efficacy of FMT. The success of FMT depends on the microbial diversity and composition of donor feces. Therefore, clinical trials may fail due to the selection of ineffective donors, and not to faulty indication selection for FMT. A new understanding is that FMT not only improves insulin sensitivity, but may also alter the natural course of type 1 diabetes by modulating autoimmunity. In this review, we focus on the main mechanisms and deficiencies of FMT, and explore the optimal design of FMT research, especially in the field of cardiometabolic diseases.
Collapse
Affiliation(s)
- Lie Zheng
- Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an 710003, Shaanxi Province, China
| | - Yong-Yi Ji
- Department of Neurology, Xi’an Hospital of Traditional Chinese Medicine, Xi’an 710021, Shaanxi Province, China
| | - Xin-Li Wen
- Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an 710003, Shaanxi Province, China
| | - Sheng-Lei Duan
- Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an 710003, Shaanxi Province, China
| |
Collapse
|
|
34
|
Singh N, Haider NB. Microbiota, Microbiome, and Retinal Diseases. Int Ophthalmol Clin 2022; 62:197-214. [PMID: 35325919 DOI: 10.1097/iio.0000000000000418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
|
|
35
|
Evidence and possible mechanisms of probiotics in the management of type 1 diabetes mellitus. J Diabetes Metab Disord 2022; 21:1081-1094. [PMID: 35673472 PMCID: PMC9167374 DOI: 10.1007/s40200-022-01006-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 02/12/2022] [Indexed: 10/19/2022]
Abstract
Abstract Type 1 diabetes mellitus (T1DM) is one of the most common chronic immune-mediated diseases. The prevalence is worldwide especially among children and young adults. The destruction of the pancreatic β-cells due to some abnormalities in the immune system characterizes T1DM. Considering the high burden of the disease and its impact on human health, researchers have made great efforts during the last decades; investigating the disease pathogenesis and discovering new strategies for its management. Fortunately, probiotics have been found as potential remedies for T1DM. This review aims to explore the potentialities of probiotics in managing T1DM and its complications. Based on the outcomes of human and animal studies carried out from 2016 to 2021, the review hopes to assess the effectiveness of probiotics in the prevention and treatment of T1DM and its complications. We first tried to explain the disease's pathogenesis, and highlighted the possible mechanisms involved in these potentialities of probiotics. We concluded that, probiotics can be used as possible therapeutic tools for the management of T1DM. Possible mechanisms of action of probiotics include; the modulation of the gut microbiota, the regulation of inflammation-related cytokines, the production of short chain fatty acids (SCFAs), and the regulation of GLP-1. However, we recommend further studies especially human trials should be carried out to investigate these potentialities of probiotics. Highlights • T1DM is highly prevalent worldwide, causing high morbidity and mortality especially among children and young adults• Gut microbiota plays a significant role in the pathogenesis of T1DM via an interconnection with the immune system• Probiotics can be used as possible therapeutic tools for the management of T1DM• Possible mechanisms of action of probiotics include the modulation of the gut microbiota, the regulation of inflammation-related cytokines, the production of SCFAs, and the regulation of GLP-1.
Collapse
|
|
36
|
Vasileva SS, Tucker J, Siskind D, Eyles D. Does the gut microbiome mediate antipsychotic-induced metabolic side effects in schizophrenia? Expert Opin Drug Saf 2022; 21:625-639. [PMID: 35189774 DOI: 10.1080/14740338.2022.2042251] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Second-generation antipsychotics (SGAs) are the most effective treatment for people with schizophrenia. Despite their effectiveness in treating psychotic symptoms, they have been linked to metabolic, cardiovascular and gastrointestinal side-effects. The gut microbiome has been implicated in potentiating symptoms of schizophrenia, response to treatment and medication-induced side effects and thus presents a novel target mediating second-generation antipsychotic-induced side effects in patients. AREAS COVERED This narrative review presents evidence from clinical and pre-clinical studies exploring the relationship between the gut microbiome, schizophrenia, second-generation antipsychotics and antipsychotic-induced side-effects. It also covers evidence for psychobiotic treatment as a potential supplementary therapy for people with schizophrenia. EXPERT OPINION The gut microbiome has the potential to mediate antipsychotic-induced side-effects in people with schizophrenia. Microbiome-focused treatments should be considered in combination with standard therapy in order to ameliorate debilitating drug-induced side effects, increase quality of life and potentially improve psychotic symptoms. Future studies should aim to collect not only microbiome data, but also metabolomic measures, dietary information and behavioral data.
Collapse
Affiliation(s)
| | - Jack Tucker
- Metro South Addiction and Mental Health Service, Metro South Health, Brisbane, Australia.,University of Queensland School of Clinical Medicine, Brisbane, Australia
| | - Dan Siskind
- Queensland Brain Institute, University of Queensland, Brisbane, Australia.,Metro South Addiction and Mental Health Service, Metro South Health, Brisbane, Australia.,University of Queensland School of Clinical Medicine, Brisbane, Australia.,Queensland Centre for Mental Health Research, Brisbane, Australia
| | - Darryl Eyles
- Queensland Brain Institute, University of Queensland, Brisbane, Australia.,Queensland Centre for Mental Health Research, Brisbane, Australia
| |
Collapse
|
|
37
|
Du Y, Neng Q, Li Y, Kang Y, Guo L, Huang X, Chen M, Yang F, Hong J, Zhou S, Zhao J, Yu F, Su H, Kong X. Gastrointestinal Autonomic Neuropathy Exacerbates Gut Microbiota Dysbiosis in Adult Patients With Type 2 Diabetes Mellitus. Front Cell Infect Microbiol 2022; 11:804733. [PMID: 35211420 PMCID: PMC8861497 DOI: 10.3389/fcimb.2021.804733] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 12/17/2021] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVE The diabetic autonomic neuropathy is one of the most common complications in type 2 diabetes mellitus (T2DM), especially gastrointestinal autonomic neuropathy (GAN), which occurs in up to 75% of patients. The study aimed to investigate the gut microbiota composition, structure, and function in T2DM patients with GAN (T2DM_GAN) and set up a link between gut microbiota and clinical characteristics of patients. METHODS DNA was extracted from fecal samples of three groups using the kit method: healthy volunteers (n = 19), the patients with T2DM (n = 76), and T2DM_GAN (n = 27). Sequencing of 16S ribosomal DNA was performed using the MiSeq platform. RESULTS According to the clinical data, higher age, lower triglyceride, and lower body mass index were the main features of patients with T2DM_GAN. The gut microbiota analysis showed that Bacteroidetes, Firmicutes, and Proteobacteria constituted the three dominant phyla in healthy individuals. In addition, the gut microbiota structure and function of T2DM_GAN patients were clearly different from that of T2DM patients. T2DM patients were characterized by Fusobacteria, Fusobacteriia, Fusobacteriales, Fusobacteriaceae, Fusobacterium, Lachnoclostridium, and Fusobacterium_mortiferum. Those gut microbiota may be involved in carotenoid and flavonoid biosyntheses. Relatively, the Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, Escherichia-Shigella, Megasphaera, Escherichia_coli, and Megasphaera_elsdenii were characteristic in the T2DM_GAN patients. Those may be involved in bacterial invasion of epithelial cells and pathogenic Escherichia coli infection. CONCLUSIONS GAN exacerbated gut microbiota dysbiosis in adult patients with T2DM. The findings indicated that phyla Fusobacteria and class Gammaproteobacteria were closely related to the occurrence of T2DM. Especially the latter may promote T2DM_GAN.
Collapse
Affiliation(s)
- Yuhui Du
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
- Endocrinology Branch, The First People’s Hospital of Yunnan Province, Kunming, China
- School of Medicine, Southern University of Science and Technology, Shenzhen, China
| | - Qiongli Neng
- Endocrinology Branch, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Yu Li
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
- School of Medicine, Southern University of Science and Technology, Shenzhen, China
| | - Yongbo Kang
- School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, China
| | - Liqiong Guo
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Xinwei Huang
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Minghui Chen
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Fan Yang
- Nutrition Department, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Jingan Hong
- Nutrition Department, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Shuai Zhou
- Neurosurgery Department, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Jianhua Zhao
- Neurosurgery Department, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Fubing Yu
- Digestive System Department, Affiliated Hospital of Yunnan University, Kunming, China
| | - Heng Su
- Endocrinology Branch, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Xiangyang Kong
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| |
Collapse
|
|
38
|
Shoemaker WR, Chen D, Garud NR. Comparative Population Genetics in the Human Gut Microbiome. Genome Biol Evol 2022; 14:evab116. [PMID: 34028530 PMCID: PMC8743038 DOI: 10.1093/gbe/evab116] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/22/2021] [Indexed: 11/13/2022] Open
Abstract
Genetic variation in the human gut microbiome is responsible for conferring a number of crucial phenotypes like the ability to digest food and metabolize drugs. Yet, our understanding of how this variation arises and is maintained remains relatively poor. Thus, the microbiome remains a largely untapped resource, as the large number of coexisting species in the microbiome presents a unique opportunity to compare and contrast evolutionary processes across species to identify universal trends and deviations. Here we outline features of the human gut microbiome that, while not unique in isolation, as an assemblage make it a system with unparalleled potential for comparative population genomics studies. We consciously take a broad view of comparative population genetics, emphasizing how sampling a large number of species allows researchers to identify universal evolutionary dynamics in addition to new genes, which can then be leveraged to identify exceptional species that deviate from general patterns. To highlight the potential power of comparative population genetics in the microbiome, we reanalyze patterns of purifying selection across ∼40 prevalent species in the human gut microbiome to identify intriguing trends which highlight functional categories in the microbiome that may be under more or less constraint.
Collapse
Affiliation(s)
- William R Shoemaker
- Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California, USA
| | - Daisy Chen
- Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California, USA
| | - Nandita R Garud
- Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California, USA
- Department of Human Genetics, University of California, Los Angeles, California, USA
| |
Collapse
|
|
39
|
Yin W, Zhang SQ, Pang WL, Chen XJ, Wen J, Hou J, Wang C, Song LY, Qiu ZM, Liang PT, Yuan JL, Yang ZS, Bian Y. Tang-Ping-San Decoction Remodel Intestinal Flora and Barrier to Ameliorate Type 2 Diabetes Mellitus in Rodent Model. Diabetes Metab Syndr Obes 2022; 15:2563-2581. [PMID: 36035516 PMCID: PMC9400815 DOI: 10.2147/dmso.s375572] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 08/16/2022] [Indexed: 04/20/2023] Open
Abstract
PURPOSE Type 2 diabetes mellitus (T2DM) is a complex genetic disease associated with genetic and environmental factors. Previous studies have shown that changes in the gut microbiota may affect the development of host metabolic diseases and promote the progression of T2DM. Tang-ping-san (TPS) decoction can effectively treat T2DM. However, its specific mechanisms must be evaluated. PATIENTS AND METHODS In the present study, we established an animal model of T2DM using a high‑fat diet (HFD) with intraperitoneal injection streptozotocin injection. RESULTS The therapeutic effect of TPS decoction on T2DM in mice was initially evaluated. TPS decoction was found to improve hyperglycemia, hyperlipidemia, insulin resistance, and pathological liver, pancreatic, and colon changes. Moreover, it reduced the pro-inflammatory cytokine levels. Based on 16SrRNA sequencing, TPS decoction reduced the Firmicutes/Bacteroidetes ratio at the phylum level. At the genus level, it increased the relative abundances of Akkermansia, Muribaculaceae, and the Eubacterium coprostanoligenes group and decreased the relative abundance of Fusobacterium, Escherichia coli, Dubosiella, and Helicobacter. CONCLUSION TPS decoction improves T2DM and liver function and reduces the risk of hyperglycemia, hyperlipidemia, insulin resistance, pathological organ changes, and inflammatory reactions. The mechanism of TPS decoction in T2DM can be correlated with the reversal of gut microbiota dysfunction and repair of the intestinal mucosal barrier.
Collapse
Affiliation(s)
- Wen Yin
- Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China
| | - Si-Qi Zhang
- Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China
| | - Wen-Lin Pang
- Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China
| | - Xiao-Jiao Chen
- Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China
| | - Jing Wen
- Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China
| | - Jiong Hou
- Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China
| | - Cui Wang
- Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China
| | - Li-Yun Song
- Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China
| | - Zhen-Ming Qiu
- Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China
| | - Peng-Tao Liang
- Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China
| | - Jia-Li Yuan
- Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China
| | - Zhong-Shan Yang
- Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China
- Correspondence: Zhong-Shan Yang; Yao Bian, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China, Tel +86-871-65919932, Email ;
| | - Yao Bian
- Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China
| |
Collapse
|
|
40
|
Lei L, Zhao N, Zhang L, Chen J, Liu X, Piao S. Gut microbiota is a potential goalkeeper of dyslipidemia. Front Endocrinol (Lausanne) 2022; 13:950826. [PMID: 36176475 PMCID: PMC9513062 DOI: 10.3389/fendo.2022.950826] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 08/26/2022] [Indexed: 11/30/2022] Open
Abstract
Dyslipidemia, as a common metabolic disease, could cause atherosclerosis, coronary heart disease, stroke and other cardio-cerebrovascular diseases. It is mainly caused by the interaction of genetic and environmental factors and its incidence has increased for several years. A large number of studies have shown that gut microbiota disorder is related to the development of dyslipidemia closely. Especially its metabolites such as short-chain fatty acids, bile acids and trimethylamine N-oxide affect dyslipidemia by regulating cholesterol balance. In this paper, we systematically reviewed the literature and used knowledge graphs to analyze the research trends and characteristics of dyslipidemia mediated by gut microbiota, revealing that the interaction between diet and gut microbiota leads to dyslipidemia as one of the main factors. In addition, starting from the destruction of the dynamic balance between gut microbiota and host caused by dyslipidemia, we systematically summarize the molecular mechanism of gut microbiota regulating dyslipidemia and provide a theoretical basis for the treatment of dyslipidemia by targeting the gut microbiota.
Collapse
Affiliation(s)
- Lirong Lei
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangzhou, China
| | - Ning Zhao
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangzhou, China
| | - Lei Zhang
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangzhou, China
| | - Jiamei Chen
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangzhou, China
| | - Xiaomin Liu
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangzhou, China
| | - Shenghua Piao
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangzhou, China
- *Correspondence: Shenghua Piao,
| |
Collapse
|
|
41
|
Liu L, Zhang J, Cheng Y, Zhu M, Xiao Z, Ruan G, Wei Y. Gut microbiota: A new target for T2DM prevention and treatment. Front Endocrinol (Lausanne) 2022; 13:958218. [PMID: 36034447 PMCID: PMC9402911 DOI: 10.3389/fendo.2022.958218] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 07/22/2022] [Indexed: 12/12/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM), one of the fastest growing metabolic diseases, has been characterized by metabolic disorders including hyperglycemia, hyperlipidemia and insulin resistance (IR). In recent years, T2DM has become the fastest growing metabolic disease in the world. Studies have indicated that patients with T2DM are often associated with intestinal flora disorders and dysfunction involving multiple organs. Metabolites of the intestinal flora, such as bile acids (BAs), short-chain fatty acids (SCFAs) and amino acids (AAs)may influence to some extent the decreased insulin sensitivity associated with T2DM dysfunction and regulate metabolic as well as immune homeostasis. In this paper, we review the changes in the gut flora in T2DM and the mechanisms by which the gut microbiota modulates metabolites affecting T2DM, which may provide a basis for the early identification of T2DM-susceptible individuals and guide targeted interventions. Finally, we also highlight gut microecological therapeutic strategies focused on shaping the gut flora to inform the improvement of T2DM progression.
Collapse
Affiliation(s)
- Lulu Liu
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Jiheng Zhang
- Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yi Cheng
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Meng Zhu
- Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zhifeng Xiao
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Guangcong Ruan
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- *Correspondence: Yanling Wei, ; Guangcong Ruan,
| | - Yanling Wei
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- *Correspondence: Yanling Wei, ; Guangcong Ruan,
| |
Collapse
|
|
42
|
Bielka W, Przezak A, Pawlik A. The Role of the Gut Microbiota in the Pathogenesis of Diabetes. Int J Mol Sci 2022; 23:ijms23010480. [PMID: 35008906 PMCID: PMC8745411 DOI: 10.3390/ijms23010480] [Citation(s) in RCA: 74] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 12/26/2021] [Accepted: 12/29/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus is a significant clinical and therapeutic problem because it can lead to serious long-term complications. Its pathogenesis is not fully understood, but there are indications that dysbiosis can play a role in the development of diabetes, or that it appears during the course of the disease. Changes in microbiota composition are observed in both type 1 diabetes (T1D) and type 2 diabetes (T2D) patients. These modifications are associated with pro-inflammation, increased intestinal permeability, endotoxemia, impaired β-cell function and development of insulin resistance. This review summarizes the role of the gut microbiota in healthy individuals and the changes in bacterial composition that can be associated with T1D or T2D. It also presents new developments in diabetes therapy based on influencing the gut microbiota as a promising method to alter the course of diabetes. Moreover, it highlights the lacking data and suggests future directions needed to prove the causal relationship between dysbiosis and diabetes, both T1D and T2D.
Collapse
|
|
43
|
Karamzin AM, Ropot AV, Sergeyev OV, Khalturina EO. Akkermansia muciniphila and host interaction within the intestinal tract. Anaerobe 2021; 72:102472. [PMID: 34743983 DOI: 10.1016/j.anaerobe.2021.102472] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 10/26/2021] [Accepted: 10/27/2021] [Indexed: 02/07/2023]
Abstract
In the modern world, metabolic syndrome is one of the major health problems. Heredity, overeating, and a sedentary lifestyle are believed to be the main predisposing factors for its development. However, recent data indicate that gut microbiota plays a significant role in metabolic profile formation. In 2004, Derrien et al. isolated and characterized the bacterium Akkermansia muciniphila, which lives mainly in the human intestine and has the ability to utilize intestinal mucin. It proved to be a good candidate for the role of a new-generation probiotic due to its ability to improve the laboratory and physical indicators associated with metabolic syndrome and type 2 diabetes in mice and humans. In this review, we describe the basic microbiological characteristics of this bacterium, its main habitats, clinical effects after oral administration, and different ways of influencing the digestive tract. All these data allow us to understand the mechanism of its beneficial effects, which is important for its future introduction into the treatment of the metabolic syndrome.
Collapse
Affiliation(s)
- Andrei M Karamzin
- Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Street, 8, Moscow, Russian Federation.
| | - Anastasiia V Ropot
- Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Street, 8, Moscow, Russian Federation.
| | - Oleg V Sergeyev
- Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Street, 8, Moscow, Russian Federation.
| | - Evgenia O Khalturina
- Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Street, 8, Moscow, Russian Federation.
| |
Collapse
|
|
44
|
Alagiakrishnan K, Halverson T. Holistic perspective of the role of gut microbes in diabetes mellitus and its management. World J Diabetes 2021; 12:1463-1478. [PMID: 34630900 PMCID: PMC8472496 DOI: 10.4239/wjd.v12.i9.1463] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/24/2021] [Accepted: 08/13/2021] [Indexed: 02/06/2023] Open
Abstract
The gut microbiota (GM) plays a role in the development and progression of type 1 and type 2 diabetes mellitus (DM) and its complications. Gut dysbiosis contributes to the pathogenesis of DM. The GM has been shown to influence the efficacy of different antidiabetic medications. Intake of gut biotics, like prebiotics, probiotics and synbiotics, can improve the glucose control as well as the metabolic profile associated with DM. There is some preliminary evidence that it might even help with the cardiovascular, ophthalmic, nervous, and renal complications of DM and even contribute to the prevention of DM. More large-scale research studies are needed before wide spread use of gut biotics in clinical practice as an adjuvant therapy to the current management of DM.
Collapse
Affiliation(s)
| | - Tyler Halverson
- Department of Medicine, University of Alberta, Edmonton T6G 2G3, Alberta, Canada
| |
Collapse
|
|
45
|
Vallianou N, Dalamaga M, Stratigou T, Karampela I, Tsigalou C. Do Antibiotics Cause Obesity Through Long-term Alterations in the Gut Microbiome? A Review of Current Evidence. Curr Obes Rep 2021; 10:244-262. [PMID: 33945146 PMCID: PMC8093917 DOI: 10.1007/s13679-021-00438-w] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/21/2021] [Indexed: 02/08/2023]
Abstract
PURPOSE OF REVIEW In this review, we summarize current evidence on the association between antibiotics and the subsequent development of obesity through modulation of the gut microbiome. Particular emphasis is given on (i) animal and human studies and their limitations; (ii) the reservoir of antibiotics in animal feed, emerging antibiotic resistance, gut dysbiosis, and obesity; (iii) the role of infections, specifically viral infections, as a cause of obesity; and (iv) the potential therapeutic approaches other than antibiotics to modulate gut microbiome. RECENT FINDINGS Overall, the majority of animal studies and meta-analyses of human studies on the association between antibiotics and subsequent development of obesity are suggestive of a link between exposure to antibiotics, particularly early exposure in life, and the development of subsequent obesity as a result of alterations in the diversity of gut microbiota. The evidence is strong in animal models whereas evidence in humans is inconclusive requiring well-designed, long-term longitudinal studies to examine this association. Based on recent meta-analyses and epidemiologic studies in healthy children, factors, such as the administration of antibiotics during the first 6 months of life, repeated exposure to antibiotics for ≥ 3 courses, treatment with broad-spectrum antibiotics, and male gender have been associated with increased odds of overweight/obesity. Early antibiotic exposure in animal models has shown that reductions in the population size of specific microbiota, such as Lactobacillus, Allobaculum, Rikenellaceae, and Candidatus Arthromitus, are related to subsequent adiposity. These data suggest that the loss of diversity of the gut microbiome, especially early in life, may have potential long-term detrimental effects on the adult host gut microbiome and metabolic health. Genetic, environmental, and age-related factors influence the gut microbiome throughout the lifetime. More large-scale, longer-term, longitudinal studies are needed to determine whether changes that occur in the microbiome after exposure to antibiotics, particularly early exposure, are causal of subsequent weight gain or consequent of weight gain in humans. Further well-designed, large-scale RCTs in humans are required to evaluate the effects of administration of antibiotics, particularly early administration, and the subsequent development of overweight/obesity. Therapeutic interventions, such as bacteriophage treatment or the use of probiotics, especially genetically engineered ones, need to be evaluated in terms of prevention and management of obesity.
Collapse
Affiliation(s)
- Natalia Vallianou
- grid.414655.70000 0004 4670 4329Department of Internal Medicine and Endocrinology, ‘Evangelismos’ General Hospital of Athens, 45-47 Ypsilantou Street, 10676 Athens, Greece
| | - Maria Dalamaga
- grid.5216.00000 0001 2155 0800Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527 Athens, Greece
| | - Theodora Stratigou
- grid.414655.70000 0004 4670 4329Department of Internal Medicine and Endocrinology, ‘Evangelismos’ General Hospital of Athens, 45-47 Ypsilantou Street, 10676 Athens, Greece
| | - Irene Karampela
- grid.5216.00000 0001 2155 0800Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527 Athens, Greece
- grid.5216.00000 0001 2155 0800Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini St, Haidari, 12462 Athens, Greece
| | - Christina Tsigalou
- grid.12284.3d0000 0001 2170 8022Laboratory of Microbiology, Medical School, Democritus University of Thrace, 6th Km Alexandroupolis-Makri, Alexandroupolis, Greece
| |
Collapse
|
|
46
|
Abstract
Anthropogenic environmental pollutants affect many physiological, biochemical, and endocrine actions as reproduction, metabolism, immunity, behavior and as such can interfere with any aspect of hormone action. Microbiota and their genes, microbiome, a large body of microorganisms, first of all bacteria and co-existing in the host´s gut, are now believed to be autonomous endocrine organ, participating at overall endocrine, neuroendocrine and immunoendocrine regulations. While an extensive literature is available on the physiological and pathological aspects of both players, information about their mutual relationships is scarce. In the review we attempted to show various examples where both, endocrine disruptors and microbiota are meeting and can act cooperatively or in opposition and to show the mechanism, if known, staying behind these actions.
Collapse
Affiliation(s)
- R Hampl
- Institute of Endocrinology, Prague, Czech Republic.
| | | |
Collapse
|
|
47
|
Xia F, Wen LP, Ge BC, Li YX, Li FP, Zhou BJ. Gut microbiota as a target for prevention and treatment of type 2 diabetes: Mechanisms and dietary natural products. World J Diabetes 2021; 12:1146-1163. [PMID: 34512884 PMCID: PMC8394227 DOI: 10.4239/wjd.v12.i8.1146] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 05/10/2021] [Accepted: 07/05/2021] [Indexed: 02/06/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is among the most remarkable public health concerns globally. Accumulating research evidence documents that alteration of gut microbiota has an indispensable role in the onset and progression of obesity and T2DM. A reduced microbial diversity is linked to insulin resistance and energy metabolism, especially for the rise of the Firmicutes/Bacteroidetes ratio. Changes in metabolites followed by the gut dysbacteriosis are linked to the presence of T2DM. Moreover, endotoxin leakage and gut permeability caused by gut dysbacteriosis is more of a trigger for the onset and progression of T2DM. Research documents that natural products are remarkable arsenals of bioactive agents for the discovery of anti-T2DM drugs. Many studies have elucidated that the possible mechanisms of the anti-T2DM effects of natural products are remarkably linked to its regulation on the composition of gut microflora and the successive changes in metabolites directly or indirectly. This review presents a brief overview of the gut microbiota in T2DM and several relevant mechanisms, including short-chain fatty acids, biosynthesis and metabolism of branched-chain fatty acids, trimethylamine N-oxide, bile acid signaling, endotoxin leakage, and gut permeability, and describes how dietary natural products can improve T2DM via the gut microbiota.
Collapse
Affiliation(s)
- Fan Xia
- Department of Pharmacy, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, Guangdong Province, China
| | - Lu-Ping Wen
- Department of Pharmacy, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, Guangdong Province, China
| | - Bing-Chen Ge
- Department of Pharmacy, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, Guangdong Province, China
| | - Yu-Xin Li
- Department of Pharmacology, Guangdong Medical University, Zhanjiang 524023, Guangdong Province, China
| | - Fang-Ping Li
- Department of Endocrinology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, Guangdong Province, China
| | - Ben-Jie Zhou
- Department of Pharmacy, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, Guangdong Province, China
| |
Collapse
|
|
48
|
Hu Y, He J, Zheng P, Mao X, Huang Z, Yan H, Luo Y, Yu J, Luo J, Yu B, Chen D. Prebiotic inulin as a treatment of obesity related nonalcoholic fatty liver disease through gut microbiota: a critical review. Crit Rev Food Sci Nutr 2021; 63:862-872. [PMID: 34292103 DOI: 10.1080/10408398.2021.1955654] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The microbial-derived products, including short chain fatty acids, lipopolysaccharide and secondary bile acids, have been shown to participate in the regulation of hepatic lipid metabolism. Previous studies have demonstrated that prebiotics, such as oligosaccharide and inulin, have abilities to change the concentration of microbial-derived products through modulating the microbial community structure, thus controlling body weight and alleviating hepatic fat accumulation. However, recent evidence indicates that there are individual differences in host response upon inulin treatment due to the differences in host microbial composition before dietary intervention. Probably it is because of the multiple relationships among bacterial species (e.g., competition and mutualism), which play key roles in the degradation of inulin and the regulation of microbial structure. Thereby, analyzing the composition and function of initial gut microbiota is essential for improving the efficacy of prebiotics supplementation. Furthermore, considering that different structures of polysaccharides can be used by different microorganisms, the chemical structure of processed inulin should be tested before using prebiotic inulin to treat obesity related nonalcoholic fatty liver disease.
Collapse
Affiliation(s)
- Yaolian Hu
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Jun He
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Ping Zheng
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Xiangbing Mao
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Zhiqing Huang
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Hui Yan
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Yuheng Luo
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Jie Yu
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Junqiu Luo
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Bing Yu
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Daiwen Chen
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| |
Collapse
|
|
49
|
Li Y, Tan Y, Xia G, Shuai J. Effects of probiotics, prebiotics, and synbiotics on polycystic ovary syndrome: a systematic review and meta-analysis. Crit Rev Food Sci Nutr 2021; 63:522-538. [PMID: 34287081 DOI: 10.1080/10408398.2021.1951155] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
This meta-analysis of randomized controlled trials (RCTs) was performed to summarize the effects of probiotics, prebiotics, and synbiotics on insulin resistance (IR), lipid profiles, anthropometric indices, and C-reactive protein (CRP) level for polycystic ovary syndrome (PCOS). We searched 8 databases from their inception until 1st October, 2020. The effect sizes were expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Subgroup analyses were undertaken for further identification of effects of probiotics, prebiotics, and synbiotics, based on the following aspects: (1) type of intervention (probiotics, prebiotics, or synbiotics); (2) study duration (≥ 12 weeks or < 12 weeks); (3) number of probiotic strains (multi strains or single strain); (4) probiotic dose (≥ 2 × 108 colony-forming units [CFU] or < 2 × 108 CFU). A total of 17 eligible RCTs with 1049 participants were included. Results showed that probiotic, prebiotic, and synbiotic intake decreased fasting plasma glucose (SMD, -1.35; 95% CI, -2.22 to -0.49; p = 0.002), fasting insulin (SMD, -0.68; 95% CI, -1.08 to -0.27; p = 0.001), homeostatic model of assessment for IR (SMD, -0.73; 95% CI, -1.15 to -0.31; p = 0.001), triglycerides (SMD, -0.85; 95% CI, -1.59 to -0.11; p = 0.024), total cholesterol (SMD, -1.09; 95% CI, -1.98 to -0.21; p = 0.015), low-density lipoprotein cholesterol (SMD, -0.84; 95% CI, -1.64 to -0.03; p = 0.041), very-low-density lipoprotein cholesterol (SMD, -0.44; 95% CI, -0.70 to -0.18; p = 0.001), and increased quantitative insulin sensitivity check index (SMD, 2.00; 95% CI, - 0.79 to 3.22; p = 0.001). However, probiotic, prebiotic, and synbiotic supplements did not affect anthropometric indices, high-density lipoprotein cholesterol, and CRP levels. Subgroup analysis showed that probiotic or prebiotic might be the optimal choice for ameliorating IR or lipid profiles, respectively. Additionally, the effect was positively related to courses and therapeutical dose. Overall, the meta-analysis demonstrates that probiotic, prebiotic, or synbiotic administration is an effective and safe intervention for modifying IR and lipid profiles.
Collapse
Affiliation(s)
- Yuling Li
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.,Nanjing University of Chinese Medicine, Nanjing, China
| | - Yong Tan
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.,Nanjing University of Chinese Medicine, Nanjing, China
| | - Guicheng Xia
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.,Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiaqi Shuai
- Masaryk University, Brno, The Czech Republic
| |
Collapse
|
|
50
|
Zakrzewski M, Gannon OM, Panizza BJ, Saunders NA, Antonsson A. Human papillomavirus infection and tumor microenvironment are associated with the microbiota in patients with oropharyngeal cancers-pilot study. Head Neck 2021; 43:3324-3330. [PMID: 34278648 DOI: 10.1002/hed.26821] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 06/07/2021] [Accepted: 07/09/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Previous microbiome studies of oropharyngeal cancer have shown that there are differences in the oral microbiota between human papillomavirus (HPV)-positive and HPV-negative patients. METHODS We collected saliva, normal tissue, and tumor biopsies from 13 patients with oropharyngeal cancer (eight HPV-positive, five HPV-negative). We obtained basic clinical data from each patient. Extracted DNA was 16S rRNA gene sequenced. Analysis was based on HPV status and sample site using univariate, multivariate, and mixed effect regression methods. RESULTS Multivariate analysis methods separated samples based on HPV status (Adonis, p < 0.001). Comparison of patients showed that there were significant changes in microbial richness across all sites based on HPV status (linear mixed effects regression, p = 0.0002). CONCLUSIONS We found significant differences in overall microbial community and bacterial richness between oropharyngeal patients based on HPV status. Our results suggest that there are significant differences in the microbiome in patients with oropharyngeal cancer based on HPV status.
Collapse
Affiliation(s)
- Martha Zakrzewski
- Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
| | - Orla Margaret Gannon
- The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia
| | - Benedict James Panizza
- Department of Otolaryngology - Head and Neck Surgery, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Nicholas Andrew Saunders
- The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia
| | - Annika Antonsson
- Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.,Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
| |
Collapse
|