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 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.

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.

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.

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.

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.

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.

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.

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 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.

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.

The reciprocal relationship between aging and alterations in the gut microbiota is a subject of ongoing research. While the role of bacteria in the gut microbiome is well-documented, specific changes in the composition of methanogens during extreme aging and the impact of high methane production in general on health remain unclear. This study was designed to explore the association of predominant methanogenic archaea within the human gut and aging.

Shotgun metagenomic data from the stool samples of young adults (n = 127, Age: 19-59 y), older adults (n = 86, Age: 60-99 y), and centenarians (n = 34, age: 100-109 years) were analyzed.

Our findings reveal a compelling link between age and the prevalence of high methanogen phenotype, while overall archaeal diversity diminishes. Surprisingly, the archaeal composition of methanogens in the microbiome of centenarians appears more akin to that of younger adults, showing an increase in Methanobrevibacter smithii, rather than Candidatus Methanobrevibacter intestini. Remarkably, Ca. M. intestini emerged as a central player in the stability of the archaea-bacteria network in adults, paving the way for M. smithii in older adults and centenarians. Notably, centenarians exhibit a highly complex and stable network of these two methanogens with other bacteria. The mutual exclusion between Lachnospiraceae and these methanogens throughout all age groups suggests that these archaeal communities may compensate for the age-related drop in Lachnospiraceae by co-occurring with Oscillospiraceae.

This study underscores the dynamics of archaeal microbiome in human physiology and aging. It highlights age-related shifts in methanogen composition, emphasizing the significance of both M. smithii and Ca. M. intestini and their partnership with butyrate-producing bacteria for potential enhanced health.

Colorectal cancer (CRC) is a prevalent global malignancy with complex etiologies, including microbiota alterations. This study investigates gut microbiota and biofilm-producing bacteria in 35 Thai CRC patients, analyzing paired normal and tumor biopsy samples. Bacterial DNA from the V3-V4 region of 16S rRNA was sequenced, and biofilms were visualized via scanning electron microscopy and fluorescence in situ hybridization (FISH). Results revealed Firmicutes as the dominant phylum, followed by Bacteroidota, Proteobacteria, and Fusobacteriota, with Fusobacteriota and Bacteroidota notably enriched in left-sided CRC. Key biofilm producers-Bacteroides fragilis, Fusobacterium nucleatum, and Pasteurella stomatis-showed significantly higher gene expression in tumor tissues. Dense biofilms and higher Fusobacterium abundance, localized within the crypts of Lieberkuhn, were observed in CRC tissues. These findings highlight CRC-associated microbiota alterations and pathogenic biofilm production, emphasizing a spatial relationship between tumor location and microbial distribution, with potential implications for understanding CRC pathogenesis and therapeutic targeting.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and behavior, frequently accompanied by restricted and repetitive patterns of interests or activities. The gut microbiota has been implicated in the etiology of ASD due to its impact on the bidirectional communication pathway known as the gut-brain axis. However, the precise involvement of the gut microbiota in the causation of ASD is unclear. This study critically examines recent evidence to rationalize a probable mechanism in which gut microbiota symbiosis can induce neuroinflammation through intermediator cytokines and metabolites. To develop ASD, loss of the integrity of the intestinal barrier, activation of microglia, and dysregulation of neurotransmitters are caused by neural inflammatory factors. It has emphasized the potential role of neuroinflammatory intermediates linked to gut microbiota alterations in individuals with ASD. Specifically, cytokines like brain-derived neurotrophic factor, calprotectin, eotaxin, and some metabolites and microRNAs have been considered etiological biomarkers. We have also overviewed how probiotic trials may be used as a therapeutic strategy in ASD to reestablish a healthy balance in the gut microbiota. Evidence indicates neuroinflammation induced by dysregulated gut microbiota in ASD, yet there is little clarity based on analysis of the circulating immune profile. It deems the repair of microbiota load would lower inflammatory chaos in the GI tract, correct neuroinflammatory mediators, and modulate the neurotransmitters to attenuate autism. The interaction between the gut and the brain, along with alterations in microbiota and neuroinflammatory biomarkers, serves as a foundational background for understanding the etiology, diagnosis, prognosis, and treatment of autism spectrum disorder.

Colorectal cancer (CRC) is a prevalent form of cancer in humans, with the gut microbiota playing a significant role in its pathogenesis. Although previous research has primarily focused on the role of primary metabolites produced by gut microbes in CRC development, the role of secondary metabolites remains largely unexplored. Secondary metabolites are known to mediate crucial interactions between the microbiota and the host, potentially influencing CRC progression. However, their specific relationship to CRC pathogenesis is poorly understood. To address this gap, we performed a meta-analysis using fecal metagenomic data from a cohort of CRC patients and healthy controls, aiming to identify CRC-associated microbial secondary metabolite biosynthetic gene clusters (BGCs). Our findings not only provide valuable insights into the pathogenicity and carcinogenicity of CRC but also shed light on the potential mechanisms underlying its development.

Colorectal cancer (CRC) is one of the most prevalent and lethal cancers worldwide, ranking third in incidence and second in mortality. While immunotherapy has shown promise in patients with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H), its effectiveness in proficient mismatch repair (pMMR) or microsatellite stable (MSS) CRC remains limited. Recent advances highlight the gut microbiota as a potential modulator of anti-tumor immunity. The gut microbiome can significantly influence the efficacy of immune checkpoint inhibitors (ICIs), especially in pMMR/MSS CRC, by modulating immune responses and systemic inflammation. This review explores the role of the gut microbiota in pMMR/MSS CRC, the mechanisms by which it may enhance immunotherapy, and current strategies for microbiota modulation. We discuss the potential benefits of combining microbiota-targeting interventions with immunotherapy to improve treatment outcomes for pMMR/MSS CRC patients.

The genus Fusobacterium contains multiple proteolytic opportunistic pathogens that have been increasingly linked to colorectal cancer (CRC). "Oncomicrobes" such as these fusobacterial species within the gut microbiota may contribute to CRC onset and/or progression. Protein-rich diets may both directly increase CRC risk and enrich for proteolytic oncomicrobes, including Fusobacterium spp. Individual food substrates vary in amino acid content, and released amino acid content that is not absorbed in the small intestine may influence the growth of colonic proteolytic fermenters. Fusobacteria such as Fusobacterium spp. are known to preferentially metabolize certain amino acids. As such, some foods may better support the growth of these species within the colonic environment than others. To explore this, in this study, we created free amino acid pools (FAAPs) to represent proportions of amino acids in major proteins of three common dietary protein sources (soy, beef, and bovine milk). Growth curves were generated for 39 Fusobacterium spp. strains cultured in a dilute medium supplemented with each of the three FAAPs. Thereafter, amino acid use by 31 of the 39 Fusobacterium spp. strains in each FAAP treatment was assessed. FAAP supplementation increased growth metrics of all Fusobacterium spp. strains tested; however, the strains varied greatly in terms of the FAAP(s) generating the greatest increase in growth. Furthermore, the amino acid utilization strategy was highly variable between strains of Fusobacterium spp. Neither growth metrics nor amino acid utilization could be explained by species classification of Fusobacterium spp. strains. This report expands upon the previous knowledge of fusobacterial amino acid metabolism and indicates that proteolytic oncomicrobial activity should be assessed in the context of available protein sources.IMPORTANCEFusobacterium spp. including F. animalis, F. nucleatum, F. vincentii, and F. polymorphum are common oral commensals with emerging importance in diseases across multiple body sites, including CRC. CRC lesions associated with fusobacteria tend to result in poorer prognosis and increased disease recurrence. While Fusobacterium spp. are thought to colonize after tumorigenesis, little is known about the factors that facilitate this colonization. Protein-rich diets yielding readily metabolized free amino acids within the colon may promote the growth of proteolytic fermenters such as fusobacteria. Here, we show that variable concentrations of free amino acids within pools that represent different dietary protein sources differentially influence fusobacterial growth, including CRC-relevant strains of Fusobacterium spp. This work highlights the high degree of variation in fusobacterial amino acid utilization patterns and suggests differing proportions of dietary amino acids that reach the colon could influence fusobacterial growth.

In addition to individual genetics, environmental factors (e.g., dietary changes) may influence host susceptibility to gastrointestinal infection through unknown mechanisms. Herein, we developed a model in which CBA/J mice, a genetically resistant strain that tolerates intestinal colonization by the enteric pathogen Salmonella Typhimurium (S. Tm), rapidly succumb to infection after exposure to a diet rich in L-amino acids (AA). In mice, S. Tm-gastroenteritis is restricted to the large intestine (cecum), limiting their use to understand S. Tm small intestine (ileum) colonization, a feature of human Salmonellosis. Surprisingly, CBA mice fed AA diet developed ileitis with enhanced S. Tm ileal colonization. Using germ-free mice and ileal-fecal slurry transplant, we found diet-mediated S. Tm ileal expansion to be microbiota-dependent. Mechanistically, S. Tm relied on Fructosyl-asparagine utilization to expand in the ileum during infection. We demonstrate how AA diet overrides host genetics by altering the gut microbiota's ability to prevent S. Tm ileal colonization.

The intestinal immune barrier is a developed and complex immune system, and there is a fine synergy between it and the induced immune response. Short-chain fatty acids (SCFAs) are the main metabolites of intestinal microbial fermentation. In the cecum of pigs, SCFAs not only provide energy for the host but also participate in regulating the function of the intestinal immune system. The purpose of this study was to explore the mechanism of SCFAs in the regulation of immune gene expression in porcine cecum. SCFAs content and mRNA expression levels of immune genes in cecum were detected, and Gene Ontology (GO) function annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, Protein-Protein Interaction Networks (PPI) network construction, key gene identification, and correlation analysis were performed. The results showed that the content of SCFAs in the cecum of Dahe black pigs (DHB) was lower than that of Dahe pigs (DH). There were significant differences in mRNA expression of some immune genes between the two groups. GO functional annotation found terms related to cytokine activity and protein heterodimerization activity; the KEGG pathway was enriched in several pathways related to intestinal immunity. The PPI network identified Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-10 (IL-10), Interleukin-17A (IL-17A), and Interleukin-18 (IL-18) as key proteins. The correlation analysis showed that acetic acid and valerate were closely related to the immune response. In this study, the differences in cecal short-chain fatty acids and the immune barrier between Dahe pigs and Dahe black pigs were compared, which provided a theoretical basis for improving the intestinal immunity of pigs.

Diabetes is the third most common chronic disorder worldwide. Diabetic wounds are a severe complication that is costly and often results in non-traumatic lower limb amputation. Recent investigations have demonstrated that the gut microbiota as a "virtual organ" can regulate metabolic diseases like diabetes. Fecal microbiota transplantation (FMT) is an innovative therapeutic approach for promoting wound healing, but its function remains incompletely defined. A diabetes model was established by supplying mice with a high-fat diet and performing an intraperitoneal injection of streptozotocin. Diabetic wounds were then created, followed by bacterial transplantation. The relevant indexes of wound healing were evaluated to verify the promoting effect of FMT on the diabetic wounds. Human skin keratinocytes were also cultured, and cell scratch experiments were conducted to further investigate the underlying mechanism. The FMT regulated the levels of specific bacteria in the diabetic mice and helped restore the balance of intestinal microbes. This transplantation also enhanced wound healing in the diabetic mice by augmenting the closure rate, accelerating re-epithelialization, and boosting collagen deposition in skin wounds. Furthermore, FMT promoted the production of IL-17A, which significantly enhanced the growth and movement of human keratinocytes. Inhibiting molecules related to the IL-17A-mTOR-HIF1α signaling axis were shown to hinder wound re-epithelialization.This study clarifies the function of the IL-17A-mTOR-HIF1α signaling axis in the utilization of FMT in diabetic wound healing, providing a new therapeutic method and target for promoting the healing of diabetic wounds.