The pathogenesis of cancer is closely related to the disruption of homeostasis in the human body. The gut microbiome plays crucial roles in maintaining the homeostasis of its host throughout lifespan. In recent years, a large number of studies have shown that dysbiosis of the gut microbiome is involved in the entire process of cancer initiation, development, and prognosis by influencing the host immune system and metabolism. Some specific intestinal bacteria promote the occurrence and development of cancers under certain conditions. Conversely, some other specific intestinal bacteria suppress the oncogenesis and progression of cancers, including inhibiting the occurrence of cancers, delaying the progression of cancers and boosting the therapeutic effect on cancers. The promoting effects of the gut microbiome on cancers have been comprehensively discussed in the previous review. This article will review the latest advances in the roles and mechanisms of gut microbiome in cancer suppression, providing a new perspective for developing strategies of cancer prevention and treatment.

In order to study the distribution characteristics of intestinal microbiota and antibiotic resistance genes (ARGs) in Duzang pigs after adding stems and leaves of Panax notoginseng to the feed, the characteristics of intestinal microbiota were explored by metagenomic sequencing, and 14 ARGs and 2 integrase genes were detected by qPCR. The results showed that the addition of stems and leaves of P. notoginseng increased the relative abundance of Firmicutes, Lactobacillus and Pediococcus in the cecum of Duzang pigs. A total of 10 ARGs and 2 integrase genes were detected in the cecal contents of pigs. The addition of stems and leaves of P. notoginseng reduced the relative abundance of total ARGs, ermB, tetO and tetW in the cecum of Duzang pigs. The results of network analysis showed that multiple genera were potential hosts of ARGs. The addition of stems and leaves of P. notoginseng may reduce the relative abundance of ARGs by reducing the relative abundance of genera such as Corynebacterium and Flavonifractor, thereby reducing the risk of ARGs spread. This study provides a theoretical basis for the rational use of stems and leaves of P. notoginseng to control ARGs.

Roseburia intestinalis is one of the most abundant and important butyrate-producing human gut anaerobic bacteria that plays an important role in maintaining health and is a potential next-generation probiotic. We investigated the pangenome of 16 distinct strains, isolated over several decades, identifying local and time-specific adaptations. More than 50% of the genes in each individual strain were assigned to the core genome, and 77% of the cloud genes were unique to individual strains, revealing the high level of genome conservation. Co-carriage of the same enzymes involved in carbohydrate binding and degradation in all strains highlighted major pathways in carbohydrate utilization and reveal the importance of xylan, starch and mannose as key growth substrates. A single strain had adapted to use rhamnose as a sole growth substrate, the first time this has been reported. The ubiquitous presence of motility and sporulation gene clusters demonstrates the importance of these phenotypes for gut survival and acquisition of this bacterium. More than half the strains contained functional, potentially transferable, tetracycline resistance genes. This study advances our understanding of the importance of R. intestinalis within the gut ecosystem by elucidating conserved metabolic characteristics among different strains, isolated from different locations. This information will help to devise dietary strategies to increase the abundance of this species providing health benefits.

Despite extensive investigations into the microbiome and metabolome changes associated with colon polyps and colorectal cancer (CRC), the microbiome and metabolome profiles of individuals with colonic polyposis, including those with (Gene-pos) and without (Gene-neg) a known genetic driver, remain comparatively unexplored. Using colon biopsies, polyps, and stool from patients with Gene-pos adenomatous polyposis (N = 9), Gene-neg adenomatous polyposis (N = 18), and serrated polyposis syndrome (SPS, N = 11), we demonstrated through 16S rRNA sequencing that the mucosa-associated microbiota in individuals with colonic polyposis is representative of the microbiota associated with small polyps, and that both Gene-pos and SPS cohorts exhibit differential microbiota populations relative to Gene-neg polyposis cohorts. Furthermore, we used these differential microbiota taxa to perform linear discriminant analysis to differentiate Gene-neg subjects from Gene-pos and from SPS subjects with an accuracy of 89% and 93% respectively. Stool metabolites were quantified via 1H NMR, revealing an increase in alanine in SPS subjects relative to non-polyposis subjects, and Partial Least Squares Discriminant Analysis (PLS-DA) analysis indicated that the proportion of leucine to tyrosine in fecal samples may be predictive of SPS. Use of these microbial and metabolomic signatures may allow for better diagnostric and risk-stratification tools for colonic polyposis patients and their families as well as promote development of microbiome-targeted approaches for polyp prevention.

The intratumoral microbiota plays a critical role in lung cancer development, metastasis, and treatment response, offering valuable insights into the tumor microenvironment (TME) and revealing new therapeutic opportunities. Lung cancer remains the leading cause of cancer-related deaths worldwide, with the intratumoral microbiota exhibiting unique characteristics and functions within this disease. In this review, we summarized the origin of the intratumoral microbiota, its entry into the tumor, its detailed composition, functions, and its potential clinical applications in lung cancer. For the first time, we estimate the absolute abundance of different microbes in lung cancer, highlight the specific differences in microorganisms, and track their dynamic changes from health to disease. We also describe the overall landscape of intratumoral microbiota. Finally, we discuss the challenges and implications of this emerging field, offering insights for future research and therapeutic strategies.

The evidence suggests that the microbiome plays a crucial role in cancer development. The oral cavity has many microorganisms that can influence oral cancer progression. Understanding the mechanisms and signaling pathways of the oral, gum, and teeth microbiome in tumor progression can lead to new treatment strategies. Probiotics, which are friendly microorganisms, have shown potential as anti-cancer agents. These positive characteristics of probiotic strains make them suitable for cancer prevention or treatment. The oral-gut microbiome axis supports health and homeostasis, and imbalances in the oral microbiome can disrupt immune signaling pathways, epithelial barriers, cell cycles, apoptosis, genomic stability, angiogenesis, and metabolic processes. Changes in the oral microbiome in oral cancer may suggest using probiotics-based treatments for their direct or indirect positive roles in cancer development, progression, and metastasis, specifically oral squamous cell carcinoma (OSCC). Here, reported relationships between probiotics, oral microbiota, and oral cancer are summarized.

Milk has high risk for microbial contamination. RSQ01, a bacteriocin, previously has shown potentiality for pasteurized milk preservation. This study analyzed the effects of RSQ01 on milk microbiota by comparison of bacterial number and composition in 3 pasteurized milk groups: controls without RSQ01, treatment group with the addition of 2× MIC (low concentration), and treatment group with the addition of 4× MIC RSQ01 (high concentration). Integrated 16S ribosomal DNA sequencing and metagenomics of these groups after 3 d of storage showed inhibition of RSQ01 on microbiota diversity. Pathogenic bacteria such as Salmonella showed a decrease in relative abundance after RSQ01 treatment, whereas probiotic bacteria such as Lactococcus showed an increase, indicating that RSQ01 contributed to milk preservation by maintaining a low abundance of pathogens and a relatively high abundance of probiotics. Further investigations revealed that milk preservation was primarily attributed to the ability of RSQ01 to decrease the relative abundance of genes related to metabolism of energy and nutrients (e.g., vitamins, lipids, and AA) of microbiota, with change of genetic, environmental, and cellular processes. Interestingly, RSQ01 generally reduced the relative abundance of virulence factors and quorum-sensing-related genes in microbiota, likely reducing virulence and resistance. The findings provided insights into microbiomics mechanisms regarding pasteurized milk preservation of bacteriocins.

Gastric cancer arises from complex carcinogenic factor interactions, with limited treatment options due to the lack of targetable driver gene mutations and significant tumor heterogeneity. Recent studies have provided promising novel approaches to improve our understanding of gastric cancer heterogeneity through integrated characterization, combining genomics with emerging technologies. Delineating the molecular changes and targeting specific molecular subtypes will enhance the efficacy of gastric cancer treatment and improve clinical outcomes. This review provides a comprehensive overview of current technologies used in gastric cancer research, highlighting key discoveries and treatment strategies driven by these innovations. Finally, we discuss the emerging technology-guided directions and potential breakthroughs that could enhance the understanding of gastric cancer tumor heterogeneity, ultimately improving clinical outcomes.

There is a widely known relationship between certain microbes and cancer progression. For instance, Helicobacter pylori is associated with the occurrence of gastric cancer, while HPV is associated with cervical and head and neck cancers. Recent studies have uncovered novel and important associations between bacterial presence and tumor formation and treatment response. Apart from the influence of the intestinal microbiome on cancer, the local activity of bacteria affects disease properties as well. Bacteria can localize within tumors in less vascularized niches. Their presence mediates the activity of signaling pathways, which contribute to tumorigenesis. Furthermore, they affect the composition of the tumor microenvironment, a highly complex structure composed of immunoregulatory cells and secreted inflammatory mediators. Recently, researchers have analyzed the properties of bacteria to develop novel anticancer strategies. The aim of this review is to discuss the latest findings regarding the relationships between bacteria and cancer and the properties of bacteria that could be used to kill cancer cells.

Muscle health is crucial, especially for aging populations. This study investigates how plant protein and probiotic supplementation in a low-protein (LP) diet affects the gut microbiota, metabolome, and muscle health in aging SAMP8 mice, emphasizing the gut-muscle axis in older populations. Twenty-four 8-month-old male SAMP8 mice were divided into four groups: control (CON, standard diet), low-protein (LP), LP supplemented with plant protein (LP + P), and LP supplemented with plant protein and probiotics (LP + P + B). The experimental treatment lasted 8 weeks. Results showed that, by week 6, body weight increased significantly in all LP groups, with a trend toward higher body fat. Protein utilization and muscle strength improved significantly in the supplemented groups compared to the LP group (P < 0.05). The LP group showed elevated levels of inflammatory cytokines (IL-12p70, IL-6, TNF-α) (P < 0.05) in serum, which were reduced in the supplemented groups, especially in the LP + P + B group (P < 0.05). Gene expression related to muscle protein synthesis (mTOR, S6K1) and oxidative stress (CAT, Nrf2) was upregulated in the LP group but downregulated in the supplemented groups (P < 0.05). Immune-related genes followed similar patterns, with inflammation markers being significantly reduced after supplementation (P < 0.05). After supplementation, fecal beneficial bacteria (Bifidobacterium, Roseburia) and metabolites (butyric acid, indole-3-propionic acid, kyotorphin) increased, indicating enhanced gut health (P < 0.05). Specific bacterial species were correlated with metabolites and immune markers, highlighting their role in immune modulation (P < 0.05). These results show that supplementing plant protein and probiotics into an LP diet improved muscle strength, reduced inflammation, optimized gut microbiota, and boosted beneficial metabolism. The findings suggest that plant protein and probiotics can maintain muscle health and regulate immune responses in the elderly.

Maize (Zea mays L.), as a globally significant food and economic crop, has attracted considerable attention from both the academic and industrial sectors due to its rich nutrient components and wide-ranging application value. In recent years, maize oligosaccharides have exhibited remarkable bioactivities in regulating gut microbiota, lowering blood glucose levels, and improving lipid metabolism, thus emerging as a research hotspot. Numerous scholars have conducted relatively in-depth studies on maize oligosaccharides. However, the relevant research findings are fragmented, lacking a systematic summary, which is detrimental to their high-value-added development and utilization. In view of this, this study intends to systematically review the research progress of maize oligosaccharides in aspects such as extraction, separation and purification, structural characterization, bioactivity, and application, analyze the existing problems and deficiencies, and put forward suggestions for future research directions. The aim is to provide theoretical support for the in-depth development and application of maize oligosaccharides and promote their high-value-added development in fields such as food, pharmaceuticals, and health products.

The growing crisis of antibiotic resistance and the increasing incidence of cancer have prompted the exploration of innovative approaches, such as gene editing and antimicrobial peptides (AMPs). The human microbiome is integral to various aspects of health, disease, and therapeutic development, influencing metabolic pathways, immune function, and pathogen resistance. Recent advances in gene editing technologies, particularly CRISPR (clustered regularly interspaced short palindromic repeats), have opened new avenues for leveraging the microbiome to address complex medical challenges, including combating multidrug-resistant pathogens and cancer. The microbiome plays a crucial role in combating antibiotic resistance by modulating microbial communities, influencing pathogen survival and susceptibility to treatments. This review explores the microbiome's dynamic role in metabolic regulation, its contribution to cancer management, and how AMPs help maintain homeostasis and exhibit emerging anticancer properties, supported by both preclinical findings and clinical evidence. Additionally, CRISPR-based microbiome engineering offers potential to enhance host-microbiome interactions, optimizing therapeutic outcomes. The integration of microbiome metagenomics and proteomics has led to the discovery of novel AMPs with targeted anticancer effects. Innovative strategies, such as engineered probiotics and CRISPR-based microbiome engineering, present exciting prospects for next-generation therapies. Despite these advances, the translation of microbiome-based therapies into clinical settings remains challenging due to ethical, regulatory, and ecological hurdles. This review underscores the transformative potential of microbiome-based interventions, emphasizing the role of personalized medicine in maximizing therapeutic efficacy. Furthermore, we also address critical research gaps, limitations, and future directions, including optimizing AMP stability, delivery, and bioavailability, as well as overcoming the regulatory and ethical challenges in clinical translation.

Intestinal microbiota is a complex ecosystem of microorganisms that perform diverse metabolic activities to maintain gastrointestinal homeostasis. These microorganisms provide energy and nutrients for growth and reproduction while producing numerous metabolites including lipopolysaccharides (LPS), Bacteroides fragilis toxin (BFT), bile acids (BAs), polyamines (PAs), and short-chain fatty acids (SCFAs). These metabolites are linked to inflammation and various metabolic diseases, such as obesity, type-2 diabetes, non-alcoholic fatty liver disease, cardiometabolic disease, and malnutrition. In addition, they may contribute to tumorigenesis. Evidence suggests that these microbes can increase the susceptibility to certain cancers and affect treatment responses. In this review, we discuss the current knowledge on how the gut microbiome and its metabolites influence tumorigenesis, highlighting the potential molecular mechanisms and prospects for basic and translational research in this emerging field.

Colorectal cancer (CRC) is the third most frequent cancer worldwide. Despite advances in treatment, conventional chemotherapy suffers from severe side effects and limited drug selectivity, highlighting the importance of alternative therapies. In this study, a polymer-lipid hybrid microcarrier was developed for oral co-administration of paclitaxel (PTX) and tributyrin (TB) as a novel approach for CRC therapy. The microcarrier was designed with a pH-sensitive polymeric shell that encapsulates drug-loaded nanostructured lipid carriers (NLC); shell dissolution at intestinal pH enables localized release of the NLC. The methodological approach employed an emulsion of vegetable oil and NLC as a template for polymer deposition. Multiple parameters were optimized, including polymers ratios, NLC dilution, acid concentration, and sonication time. Spherical hybrid particles with smooth surface and mean size of 1000 nm were obtained; PTX encapsulation efficiency was 99.9 ± 0.2 %, with a production yield of 97.2 ± 0.08 %. Drug release followed the Korsmeyer-Peppas kinetic model. Cytotoxic evaluation in human colorectal adenocarcinoma HCT-116 monolayers showed that PTX encapsulation increased cytotoxicity, lowering IC50 to 83.7 nM compared to 199.5 nM for free PTX. The addition of TB further improved cytotoxicity, reducing the IC50 to 60.8 nM. A similar potentiation cytotoxicity was observed in spheroids. The microcarrier induced reductions in colony formation, alterations in cell cytoskeleton, and led to a significant reduction in P-glycoprotein expression compared to its free form, suggesting its potential to help to overcome drug resistance. These results point to the promising applicability of the hybrid microcarrier as an innovative delivery system for oral administration of cytotoxic agents.

Necrotic enteritis (NE), caused by Clostridium perfringens, has seen a surge in chicken populations recently due to the ban on antibiotic growth promoters in feed.

In this research, screening and identification of probiotics with strong antagonistic ability against C. perfringens from 34 wild bird fecal isolates, followed by analysis of probiotic characteristics and carbon source metabolic activity. Strains exhibiting favorable antagonistic activity against C. perfringens were subsequently employed in vivo study to evaluate their protective efficacy against C. perfringens challenge in locally-sourced broilers.

The results showed that Enterococcus faecalis strains YL-EF25 and YL-EF32 were selected based on their ability to inhibit the growth and biofilm formation of C. perfringens. These two strains demonstrated good tolerance to bile salts, artificial gastric juice, and phenol, as well as metabolic activity toward dietary fiber and propionic acid precursor substances. In vivo tests on locally-sourced broilers revealed that NE induced body weight loss, intestinal lesions, and intestinal inflammation, as well as imbalance in the gut microflora. Administration of E. faecalis YL-EF25 and YL-EF32 can alleviate these symptoms. We find that feed supplementation with YL-EF25 and YL-EF32 reduced the lesion score of challenged chicks (p < 0.05), with increased tight junction-related gene expression (Occludin and ZO-1) and decreased proinflammatory cytokine (TNF-α and IFN-γ) expression in jejunum compared with NE-induced broilers (p < 0.05). Furthermore, E. faecalis YL-EF25 can boost peripheral blood lymphocyte proliferation activity (p < 0.05).

These finding indicated that addition of E. faecalis YL-EF25 and YL-EF32 improved growth performance and mitigated NE-induced gut injury, possibly by strengthening intestinal mucosal barrier function and restoring effects on the ileal microbial composition in C. perfringens-challenged broilers.

Short-chain fatty acids (SCFAs) are a group of organic compounds produced by the fermentation of dietary fibre by the human gut microbiota. They play diverse roles in different physiological processes of the host with implications for human health and disease. This Review provides an overview of the complex microbial metabolism underlying SCFA formation, considering microbial interactions and modulating factors of the gut environment. We explore the multifaceted mechanistic interactions between SCFAs and the host, with a particular focus on the local actions of SCFAs in the gut and their complex interactions with the immune system. We also discuss how these actions influence intestinal and extraintestinal diseases and emerging therapeutic strategies using SCFAs.

In the last twenty years, epidemiological research has suggested a potential decreased susceptibility to cancer among individuals diagnosed with Parkinson's disease (PD), although conflicting findings exist regarding the connection between PD and Colorectal cancer (CRC). This systematic review and meta-analysis were conducted to investigate the contemporary epidemiological data on the risk of CRC in PD.

A comprehensive search of the literature was conducted utilizing three databases: PubMed, Scopus, and Web of Science. We included observational studies (cross-sectional, case-control, and cohort) that examined the relationship between PD and CRC. We also analyzed data obtained from the Parkinson's Progression Markers Initiative (PPMI) to evaluate the frequency of CRC among individuals diagnosed with PD, control participants, and PD patients carrying the LRRK2 genetic variant.

We included 22 studies with a total of 1,3137,089 PD cases were included in our study. Our analysis demonstrated a significant relationship between PD and a reduced incidence of CRC (pooled RR = 0.80, 95% CI = 0.69-0.91). Subgroup analysis based on study design revealed a significant association in the cohort (pooled RR = 0.80, 95% CI = 0.66-0.93) and case-control studies (pooled RR = 0.77, 95% CI = 0.66-0.89). Also, sub-group analysis based on the study continent showed no significant association in North America (pooled RR = 0.83, 95% CI = 0.51-1.18, and Asia (pooled RR = 0.85, 95% CI = 0.55-1.15). However, analysis based on continents indicated significant results solely in Europe (pooled RR = 0.79, 95% CI = 0.71-0.86). PPMI analysis revealed distinct differences in CRC frequencies across the three groups (p < 0.001) with PD patients with LRRK2 genetic variant exhibited the highest frequency of colorectal cancer, followed closely by healthy subjects.

In conclusion, our study demonstrates a decreased risk of CRC in individuals with PD, suggesting an inverse association between the two diseases. Further research is warranted to elucidate the underlying mechanisms driving this correlation, paving the way for the development of targeted strategies for the prevention and management of both PD and CRC.

Inflammatory Bowel Disease (IBD) is a complex intestinal disorder that typically triggers inflammatory responses, immune dysregulation, and gut microbiota imbalance. Lignoformic acid (LFA) is a lignin-derived compound containing benzene rings and hydroxyl functional groups. It has antioxidant properties and can regulate intestinal pH. This study aimed to investigate the improve effects of LFA on dextran sulfate sodium (DSS)-induced chronic colitis in mice. The results showed that LFA treatment significantly improved body weight and Disease Activity Index (DAI) in mice and alleviated colon damage. In terms of oxidative stress and anti-inflammatory effects, the expression of antioxidant enzymes such as Glutathione Peroxidase (GSH-PX) and Superoxide Dismutase (SOD) was dose-dependently enhanced in DSS-induced mice. LFA reduced the expression of Tumor Necrosis Factor-alpha (TNF-α) by modulating the TLR4/MyD88/NF-κB signaling pathway. Furthermore, LFA dose-dependently increased the abundance of beneficial bacteria, including Akkermansia and Lachnospiraceae, and promoted the production of short-chain fatty acids (SCFAs). These findings suggest that LFA could serve as a therapeutic agent for colitis by enhancing intestinal barrier integrity, regulating inflammation, and restoring gut microbiota balance.

Diarrheal diseases remain a major public health concern, particularly in regions with poor sanitation. Polysaccharides extracted from natural gums have been investigated as functional agents for intestinal health, and their fractionation enables the production of oligosaccharides with potential prebiotic activity. This study aimed to produce cashew gum (CG) fractions through Smith degradation (CGD48) and partial hydrolysis (CGD24) and to evaluate their ability to modulate and protect the intestinal microbiota. Balb/c mice were administered CG (1200 mg/kg), CGD24 (800 mg/kg), or CGD48 (800 mg/kg) for 10 and 26 days, followed by infection with Shiga toxin-producing Escherichia coli (STEC) (5 × 1010 CFU/mL) for three days. Characterization assays confirmed the fragmentation of CG. Both CGD24 and CGD48 promoted the growth of beneficial bacteria with and without infection and reduced STEC colonization. Furthermore, they preserved mucin levels in the cecum and large intestine and maintained baseline levels of superoxide dismutase (SOD), suggesting protection of the intestinal mucosa. These findings indicate that CG fractions exhibit microbiota-modulating and protective effects against STEC, highlighting their therapeutic potential and the need for further studies to elucidate the underlying mechanisms.

This study explored the conversion of citrus juice side streams into fermentable oligosaccharides for potential gut health benefits. Alcohol washed, insoluble lemon peel waste was enzymatically treated using technical pectinolytic enzyme preparations, yielding mixtures of galactose- arabinose- and either methyl-esterified or non-methyl-esterified galacturonic acid oligosaccharides (OS) with a Δ4,5-unsaturated non-reducing end resulting in mixtures of pectin-derived OS: POS and POSNME. Both mixtures were completely fermented during in vitro batch fermentation by proximal and distal microbiota of three healthy adult donors. Fermentation by distal and proximal microbiota resulted in similar methyl-ester-dependent mechanisms of POS utilization, yielding health beneficial acetate, propionate and butyrate in significant amounts. Arabinose-, galactose- and non-methyl-esterified Δ4,5-unsaturated galacturonic acid OS were utilized significantly faster by the distal and proximal microbiota of donors 1 and 2 compared to methyl-esterified Δ4,5-unsaturated galacturonic acid OS, suggesting methyl-esterification of Δ4,5-unsaturated galacturonic acid oligosaccharides as a substantial regulator of POS fermentability. The findings presented in this manuscript suggest that carbohydrate molecular structure and availability, rather than microbiota composition, determine carbohydrate fermentation patterns along the colon, emphasizing that the consumption of differently fermentable fiber is essential to promote gut health along the colon.

Microbial genome-wide association studies (GWAS) have uncovered numerous host genetic variants associated with gut microbiota. However, links between host genetics, the gut microbiome and specific cellular contexts remain unclear. Here we use a computational framework, scBPS (single-cell Bacteria Polygenic Score), to integrate existing microbial GWAS and single-cell RNA-sequencing profiles of 24 human organs, including the liver, pancreas, lung and intestine, to identify host tissues and cell types relevant to gut microbes. Analysing 207 microbial taxa and 254 host cell types, scBPS-inferred cellular enrichments confirmed known biology such as dominant communications between gut microbes and the digestive tissue module and liver epithelial cell compartment. scBPS also identified a robust association between Collinsella and the central-veinal hepatocyte subpopulation. We experimentally validated the causal effects of Collinsella on cholesterol metabolism in mice through single-nuclei RNA sequencing on liver tissue to identify relevant cell subpopulations. Mechanistically, oral gavage of Collinsella modulated cholesterol pathway gene expression in central-veinal hepatocytes. We further validated our approach using independent microbial GWAS data, alongside single-cell and bulk transcriptomic analyses, demonstrating its robustness and reproducibility. Together, scBPS enables a systematic mapping of the host-microbe crosstalk by linking cell populations to their interacting gut microbes.

Phage therapy presents a promising solution for combating multidrug-resistant (MDR) bacterial infections and other bacteria-related diseases, attributed to their innate ability to target and lyse bacteria. Recent clinical successes, particularly in treating MDR-related respiratory and post-surgical infections, validated the therapeutic potential of phage therapy. However, the complex microenvironment within the human body poses significant challenges to phage activity and efficacy in vivo. To overcome these barriers, recent advances in phage engineering have aimed to enhance targeting accuracy, improve stability and survivability, and explore synergistic combinations with other therapeutic modalities. This review provides a comprehensive overview of phage therapy, emphasizing the application of engineered phages in antibacterial therapy, tumor therapy, and vaccine development. Furthermore, the review highlights the current challenges and future trends for advancing phage therapy toward broader clinical applications.

Everyday actions such as eating, tooth brushing or applying cosmetics inherently modulate our microbiome. Advances in sequencing technologies now facilitate detailed microbial profiling, driving intentional microbiome-targeted product development. Inspired by an academic-industry workshop held in January 2024, this review explores the oral, skin and gut microbiomes, focussing on the potential long-term implications of perturbations. Key challenges in microbiome safety assessment include confounding factors (ecological variability, host influences and external conditions like geography and diet) and biases from experimental measurements and bioinformatics analyses. The taxonomic composition of the microbiome has been associated with both health and disease, and perturbations like regular disruption of the dental biofilm are essential for preventing caries and inflammatory gum disease. However, further research is required to understand the potential long-term impacts of microbiome disturbances, particularly in vulnerable populations including infants. We propose that emerging technologies, such as omics technologies to characterize microbiome functions rather than taxa, leveraging artificial intelligence to interpret clinical study data and in vitro models to characterize and measure host-microbiome interaction endpoints, could all enhance the risk assessments. The workshop emphasized the importance of detailed documentation, transparency and openness in computational models to reduce uncertainties. Harmonisation of methods could help bridge regulatory gaps and streamline safety assessments but should remain flexible enough to allow innovation and technological advancements. Continued scientific collaboration and public engagement are critical for long-term microbiome monitoring, which is essential to advancing safety assessments of microbiome perturbations.

The rice-duck-crayfish (RDC) coculture system, an ecologically efficient breeding strategy that accommodates natural behavior of ducks and improves their welfare. The optimal stocking density and its impact on duck health in this system remains undetermined. The study examined the impact of stocking densities on growth, organ index, serum biochemistry, gut morphology and microbiota of ducks in RDC system.

A total of five hundred and forty 20-day-old Nonghu No. 2 ducks were randomly allocated based on density: low-density (LD; 8 birds/666.67 m2), mediumdensity (MD; 12 birds/666.67 m2) and high-density (HD; 16 birds/666.67 m2) groups, with three replicates in each group, and the symbiosis period was up to 40 days until rice tasselling.

There were no significant differences in final body weight, average daily gain, or feed:gain ratio between groups (p>0.05); however, the liver and spleen indices of ducks in HD group were significantly greater than those in LD group (p<0.05). The serum albumin concentration in HD group decreased, whereas creatine kinase activity increased (p<0.05). Additionally, the ileal crypt depth significantly increased and the ileal villus height and villus/crypt ratio significantly decreased in ducks in MD and HD groups compared to LD group (p<0.05). Moreover, the abundance of cecal Deferribacterota and Spirochaetota increased significantly (p<0.05), while the abundance of Firmicutes decreased significantly (p<0.05) with increasing stocking density. Moreover, the increase in stocking density significantly decreased the abundance of some beneficial bacteria (Faecalibacterium and Fournierella) and increased the abundance of some harmful bacteria (Mucispirillum and Brachyspira) (p<0.05).

These results suggest that moderately HD breeding doesn't significantly affect duck growth, but increased stocking density led to changes in cecal microbiota and dysbiosis. Reducing stocking density positively affects immune parameters and ileum morphology. However, due to the limited number of total replicates of the study, further research is needed to validate the reliability of the results.

Cancer metastasis is the leading cause of death in patients. In recent years, there has been a growing recognition of the role of tumor-associated microflora in tumor metastasis. The connection between oral and gut microflora and the tumor microenvironment has also been extensively studied. The migration of oral and gut microflora is closely associated with tumor development. Although there is awareness regarding the significant impact of microbial communities on human health, the focus on their relationship with host organisms, particularly those related to tumor-associated microflora, remains inadequate. As an integral part of the body, the host microflora is crucial for regulating the cancer risk and preventing tumor recurrence. The oral-gut axis plays an indispensable role in human immunity, and many types of cancers, such as colorectal, pancreatic, and breast, are significantly influenced by their internal microbial communities. However, further exploration into the mechanisms underlying the role of the intratumoral microflora in cancer is necessary to achieve a comprehensive understanding. We have summarized and analyzed related articles in PubMed. This article reviews the impact of the oral-gut axis on the human immune system, explores the relationship between the translocation of the oral and intestinal flora and the tumor microenvironment, analyzes the specific mechanisms involved in the translocation of the oral and intestinal microflora during the evolution and progression of tumors, and elaborates on the correlations between the occurrence and development of tumors and the changes in the microflora. Finally, a summary of these abovementioned points is provided.

Colorectal cancer (CRC) is a major global health challenge. Emerging research highlights the pivotal role of the gut microbiota in influencing CRC risk, progression, and treatment response. Metagenomic approaches, especially high-throughput shotgun sequencing, have provided unprecedented insights into the intricate connections between the gut microbiome and CRC. By enabling comprehensive taxonomic and functional profiling, metagenomics has revealed microbial signatures, activities, and biomarkers associated with colorectal tumorigenesis. Furthermore, metagenomics has shown a potential to guide patient stratification, predict treatment outcomes, and inform microbiome-targeted interventions. Despite remaining challenges in multi-omics data integration, taxonomic gaps, and validation across diverse cohorts, metagenomics has propelled our comprehension of the intricate gut microbiome-CRC interplay. This review underscores the clinical relevance of microbial signatures as potential diagnostic and prognostic tools in CRC. Furthermore, it discusses personalized treatment strategies guided by this omics' approach.

Laryngeal cancer incidence is rising globally; the role of gut microbiota remains underexplored. This study aimed to establish a causal link between gut microbiota and laryngeal cancer to inform preventive and therapeutic strategies.

Gut microbiota data from GWAS conducted by the MiBioGen consortium served as the exposure variable, with laryngeal cancer as the outcome variable. the exposure variable and the outcome variable were analyzed using Mendelian Randomization. The primary method was Inverse Variance Weighted analysis, with heterogeneity and pleiotropy assessed through Cochran's Q test, MR-Egger regression, and MR-PRESSO.

In the study, we identified five bacterial taxa with potential causal relationships with laryngeal cancer risk: Higher levels of Clostridiaceae1 (OR = 0.9993, 95% CI 0.9986-0.9999, p = 0.0463) and Turicibacter (OR = 0.9995, 95% CI 0.9989-0.9999, p = 0.0384) were linked to reduced cancer risk, while Mollicutes RF9 (OR = 1.0010, 95% CI 1.0003-1.0016, p = 0.0027), Euryarchaeota (OR = 1.0004, 95% CI 1.0001-1.0007, p = 0.0234), and Cyanobacteria (OR = 1.0005, 95% CI 1.0000-1.0009, p = 0.0464) were associated with increased risk.

Our findings suggest a causal relationship between gut microbiota composition and laryngeal cancer risk. Clostridiaceae1 and Turicibacter may play a protective role, while Mollicutes RF9, Euryarchaeota, and Cyanobacteria could contribute to increased cancer susceptibility. These insights highlight potential microbiome-based strategies for early detection, prevention, and therapeutic intervention in laryngeal cancer.

Level 5.

The COVID-19 pandemic has highlighted the need for a comprehensive understanding of the factors influencing disease severity and progression. Emerging research indicates that the human microbiota, particularly beneficial bacteria, significantly impacts immune responses and health outcomes in COVID-19 patients. While existing studies provide general insights into the relationship between the microbiota and probiotics with COVID-19, they often lack a detailed exploration of how specific bacterial taxa might be used as adjunctive treatments. This review aims to address this gap by focusing on ten key genera of beneficial bacteria, discussing their roles in COVID-19 and evaluating their potential as probiotics for prevention and treatment. The review covers the impact of these microbes on human health, their population alterations in COVID-19 patients, and their interactions with other viral infections. Among these microbes, several exhibit distinct patterns of abundance in COVID-19 patients, influencing disease outcomes and highlighting their potential roles in infection dynamics. In COVID-19 patients, populations of Akkermansia, Ruminococcus, and Roseburia are consistently reduced, while those of Faecalibacterium show a significant decline in more severe cases. Bacteroides presents varying effects depending on the species involved. Alterations in the abundance of Blautia and Lachnospiraceae are associated with increased inflammation and disease severity. Likewise, the depletion of Lachnospira and Coprococcus populations, both linked to anti-inflammatory effects, may exacerbate symptom severity. Oscillospira, though less studied, is connected to overall health and could have implications for viral infections. This review synthesizes the current understanding of these beneficial microbes to highlight the importance of maintaining a healthy microbiota to alleviate the impact of COVID-19 and contribute to the development of novel therapeutic strategies involving microbiota modulation.

The human body functions as a complex ecosystem, hosting trillions of microbes that collectively form the microbiome, pivotal in immune system regulation. The host-microbe immunological axis maintains homeostasis and influences key physiological processes, including metabolism, epithelial integrity, and neural function. Recent advancements in microbiome-based therapeutics, including probiotics, prebiotics and fecal microbiota transplantation, offer promising strategies for immune modulation. Microbial therapies leveraging microbial metabolites and engineered bacterial consortia are emerging as novel therapeutic strategies. However, significant challenges remain, including individual microbiome variability, the complexity of host-microbe interactions, and the need for precise mechanistic insights. This review comprehensively examines the host microbiota immunological interactions, elucidating its mechanisms, therapeutic potential, and the future directions of microbiome-based immunomodulation in human health. It will also critically evaluate challenges, limitations, and future directions for microbiome-based precision medicine.

Research has established links between the gut microbiome (GM) and both obesity and type 2 diabetes (T2D), which is much discussed, but underexplored. This study employed body mass index (BMI) as the measurement of obesity to delve deeper into the correlations from a genetic perspective.

We performed the Mendelian randomization (MR) analysis to examine the causal effects of GM on T2D and BMI, and vice versa. Genome-wide association study (GWAS) summary datasets were utilized for the analysis, including T2D (N = 933,970), BMI (N = 806,834), and two GM datasets from the international consortium MiBioGen (211 taxa, N = 18,340) and the Dutch Microbiome Project (DMP) (207 taxa, N = 7,738). These datasets mainly cover European populations, with additional cohorts from Asia and other regions. To further explore the potential mediating role of GM in the connections between BMI and T2D, their interaction patterns were summarized into a network.

MR analysis identified 9 taxa that showed protective properties against T2D. Seven species were within the Firmicutes and Bacteroidales phyla in the DMP, and two were from the MiBioGen (Odds Ratio (OR): 0.94-0.95). Conversely, genetic components contributing to the abundance of 12 taxa were associated with increased risks of T2D (OR: 1.04-1.12). Furthermore, T2D may elevate the abundance of seven taxa (OR: 1.03-1.08) and reduce the abundance of six taxa (OR: 0.93-0.97). In the analysis of the influence of the genetic component of BMI on GM composition, BMI affected 52 bacterial taxa, with 28 decreasing (OR: 0.75-0.92) and 24 increasing (OR: 1.08-1.27). Besides, abundances of 25 taxa were negatively correlated with BMI (OR: 0.95-0.99), while positive correlations were detected for 14 taxa (OR: 1.01-1.05). Notably, we uncovered 11 taxa genetically associated with both BMI and T2D, which formed an interactive network.

Our findings provide evidence for the GM-mediated links between obesity and T2D. The identification of relevant GM taxa offers valuable insights into the potential role of the microbiome in these diseases.

Thousands of biomarkers have been discovered to solve the mechanisms of cancer, but dynamic alterations in the parameters that affect cancer progression cause complex disease status. Therefore, it is essential when dealing with cancer to analyze all parameters, including pathway information, to understand the disease mechanism of action. In our study, we applied multi-omics data integration for microbiome, transcriptome, and microbial pathway datasets obtained from colorectal cancer patients. The Cldn7 gene and Fusobacteria, which both play roles in the stability of the intestinal barrier, were found to be highly associated with each other (r = 0.71). The Klf3 gene has been identified as a critical regulator in the activation of the WNT1 and WNT/β-catenin signaling pathways. Notably, it exhibited a strong positive correlation with the presence of Fusobacteria, which are also implicated in modulating these pathways. In addition, the glutaryl CoA degradation and p-cymene degradation pathways demonstrated a strong positive association with the expression of the Ahcy, Eis2s2, Hsp90ab1, Psma7, Lbr, Rpl7l1, Cse1l, Cbx3, Ncl, Hspd1, Tpx2, and Top2a genes (r > 0.65), suggesting their potential involvement in the regulation and metabolic integration of these pathways at the transcriptional level.

Ziziphi Spinosae Semen saponins (ZSSS) show sedative-hypnotic activity but have very low bioavailability, potentially due to their conversion into bioactive metabolites by gut microbiota. In this study, the biotransformation of ZSSS by gut microbiota from healthy humans and patients with insomnia in vitro was analyzed. A total of 21 prototype compounds and 49 metabolites were identified using UHPLC-Q-Orbitrap-MS. Deglycosylation, deoxygenation, dehydration, and deacylation were detected in both healthy individuals and insomniacs. However, oxidation and hydrogenation were uniquely observed in insomniacs. ZSSS can enhance beneficial bacteria, such as Veillonella, Dialister, and Bacteroides. ZSSS can promote the synthesis of short-chain fatty acids (SCFAs), especially acetic acid, propionic acid, and butyric acid. Furthermore, it was found that the sedative-hypnotic activity of ZSSS was enhanced after biotransformation, as determined by a sodium pentobarbital-induced sleeping test (SPST), open-field behavior test (OFBT), and molecular docking experiment (MDE). These results collectively offer valuable insight into the mechanism of action of ZSSS.

The rumen microbiome plays a critical role in nutrient metabolism and adaptation of the yak (Bos grunniens), an import livestock animal of the Qinghai-Tibet Plateau renowned for their superior plant fiber degradation capacity. However, the microbiome among the different ecological niches within yak's rumen remains unelucidated. Through shotgun sequencing of rumen solid and liquid fractions from five yaks, we identified significant differences in the microbial communities and their genetic functions between the solid and liquid fractions. Solid fractions exhibited dominance by Ruminococcus, Succiniclasticum, and Aspergillus, while Prevotella, Paludibacter, Parabacteroides, and Bacteroides prevailed in liquid fractions. Comparative CAZyme profiling revealed solid fractions were significantly enriched in cellulose/hemicellulose-targeting enzymes (GH5, GH11, and CBM63), implicating their specialization in breaking down the fibrous grasses. In contrast, liquid fractions showed higher abundances of starch-degrading enzymes (GH13, CBM48) and host-glycan utilizers (GH92), suggesting roles in soluble nutrient extraction and host-microbe interactions. Comparative analysis of 574 metagenome-assembled genomes suggested that Methanomethylophilaceae_UBA71 and nitrate-respiring Ruminococcaceae_Firm-04 preferentially colonized in the solids, whereas propionate-producing Quinella and animal glycan-degrading Bacteroides were more prevalent in the liquids. Moreover, compared to Hu sheep, yak's rumen microbiome showed significantly enhanced utilization of plant polysaccharide capacity. Comparative analysis across 10 ruminant species further highlighted host phylogeny as a key driver of rumen microbiome variation. These findings advance our understanding of niche differentiation and functional specialization within the unique yak rumen ecosystem.

Avian pathogenic Escherichia coli (APEC) threatens both poultry production and human health. Xylooligosaccharides (XOS) may suppress pathogenic bacteria through prebiotic actions. However, the influences of single degree of polymerization (DP) on the inhibition of APEC by XOS remain unknown. This study aimed to probe if XOS and their major monomers (xylobiose, xylotriose and xylotetraose) could differentially combat APEC via prebiotic actions using an in vitro fermentation model with chicken cecal microbiota.

Microbiota were randomly divided into 7 groups (5 replicate tubes/group). Control group (CON) received no treatment; XOS group received commercial XOS mixtures; APEC group received APEC; XA, X2, X3 and X4 groups received APEC combined with commercial XOS mixtures, xylobiose, xylotriose and xylotetraose, respectively.

XOS and their major monomers mitigated APEC-induced decline (p < 0.05) in gut microbial α-diversity, with xylotetrose showing the least effect. Gut microbiota in XA, X2, X3 and X4 groups clustered together, with a relative separation observed in X4 group. XOS and their monomers elevated (p < 0.05) the abundances of Firmicutes, Bacteroidota and several probiotics (Lactobacillus, Bacteroides and Megamonas), but reduced (p < 0.05) the abundances of Proteobacteria and Escherichia-Shigella, with xylotetraose exhibiting the least efficacy. Besides, xylotriose and xylotetrose had an advantage over xylotetraose in promoting microbial production of short-chain fatty acids. Metabolomics analysis revealed that APEC challenge mainly downregulated (p < 0.05) several amino acids metabolism pathways of gut microbiota, while xylotriose had an inferiority to XOS in upregulating (p < 0.05) histidine metabolism pathway. Furthermore, microbial fermentation metabolites of all XOS monomers lowered (p < 0.05) certain virulence genes expression in APEC, with xylotriose being the most advantageous.

XOS and their major monomers differentially improved gut microbiota and metabolite profiles in chicken gut against APEC challenge. Overall, xylotriose exhibited the greatest inhibition against APEC abundance and virulence. Our findings underscore the role of single DP in influencing the prebiotic actions of XOS against APEC, providing a basis for the reasonable application of XOS in diets to combat bacterial challenge.

Trillions of microorganisms play a pivotal role in maintaining health and preventing disease in humans. Their presence influences daily life, habits, energy levels, and pathologies. The present narrative review synthesized recent studies of microbial diversity across organ systems. The composition of the microbiota regulates the intestinal barrier, modulates the immune response, influences metabolism, and produces essential compounds such as short-chain fatty acids and neurotransmitters. Dysbiosis is associated with numerous pathologies, including metabolic, autoimmune, neurodegenerative, and cardiovascular diseases. The microbiota is key to maintaining physiological balance and reducing disease risk. Therapeutic interventions, such as probiotics, prebiotics, postbiotics, and microbiome transplantation, offer promising perspectives in restoring microbial homeostasis and preventing chronic diseases.

This study aimed to enhance the in vitro hypoglycemic activity of mulberry twigs polysaccharides (MTP) through ultrasonic degradation and to elucidate its underlying mechanisms and prebiotic potential. The results demonstrated that ultrasonic degradation effectively increased its inhibitory activity against α-glucosidase. Structural characterization of MTP revealed that ultrasonic degradation significantly decreasing its molecular weight and monosaccharide composition. Mechanistic studies indicated that the inhibition of α-glucosidase by the degraded product MTP-240 was reversible and followed a single static quenching process. In vitro fermentation assays revealed that MTP-240 promoted the production of short-chain fatty acids (SCFAs), surpassing the inulin control, with pentanoic acid accumulating most substantially. Additionally, MTP-240 enhanced the growth of Bifidobacterium, a beneficial gut bacterium associated with improved glucose levels and antioxidant capacity. These findings suggested that ultrasonic degradation was an effective method for enhancing the glycosidase inhibitory activity of polysaccharides, and the degraded MTP possesses the potential to be developed as a food additive with dual functions of glycosidase inhibition and prebiotic activity. This research provides a theoretical basis for the further development of mulberry resources and related functional foods.

Gut microbiota plays a critical role in counteracting enteric viral infection. Our previous study demonstrated that infection of porcine deltacoronavirus (PDCoV) disturbs gut microbiota and causes intestinal damage and inflammation in piglets. However, the influence of gut microbiota on PDCoV infection remains unclear.

Firstly, the relationship between gut microbiota and disease severity of PDCoV infection was evaluated using 8-day-old and 90-day-old pigs. The composition of gut microbiota was significantly altered in 8-day-old piglets after PDCoV infection, leading to severe diarrhea and intestinal damage. In contrast, PDCoV infection barely affected the 90-day-old pigs. Moreover, the diversity (richness and evenness) of microbiota in 90-day-old pigs was much higher compared to the 8-day-old piglets, suggesting the gut microbiota is possibly associated with the severity of PDCoV infection. Subsequently, transplanting the fecal microbiota from the 90-day-old pigs to the 3-day-old piglets alleviated clinical signs of PDCoV infection, modulated the diversity and composition of gut microbiota, and maintained the physical and chemical barrier of intestines. Additionally, metabolomic analysis revealed that the fecal microbiota transplantation (FMT) treatment upregulated the swine intestinal arginine biosynthesis, FMT significantly inhibited the inflammatory response in piglet intestine by modulating the TLR4/MyD88/NF-κB signaling pathway.

PDCoV infection altered the structure and composition of the gut microbiota in neonatal pigs. FMT treatment mitigated the clinical signs of PDCoV infection in the piglets by modulating the gut microbiota composition and intestinal barrier, downregulating the inflammatory response. The preventive effect of FMT provides novel targets for the development of therapeutics against enteropathogenic coronaviruses. Video Abstract.

Background: The World Health Organization has indicated that airport noise is strongly associated with cardiovascular disease, with vascular inflammation identified as the primary mechanism. Therefore, long-term exposure to airport noise is considered far more harmful than other types of noise. However, there remains a lack of research into the mechanisms underlying long-term exposure to airport noise and harm to the human body. Methods: A mouse model was established and exposed to airport noise at a maximum sound pressure level of 95 dB(A) and an equivalent continuous sound pressure level of 72 dB(A) for 12 h per day over a period of 100 days. Quantitative polymerase chain reaction (qPCR) was used to detect the mRNA expression levels of pro-inflammatory and anti-inflammatory factors. Enzyme-linked immunosorbent assay (ELISA) was used to detect LPS, LTA, TMA, and TMAO levels. Intestinal flora composition was analyzed by 16S rDNA sequencing, and targeted metabolomics was employed to determine the levels of serum short-chain fatty acids. Results: Long-term airport noise exposure significantly increased systolic blood pressure, diastolic blood pressure, and mean blood pressure (p < 0.05); significantly increased the mRNA expression levels of oxidative stress parameters (nuclear matrix protein 2, 3-nitrotyrosine, and monocyte chemoattractant protein-1) (p < 0.05); significantly increased pro-inflammatory factors (interleukin 6 and tumor necrosis factor alpha) (p < 0.05); significantly decreased the mRNA expression level of anti-inflammatory factor interleukin 10 (p < 0.05); and significantly increased the content of LPS and LTA (p < 0.05). The composition of the main flora in the intestinal tract was structurally disordered, and there were significant differences between the noise-exposed and control groups at the levels of the phylum, family, and genus of bacteria. β-diversity of the principal component analysis diagrams was clearly distinguished. Compared with those of the control group, TMA-producing bacteria and levels of TMA and TMAO were significantly reduced, and the serum ethanoic acid and propanoic acid levels of the noise-exposed group were significantly decreased (p < 0.05). Conclusions: Long-term airport noise exposure causes significant elevation of blood pressure and structural disruption in the composition of the intestinal flora in mice, leading to elevated levels of oxidative stress and inflammation, resulting in metabolic disorders that lead to significant changes in the production of metabolites.