Chronic kidney disease (CKD) poses a severe health risk with high morbidity and mortality, profoundly affecting patient quality of life and survival. Despite advancements in research, the pathophysiology of CKD remains incompletely understood. Growing evidence links CKD with shifts in gut microbiota function and composition. Natural compounds, particularly polyphenols, have shown promise in CKD treatment due to their antioxidant and anti-inflammatory properties and their ability to modulate gut microbiota. This review discusses recent progress in uncovering the connections between gut microbiota and CKD, including microbiota changes across different kidney diseases. We also examine metabolite alterations,such as trimethylamine-N-oxide, tryptophan derivatives, branched-chain amino acids, short-chain fatty acids, and bile acids,which contribute to CKD progression. Further, we outline the mechanisms through which polyphenols exert therapeutic effects on CKD, focusing on signaling pathways like nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), mammalian target of rapamycin (mTOR), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), phosphatidylin-ositol-3-kinase (PI3K)/protein kinase B (Akt), and toll like receptors (TLR), as well as their impact on gut microbiota. Lastly, we consider how dietary polyphenols could be harnessed as bioactive drugs to slow CKD progression. Future research should prioritize multi-omics approaches to identify patients who would benefit from polyphenolic interventions, enabling personalized treatment strategies to enhance therapeutic efficacy.

Dietary fiber interventions to modulate the gut microbiota have largely relied on isolated fibers or specific fiber sources. We hypothesized that fibers systematically blended could promote more health-related bacterial groups. Initially, pooled in vitro fecal fermentations were used to design dietary fiber mixtures to support complementary microbial groups related to health. Then, microbial responses were compared for the designed mixtures versus their single fiber components in vitro using fecal samples from a separate cohort of 10 healthy adults. The designed fiber mixtures outperformed individual fibers in supporting bacterial taxa across donors resulting in superior alpha diversity and unexpected higher SCFA production. Moreover, unique shifts in community structure and specific taxa were observed for fiber mixtures that were not observed for single fibers, suggesting a synergistic effect when certain fibers are put together. Fiber mixture responses were remarkably more consistent than individual fibers across donors in promoting several taxa, especially butyrate producers from the Clostridium cluster XIVa. This is the first demonstration of synergistic fiber interactions for superior support of a diverse group of important beneficial microbes consistent across people, and unexpectedly high SCFA production. Overall, harnessing the synergistic potential of designed fiber mixtures represents a promising and more efficacious avenue for future prebiotic development.

The probiotic impact of microbes on host metabolism and health depends on both host genetics and bacterial genomic variation. Faecalibacterium prausnitzii is the predominant human gut commensal emerging as a next-generation probiotic. Although this bacterium exhibits substantial intraspecies diversity, it is unclear whether genetically distinct F. prausnitzii strains might lead to functional differences in the gut microbiome. Here, we isolated and characterized a novel F. prausnitzii strain (UT1) that belongs to the most prevalent but underappreciated phylogenetic clade in the global human population. Genome analysis showed that this butyrate-producing isolate carries multiple putative mobile genetic elements, a clade-specific defense system, and a range of carbohydrate catabolic enzymes. Multiomic approaches were used to profile the impact of UT1 on the gut microbiome and associated metabolic activity of C57BL/6 mice at homeostasis. Both 16S rRNA and metagenomic sequencing demonstrated that oral administration of UT1 resulted in profound microbial compositional changes including a significant enrichment of Lactobacillus, Bifidobacterium, and Turicibacter. Functional profiling of the fecal metagenomes revealed a markedly higher abundance of carbohydrate-active enzymes (CAZymes) in UT1-gavaged mice. Accordingly, UT1-conditioned microbiota possessed the elevated capability of utilizing starch in vitro and exhibited a lower availability of microbiota-accessible carbohydrates in the gut. Further analysis uncovered a functional network wherein UT1 reduced the abundance of mucin-degrading CAZymes and microbes, which correlated with a concomitant reduction of fecal mucin glycans. Collectively, our results reveal a crucial role of UT1 in facilitating the carbohydrate metabolism of the gut microbiome and expand our understanding of the genetic and phenotypic diversity of F. prausnitzii.

Over the past 3 years, there has been a growing interest in clinical research regarding the potential involvement of intestinal flora in thyroid cancer (TC). This review delves into the intricate connection between intestinal flora and TC, focusing on the particular intestinal flora that is directly linked to the disease and identifying which may be able to predict potential microbial markers of TC. In order to shed light on the inflammatory pathways connected to the onset of TC, we investigated the impact of intestinal flora on immune modulation and the connection between chronic inflammation when investigating the role of intestinal flora in the pathogenesis of TC. Furthermore, the potential role of intestinal flora metabolites in the regulation of thyroid function was clarified by exploring the effects of short-chain fatty acids and lipopolysaccharide on thyroid hormone synthesis and metabolism. Based on these findings, we further explore the effects of probiotics, prebiotics, postbiotics, vitamins, and trace elements.

Faecalibacterium prausnitzii is one of the most dominant commensal bacteria in the human gut, and certain anti-inflammatory functions have been attributed to a single microbial anti-inflammatory molecule (MAM). Simultaneously, substantial diversity among F. prausnitzii strains is acknowledged, emphasizing the need for strain-level functional studies aimed at developing innovative probiotics. Here, two distinct F. prausnitzii strains, KBL1026 and KBL1027, were isolated from Korean donors, exhibiting notable differences in the relative abundance of F. prausnitzii. Both strains were identified as the core Faecalibacterium amplicon sequence variant (ASV) within the healthy Korean cohort, and their MAM sequences showed a high similarity of 98.6%. However, when a single strain was introduced to mice with dextran sulfate sodium (DSS)-induced colitis, KBL1027 showed the most significant ameliorative effects, including alleviation of colonic inflammation and restoration of gut microbial dysbiosis. Moreover, the supernatant from KBL1027 elevated the secretion of IL-10 cytokine more than that of KBL1026 in mouse bone marrow-derived macrophage (BMDM) cells, suggesting that the strain-specific, anti-inflammatory efficacy of KBL1027 might involve effector compounds other than MAM. Through analysis of the Faecalibacterium pan-genome and comparative genomics, strain-specific functions related to extracellular polysaccharide biosynthesis were identified in KBL1027, which could contribute to the observed morphological disparities. Collectively, our findings highlight the strain-specific, anti-inflammatory functions of F. prausnitzii, even within the same core ASV, emphasizing the influence of their human origin.

Depression is one of the most disabling mental disorders worldwide and characterized by symptoms including worthlessness, anhedonia, sleep, and appetite disturbances. Recently, studies have suggested that tryptophan (Trp) metabolism plays a key role in depressed mood through serotonin and kynurenine pathway involving enzyme tryptophan 5-monooxygenase (TPH) and indoleamine-2,3-dioxygenase (IDO) respectively. Moreover, during neuroinflammation, IDO is activated by proinflammatory cytokines and affects neurogenesis, cognition, disturbed hypothalamic-pituitary-adrenal (HPA) axis, and gut homeostasis by altering the gut bacteria and its metabolites like Trp derivatives. Furthermore, over the decades, researchers have focused on understanding communication between the human microbiome, especially gut microbiota, and mental health, called gut-brain-axis (GBA), particularly through Trp metabolism. Supplementation of probiotics in depression has gained attention from researchers and clinicians. However, there is limited information about probiotics supplementation on depression involving enzyme IDO and kynurenine pathway metabolites. This review discussed the potential role of probiotics in depression through the tryptophan/kynurenine pathway.

Faecalibacterium is one of the most abundant bacteria of the human gut microbiota of healthy adults and is recognized to have positive effects on health. Here, we precisely and comprehensively analyzed the conjugative mobilome of four complete Faecalibacterium genomes. Despite lacking any plasmid, these bacteria harbor a vast arsenal of 130 elements, including 17 integrative and conjugative elements (ICEs) and 83 integrative and mobilizable elements (IMEs), collectively comprising 14-23% of the genome. Genome comparison of two strains isolated from the same fecal sample (Faecalibacterium and Roseburia strains) revealed almost identical elements indicating that transfer of ICEs and IMEs shape gut microbiome. ICEs and IMEs from Faecalibacterium encode many and diverse predicted functions such as defense and stress response (phages, multidrug, antibiotics, oxidative stress, biliar salts, antimicrobial peptides), nutrient import and metabolisms (Fe3+, carbohydrates) and riboflavin synthesis. This hints at their important role in the survival and adaptation of Faecalibacterium strains to the gut ecosystem. A rapid survey of 29 additional Faecalibacterium genomes uncovered many putative ICEs and IMEs, reinforcing their role in the rapid and massive evolution of Faecalibacterium genomes.

Interindividual variability in drug exposure can significantly influence treatment outcomes and may lead to drug concentration-related side effects during tuberculosis (TB) treatment. Although the gut microbiota is known to affect drug metabolism, its impact on anti-TB drugs has not been thoroughly explored. This study sought to elucidate the relationship between pre-treatment gut microbiota and drug exposure levels among patients with pulmonary TB. Two cohorts were analyzed: a discovery cohort (N = 99) and a validation cohort (N = 32), both comprising patients undergoing anti-TB therapy with rifampicin, isoniazid, pyrazinamide, and ethambutol. The gut microbiota patterns of participants from the discovery cohort and the validation cohort were profiled by 16S rRNA gene sequencing and metagenomics, respectively. Analyses of both cohorts robustly established a positive association between pre-treatment microbial diversity and drug exposure, as well as significant differences in gut microbiota composition across various drug exposure groups. At the species level, Faecalibacterium prausnitzii was positively associated with drug exposure to rifampicin. Moreover, functional analysis revealed that starch and sucrose metabolism and secondary bile acid biosynthesis were more abundant in the high drug exposure group. To identify biomarkers capable of stratifying patients based on their drug exposure levels, 11 taxa, represented by Faecalibacterium, were selected in the discovery cohort (AUC = 0.992) and were confirmed in the validation cohort with high predictive accuracy (AUC = 0.894). This study demonstrated a correlation between microbial dysbiosis and reduced exposure to anti-TB medications. Optimizing treatment by regulating gut microbiota to improve drug exposure levels requires further validation through larger scale multicenter clinical trials.

This study explores the impact of Faecalibacterium longum CM04-06 on inflammatory bowel disease (IBD) by regulating gut microbiota in mice.

We reanalyzed the distribution of the CM04-06 genome in the metagenome of the IBD cohort and observed a significantly higher abundance of CM04-06 in healthy individuals compared to patients with UC or CD. The prophylactic administration of CM04-06 was evaluated for its effects on intestinal microbial diversity and community composition after a two-week trial in mice. The intestinal microbiota was characterized using metagenomic sequencing of fecal samples on the DNBSEQ platform. CM04-06 treatment resulted in a significant reduction in the Disease Activity Index (DAI) and histological scores, as well as a decrease in the levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, in both the colon and serum of DSS-induced mice. Furthermore, supplementation with CM04-06 significantly reduced the levels of pro-inflammatory cytokines in both the colon and serum. Additionally, CM04-06 enhanced the integrity of the intestinal epithelial barrier by increasing the expression of tight junction proteins and mucin. Moreover, we observed greater abundances of Faecalibaculum rodentium, Alistipes onderdonkii, Alistipes shahii, and Bifidobacterium animalis after CM04-06 treatment.

CM04-06 prevents and alleviates intestinal inflammation by modulating the composition of the microbiota community, increasing the abundance of beneficial probiotics, and suppressing pro-inflammatory cytokine levels.

The chicken's gastrointestinal tract is home to complex and diverse microbial communities that can be manipulated to enhance health and productivity. Although polyphenols have recently attracted the attention of researchers due to their potent antioxidant capabilities, their impact on the gut microbiota remains largely unexplored. Hence, in this study, we conducted a comprehensive analysis of the effects of dietary supplementation with polyphenol-rich extract from shredded, steam-exploded pine particles (PSPP) on growth, meat quality, and gut microbial dynamics in broiler chickens. Supplementation of PSPP was found to significantly improve birds' FCR until the third week of the trial but only marginally affected meat quality. Based on metataxonomic analyses of the cecal microbiotas of broilers fed increasing concentrations of PSPP, dietary PSPP modulated the composition of the cecal microbiota of the birds with a concomitant increase of Bacteroidetes and a decrease in the Firmicutes population. Similar trends were observed for the proportions of Alistipes and Faecalibacterium at the genus level. Additionally, 43 unique bacterial species were detected in the cecal microbiome of birds fed with PSPP. However, microbial diversity did not vary significantly among treatment groups. A particularly interesting finding was the specialization observed in the microbiome of birds receiving PSPP supplementation. Microbial co-occurrence network analyses revealed substantial modifications in their network structure when compared to control birds. Families like Rikenellaceae and Eubacteriaceae were notably absent, and the number of microbial interactions was drastically lower in the PSPP-fed group. Microbial taxa modeling revealed that the impact of increasing dietary PSPP levels primarily affected genus-level taxa, showing a decreasing trend. Overall, this offers compelling evidence that continuous PSPP supplementation may not only alter the composition of intestinal microbes but also have a profound effect on the interactions among different microbial species. Conversely, PSPP had minimal effects on broilers' performance and meat quality.

Gut microbiota is essential for the function of peripherally-induced regulatory T (pTreg) cells. However, how commensal bacteria affect thymically derived fat-resident Treg cells that harbor a unique expression of peroxisome proliferator-activated receptor (PPAR)-γ and suppress inflammation in visceral adipose tissue (VAT), is not well defined. Here it is revealed that microbiota depletion causes a drastic decline in Treg cell population in VAT, particularly those expressing ST2 (ST2+ Treg), which are largely restored after gut microbiome reconstruction. Mechanistically, gut microbiota-derived butyrate increases VAT ST2+ Treg cells through binding PPARγ. Butyrate supplementation and high fiber diet increase VAT ST2+ Treg population in obese mice, and ameliorated glucose tolerance and visceral inflammation. Furthermore, human omental adipose Treg cells show positive correlation with fecal butyrate and certain butyrate-producing microbes. This study identifies the critical role of gut microbiota-butyrate-PPARγ axis in maintaining VAT Treg population, pinpointing a potential approach to augment VAT Treg population and ameliorate inflammation.

Alternative feed additives are being investigated due to the restriction of antibiotics use to decrease antimicrobial resistance (AMR) in food-producing animals. This study investigated the effects of dietary American cranberry (Vaccinium macrocarpon) and wild blueberry (V. angustifolium) pomaces on the cecal microbiota and resistome profiles as well as the short-chain fatty acid levels. Male broiler chickens Cobb500 were fed a basal diet with either 55 ppm bacitracin methylene disalicylate (BMD); 0.5% (CRP0.5) and 1% (CRP1) cranberry pomace; and 0.5% (LBP0.5) and 1% (LBP1) lowbush blueberry pomace with or without a multienzyme mixture (ENZ). The results showed that at 21 days of age, the total coliform counts decreased in the CRP0.5-fed birds compared to BMD (p < 0.05). The use of pomace significantly increased the abundance of Lactobacillus and Bacteroides regardless of ENZ, while CRP decreased the Proteobacteria phylum abundance. In-feed ENZ tended to increase the relative abundance of genes conferring aminoglycoside resistance. Treatment with CRP0.5 decreased the abundance of cepA genes encoding for macrolide (MACROLIDE) and lincomycin (InuD) resistance while increasing those for tetracycline (tetO and tetX) resistance. These results showed, for the first time, the potential of the studied enzymes in influencing berry pomace's effects on antimicrobial resistance gene profiles in broilers.

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.

The study observed interactions between gut microbiota and male reproductive health, noting that the causal relationships were previously unclear. It aimed to explore the potential cause-and-effect relationship between gut bacteria and male reproductive problems such as inflammation, infertility, and sperm functionality, using a two-sample Mendelian randomization method to examine these connections. The analysis found that certain bacterial genera, such as Erysipelatoclostridium (0.71 [0.55-0.92]), Parasutterella (0.74 [0.57-0.96]), Ruminococcaceae UCG-009 (0.77 [0.60-0.98]), and Slackia (0.69 [0.49-0.96]), showed protective effects against prostatitis. In contrast, other genera like Faecalibacterium (1.59 [1.08-2.34]), Lachnospiraceae UCG004 (1.64 [1.15-2.34]), Odoribacter (1.68 [1.01-2.81]), Paraprevotella (1.28 [1.03-1.60]), and Sutterella (1.58 [1.13-2.19]) were detrimental. Additionally, causal relationships were identified between 2 genera and orchitis and epididymitis, 3 genera and male infertility, and 5 genera and abnormal spermatozoa. Further analysis of sperm-related proteins revealed causal associations between specific bacterial genera and proteins such as SPACA3, SPACA7, SPAG11A, SPAG11B, SPATA9, SPATA20, and ZPBP4. The results remained robust after sensitivity analysis and reverse Mendelian randomization analysis. The study concluded that specific bacterial genera have causal roles in reproductive inflammation, infertility, and sperm-associated proteins. This provides a novel strategy for the early diagnosis and identification of therapeutic targets in reproductive inflammation and infertility.

Supplementation with Bifidobacterium bifidum G9-1 (BBG9-1) has been established to enhance the production of butyrate, a short-chain fatty acid (SCFA) known for its beneficial effects in alleviating constipation. We hypothesized that BBG9-1 alters gut microbiota such that bacteria that produce butyric acid from lactate and acetate become more abundant. In this study, we sought to determine whether BBG9-1 promotes the growth of butyrate-producing bacteria and thereby enhances butyrate production. BBG9-1 was cocultured with different butyrate-producing bacteria to compare differences in the SCFA production of cocultures and monocultures. We indeed detected significant increases in the production of SCFAs in cocultures compared to monocultures. Moreover, lactate and butyrate production increased in a time-dependent manner in the BBG9-1 and Faecalibacterium prausnitzii ID 6052 coculture. In addition, acetate production in cocultures initially increased until 16 h, followed by a decline between 20 and 24 h, and a subsequent significant increase at 48 h. Comparatively, lactate and acetate production in the BBG9-1 and Anaerostipes caccae JCM 13470T coculture peaked at 16 h and declined thereafter, and butyrate production increased in a time-dependent manner. In contrast, lactate, acetate, and butyrate production in the BBG9-1 and Roseburia hominis JCM 17582T coculture increased in a time-dependent manner. These findings indicate that butyrate-producing bacteria increase butyrate production by utilizing BBG9-1-produced lactate and acetate. Thus, the butyrate-mediated physiological activity of BBG9-1 could be attributed to an indirect enhancement of butyrate production.

Background/Objectives: Exposure to high altitudes often results in gastrointestinal disorders. This study aimed to identify probiotic strains that can alleviate such disorders. Methods: We conducted a microbiome analysis to investigate the differences in gut microbiota among volunteers during the acute response and acclimatization phases at high altitudes. Subsequently, we established a mouse model of intestinal barrier damage induced by high-altitude exposure to further investigate the roles of probiotic strains and 2-ketoglutaric acid. Additionally, we performed untargeted metabolomics and transcriptomic analyses to elucidate the underlying mechanisms. Results: The microbiome analysis revealed a significant increase in the abundance of Faecalibacterium prausnitzii during the acclimatization phase. Faecalibacterium duncaniae (F. duncaniae) significantly mitigated damage to the intestinal barrier and the reduction of 2-ketoglutaric acid levels in the cecal contents induced by high-altitude exposure in mice. Immunohistochemistry and TUNEL staining demonstrated that high-altitude exposure significantly decreased the expression of ZO-1 and occludin while increasing apoptosis in ileal tissues. In contrast, treatment with F. duncaniae alleviated the loss of ZO-1 and occludin, as well as the apoptosis induced by high-altitude exposure. Furthermore, 2-ketoglutaric acid also mitigated this damage, reducing the loss of occludin and apoptosis in mice. Transcriptomic analysis indicated that high-altitude exposure significantly affects the calcium signaling pathway; conversely, the administration of F. duncaniae significantly influenced the PPAR signaling pathway, mineral absorption, and the regulation of lipolysis in adipocytes. Additionally, the expression of the FBJ osteosarcoma oncogene (Fos) was markedly reduced following the administration of F. duncaniae. Conclusions:F. duncaniae mitigates hypoxia-induced intestinal barrier damage by increasing levels of 2-ketoglutaric acid and shows promise as a probiotic, ultimately aiding travelers in adapting to high-altitude environments.

Estrogen receptors (ERs) play a critical role in breast cancer (BC) development and progression, with ERα being oncogenic and ERβ exhibiting tumor-suppressive properties. The interaction between ER signaling and other molecular pathways, such as PI3K/AKT/mTOR, influences tumor growth and endocrine resistance. Emerging research highlights the role of prebiotics in modulating gut microbiota, which may influence estrogen metabolism, immune function, and therapeutic responses in BC. This review explores the impact of prebiotics on estrogen receptor modulation, gut microbiota composition, immune regulation, and metabolic pathways in breast cancer. The potential of prebiotics as adjunctive therapies to enhance treatment efficacy and mitigate chemotherapy-related side effects is discussed. A comprehensive analysis of recent preclinical and clinical studies was conducted, examining the role of prebiotics in gut microbiota modulation, immune regulation, and metabolic reprogramming in breast cancer. The impact of short-chain fatty acids (SCFAs) derived from prebiotic fermentation on epigenetic regulation and endocrine resistance was also evaluated. Prebiotics were found to modulate the gut microbiota-estrogen axis, reduce inflammation, and influence immune responses. SCFAs demonstrated selective estrogen receptor downregulation and metabolic reprogramming, suppressing tumor growth. Synbiotic interventions mitigate chemotherapy-related side effects, improving the quality of life in breast cancer patients. Prebiotics offer a promising avenue for breast cancer prevention and therapy by modulating estrogen metabolism, immune function, and metabolic pathways. Future clinical trials are needed to validate their efficacy as adjunctive treatments in breast cancer management.

Members of Eubacteriaceae are involved in host health and diseases. Two Gram-stain-positive, strictly anaerobic, non-motile, non-spore-forming, and rod-shaped bacterial strains, HA2171T and HA2172T, were isolated from the feces of Chinese healthy donors. Based on 16S rRNA gene sequences, HA2171T and HA2172T belonged to the family Eubacteriaceae. Physiological and biochemical characterizations indicated that HA2171T and HA2172T were neutrophilic, mesophilic, and tolerant to low-concentration NaCl. The major cellular fatty acids (>10.0%) of HA2171T were C16:0, C14:0, C18:1ω7c, and C17:0 2-OH, and those of HA2172T were C14:0 and C16:0. MK-6 was the respiratory quinone in both strains. Phylogenetic and phylogenomic analyses showed that HA2171T was closest to Anaerofustis stercorihominis ATCC BAA-858T and that HA2172T as closest to Pseudoramibacter alactolyticus ATCC 23263T. Genome annotation revealed that the HA2171T and HA2172T were able to metabolize carbohydrates and produce acetate and butyrate. HA2172T contains genes associated with hydrogen sulfide production, which is a potential risk for diseases. Based on the phylogenetic, phenotypic, and chemotaxonomic characteristics, we propose that HA2171T and HA2172T represent two novel species, and the names Anaerofustis butyriciformans sp. nov. and Pseudoramibacter faecis sp. nov. are proposed.

Short-chain fatty acids (SCFAs), mainly produced by gut microbiota through the fermentation process of dietary fibers and proteins, are crucial to human health, with butyrate, a famous four-carbon SCFA, standing out for its inevitably regulatory impact on both gut and immune functions. Within this narrative review, the vital physiological functions of SCFAs were examined, with emphasis on butyrate's role as an energy source for colonocytes and its ability to enhance the gut barrier while exhibiting anti-inflammatory effects. Knowledge of butyrate synthesis, primarily generated by Firmicutes bacteria, can be influenced by diets with specifically high contents of resistant starches and fiber. Butyrate can inhibit histone deacetylase, modulate gene expression, influence immune functionality, and regulate tight junction integrity, supporting the idea of its role in gut barrier preservation. Butyrate possesses systemic anti-inflammatory properties, particularly, its capacity to reduce pro-inflammatory cytokines and maintain immune homeostasis, highlighting its therapeutic potential in managing dysbiosis and inflammatory diseases. Although butyrate absorption into circulation is typically minimal, its broader health implications are substantial, especially regarding obesity and type 2 diabetes through its influence on metabolic regulation and inflammation. Furthermore, this narrative review thoroughly examines butyrate's growing recognition as a modulator of neurological health via its interaction with the gut-brain axis. Additionally, butyrate's neuroprotective effects are mediated through activation of specific G-protein-coupled receptors, such as FFAR3 and GPR109a, and inhibition of histone deacetylases (HDACs). Research indicates that butyrate can alleviate neurological disorders, including Alzheimer's, Parkinson's, autism spectrum disorder, and Huntington's disease, by reducing neuroinflammation, enhancing neurotransmitter modulation, and improving histone acetylation. This focus will help unlock its full therapeutic potential for metabolic and neurological health, rather than exclusively on its well-known benefits for gut health, as these are often interconnected.

GLP-1 analogues are a relatively new class of medications that form the cornerstone of diabetes treatment. They possess invaluable glucose-lowering properties without hypoglycemic effects as well as strong cardioprotective effects. The gut microbiome has become the focus of numerous studies, demonstrating its influence not only on the gut but also on the overall well-being of the entire body. However, the effects of GLP-1 analogs on gut microbiota remain uncertain.

Our systematic review (based on PRISMA guidelines) aimed to gather knowledge on the effects of GLP-1 analogue medications on the composition, richness, and abundance of gut microbiota in both animal and human models.

Thirty-eight studies were included in this systematic review. GLP-1 analogues have demonstrated a notable impact on the composition, richness, and diversity of gut microbiota. We can conclude, following the obtained research results of our study, that liraglutide promotes the growth of beneficial genera relevant for beneficial metabolic functions. Exenatide and exendin-4 administration showed various effects on the microbiome composition in animal and human studies. In animal models, it increased genera associated with improved metabolism; however, in human models, genera linked to better metabolic functions and escalated inflammation increased. Following dulaglutide administration, increases in Bacteroides, Akkermansia, and Ruminococcus, genera connected to an improved metabolic model, were significant. Finally, varied results were obtained after semaglutide treatment, in which A. muciniphila, known for its positive metabolic functions, increased; however, microbial diversity decreased. Semaglutide treatment provided various results indicating many confounding factors in semaglutide's impact on the gut microbiota. Results varied due to dissimilarities in the studied populations and the duration of the studies. Further research is essential to confirm these findings and to better recognize their implications for the clinical outcomes of patients.

The gut-brain axis (GBA) represents a sophisticated bidirectional communication system connecting the central nervous system (CNS) and the gastrointestinal (GI) tract. This interplay occurs primarily through neuronal, immune, and metabolic pathways. Dysbiosis in gut microbiota has been associated with multiple neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). In recent years, fecal microbiota transplantation (FMT) has gained attention as an innovative therapeutic approach, aiming to restore microbial balance in the gut while influencing neuroinflammatory and neurodegenerative pathways. This review explores the mechanisms by which FMT impacts the gut-brain axis. Key areas of focus include its ability to reduce neuroinflammation, strengthen gut barrier integrity, regulate neurotransmitter production, and reinstate microbial diversity. Both preclinical and clinical studies indicate that FMT can alleviate motor and cognitive deficits in PD and AD, lower neuroinflammatory markers in MS, and enhance respiratory and neuromuscular functions in ALS. Despite these findings, several challenges remain, including donor selection complexities, uncertainties about long-term safety, and inconsistencies in clinical outcomes. Innovations such as synthetic microbial communities, engineered probiotics, and AI-driven analysis of the microbiome hold the potential to improve the precision and effectiveness of FMT in managing neurodegenerative conditions. Although FMT presents considerable promise as a therapeutic development, its widespread application for neurodegenerative diseases requires thorough validation through well-designed, large-scale clinical trials. It is essential to establish standardized protocols, refine donor selection processes, and deepen our understanding of the molecular mechanisms behind its efficacy.

Non-absorbed dietary emulsifiers, including carboxymethylcellulose (CMC), directly disturb intestinal microbiota, thereby promoting chronic intestinal inflammation in mice. A randomised controlled-feeding study (Functional Research on Emulsifiers in Humans, FRESH) found that CMC also detrimentally impacts intestinal microbiota in some, but not all, healthy individuals.

This study aimed to establish an approach for predicting an individual's sensitivity to dietary emulsifiers via their baseline microbiota.

We evaluated the ability of an in vitro microbiota model (MiniBioReactor Arrray, MBRA) to reproduce and predict an individual donor's sensitivity to emulsifiers. Metagenomes were analysed to identify signatures of emulsifier sensitivity.

Exposure of human microbiotas, maintained in the MBRA, to CMC recapitulated the differential CMC sensitivity previously observed in FRESH subjects. Furthermore, select FRESH control subjects (ie, not fed CMC) had microbiotas that were highly perturbed by CMC exposure in the MBRA model. CMC-induced microbiota perturbability was associated with a baseline metagenomic signature, suggesting the possibility of using one's metagenome to predict sensitivity to dietary emulsifiers. Transplant of human microbiotas that the MBRA model deemed CMC-sensitive, but not those deemed insensitive, into IL-10-/- germfree mice resulted in overt colitis following CMC feeding.

These results suggest that an individual's sensitivity to emulsifier is a consequence of, and can thus be predicted by, examining their baseline microbiota, paving the way to microbiota-based personalised nutrition.

The microbiota-gut-brain axis has been proposed as a potential modulator of mood disorders such as major depression. Complex bidirectional biochemical activities in this axis have been posited to participate in adverse mood disorders. Environmental and genetic factors have dominated recent discussions on depression. The prescription of antibiotics, antidepressants, adverse negative DNA methylation reactions and a dysbiotic gut microbiome have been cited as causal for the development and progression of depression. While research continues to investigate the microbiome-gut-brain axis, this review will explore the state of persistence of gut bacteria that underpins bacterial dormancy, possibly due to adverse environmental conditions and/or pharmaceutical prescriptions. Bacterial dormancy persistence in the intestinal microbial cohort could affect the role of bacterial epigenomes and DNA methylations. DNA methylations are highly motif driven exerting significant control on bacterial phenotypes that can disrupt bacterial metabolism and neurotransmitter formation in the gut, outcomes that can support adverse mood dispositions.

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders primarily comprising two main conditions: ulcerative colitis and Crohn's disease. The gut microbiota's role in driving inflammation in IBD has garnered significant attention, yet the precise mechanisms through which the microbiota influences IBD pathogenesis remain largely unclear. Given the limited therapeutic options for IBD, alternative microbiota-targeted therapies-including prebiotics, probiotics, postbiotics, and symbiotics-have been proposed. While these approaches have shown promising results, microbiota modulation is still mainly considered an adjunct therapy to conventional treatments, with a demonstrated impact on patients' quality of life. Fecal microbiota transplantation (FMT), already approved for treating Clostridioides difficile infection, represents the first in a series of innovative microbiota-based therapies under investigation. Microbial biotherapeutics are emerging as personalized and cutting-edge tools for IBD management, encompassing next-generation probiotics, bacterial consortia, bacteriophages, engineered probiotics, direct metabolic pathway modulation, and nanotherapeutics. This review explores microbial modulation as a therapeutic strategy for IBDs, highlighting current approaches and examining promising tools under development to better understand their potential clinical applications in managing intestinal inflammatory disorders.

Antimicrobial resistance (AMR) is a major public health concern worldwide. International travel is a risk factor for acquiring antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs). Therefore, understanding the transmission of ARB and ARGs is instrumental in tackling AMR. This longitudinal study aimed to assess the benefit of wastewater monitoring in Guadeloupe to evaluate the role of tourism in the spread of AMR.

A wastewater-based surveillance (WBS) study was conducted to monitor AMR in Guadeloupe in 2022 during dry and wet seasons. We characterized the resistome, microbiome and exposome of water samples collected in wastewater treatment facilities of two cities with different levels of tourism activities, in the content of aircraft toilets, and the pumping station receiving effluents from hotels.

The results show that the WBS approach facilitates the differentiation of various untreated effluents concerning exposome, microbiome, and resistome, offering insights into AMR dissemination. Additionally, the findings reveal that microbiome and exposome are comparable across sites and seasons, while resistome characterisation at specific locations may be pertinent for health surveillance. The microbiome of aircraft was predominantly composed of anaerobic bacteria from human intestinal microbiota, whereas the other locations exhibited a blend of human and environmental bacteria. Notably, individuals arriving by air have not introduced clinically significant resistance genes. Exposome compounds have been shown to influence the resistome's variance.

Clear differences were seen between the aircraft and the local sampling sites, indicating that the contribution of tourism to the observed resistance in Guadeloupe is not significant.

Natural killer/T-cell lymphoma (NKTCL) is a highly aggressive malignancy with a dismal prognosis, and gaps remain in understanding the determinants influencing disease outcomes.

To characterise the gut microbiota feature and identify potential probiotics that could ameliorate the development of NKTCL.

This cross-sectional study employed shotgun metagenomic sequencing to profile the gut microbiota in two Chinese NKTCL cohorts, with validation conducted in an independent Korean cohort. Univariable and multivariable Cox proportional hazards analyses were applied to assess associations between identified marker species and patient outcomes. Tumour-suppressing effects were investigated using comprehensive in vivo and in vitro models. In addition, metabolomics, RNA sequencing, chromatin immunoprecipitation sequencing, Western blot analysis, immunohistochemistry and lentiviral-mediated gene knockdown system were used to elucidate the underlying mechanisms.

We first unveiled significant gut microbiota dysbiosis in NKTCL patients, prominently marked by a notable reduction in Faecalibacterium prausnitzii which correlated strongly with shorter survival among patients. Subsequently, we substantiated the antitumour properties of F. prausnitzii in NKTCL mouse models. Furthermore, F. prausnitzii culture supernatant demonstrated significant efficacy in inhibiting NKTCL cell growth. Metabolomics analysis revealed butyrate as a critical metabolite underlying these tumour-suppressing effects, validated in three human NKTCL cell lines and multiple tumour-bearing mouse models. Mechanistically, butyrate suppressed the activation of Janus kinase-signal transducer and activator of transcription pathway through enhancing histone acetylation, promoting the expression of suppressor of cytokine signalling 1.

These findings uncover a distinctive gut microbiota profile in NKTCL and provide a novel perspective on leveraging the therapeutic potential of F. prausnitzii to ameliorate this malignancy.

Changes in the composition of the gut microbiota have been associated with the development of irritable bowel syndrome (IBS). However, to what extent specific bacterial species relate to clinical symptoms remains poorly characterized. We investigated the clinical relevance of bacterial species linked with increased proteolytic activity, histamine production, and superantigen (SAg) production in patients with IBS.

Fecal (n = 309) and nasal (n = 214) samples were collected from patients with IBS and healthy volunteers (HV). Clinical symptoms and gut transit time were evaluated. Bacterial abundance in feces and nasal swabs as well as fecal trypsin-like activity were assessed.

The percentage of fecal samples containing Staphylococcus aureus was significantly higher in IBS compared with HV. Forty-nine percent of S. aureus -positive fecal samples from patients with IBS were also positive for SAgs, compared with 12% of HV. Patients with IBS and positive fecal SAg-producing S. aureus reported higher pain scores than those without S. aureus . Moreover, increased fecal proteolytic activity was associated with abdominal pain. Fecal abundance of Paraprevotella clara and Alistipes putredinis was significantly decreased in IBS, particularly in samples with higher proteolytic activity. Patients with lower Alistipes putredinis or Faecalibacterium prausnitzii abundance reported more severe abdominal pain.

In keeping with our preclinical findings, we show that increased presence of SAg-producing S. aureus in fecal samples of patients with IBS is associated with increased levels of abdominal pain. We also show that increased fecal proteolytic activity is associated with increased abdominal pain in patients with IBS.

Antioxidants, including vitamin E (VE) and grape seed extract (GSE), as anti-aging supplementation have been widely used to improve human health. The gut microbiota plays a crucial role in health and affects the treatment effect of various interventions. However, the role of gut microbiota in VE remains unclear. This study aimed to assess the longitudinal impact of VE treatment on body health and the gut microbiota.

A randomized controlled trial was conducted with 90 healthy individuals. The participants were randomly assigned to three groups: a treatment group receiving VE, another antioxidant treatment group receiving GSE, and a control group receiving a placebo. We found that VE ameliorated blood cholesterol levels by reducing the levels of low-density lipoprotein cholesterol (LDL-C) in healthy volunteers. After the intervention, there was an increase in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria and bile acid metabolizers. Specifically, the abundances of Lachnospira sp. and Faecalibacterium spp. increased in the VE. Interestingly, the gut microbiota of poor responders harbored a greater proportion of disease-associated bacterial species.

VE could promote health by lowering LDL-C, partly and indirectly by affecting gut bacteria with the ability to produce SCFAs or metabolize bile acids.

The clinical trial was registered on August 28, 2021. Registration number was ChiCTR2100050567 (https://www.chictr.org.cn).

Gut microbial dysbiosis and leaky gut play a role in systemic lupus erythematosus (SLE). Geographical location and dietary habits affect the microbiome composition in diverse populations. This study explored the gut microbiome dysbiosis, leaky gut, and systemic immune response to gut bacterial consortium in patients with SLE exhibiting mild/moderate and severe disease activity.

Fecal and blood samples were collected from patients with SLE and healthy volunteers. Genomic DNA was extracted from the stool samples and subjected to 16S rRNA amplicon sequencing and microbiome profiling. Additionally, enzyme-linked immunosorbent assays were employed to determine the serum lipopolysaccharide level, as an assessment of gut permeability, and the systemic immune response against gut bacteria.

Patients with SLE showed significantly lower gut bacterial richness and diversity, indicated by observed OTUs (56.6 vs. 74.44; p = 0.0289), Shannon (3.05 vs. 3.45; p = 0.017) and Simpson indices (0.91 vs. 0.94; p = 0.033). A lower Firmicutes-to-Bacteroidetes ratio (1.07 vs. 1.69; p = 0.01) was observed, with reduced genera such as Ruminococcus 2 (0.003 vs. 0.026; p = 0.0009) and Agathobacter (0.003 vs. 0.012; p < 0.0001) and elevated Escherichia-Shigella (0.04 vs. 0.006; p < 0.0001) and Bacteroides (0.206 vs. 0.094; p = 0.033). Disease severity was associated with a higher relative abundance of Prevotella (0.001 vs. 0.0001; p = 0.04). Medication effects included lower Romboutsia (0.0009 vs. 0.011; p = 0.005) with azathioprine and higher Prevotella (0.003 vs. 0.0002; p = 0.038) with cyclophosphamide. Furthermore, categorization by prednisolone dosage revealed significantly higher relative abundances of Slackia (0.0007 vs. 0.00002; p = 0.0088), Romboutsia (0.009 vs. 0.002; p = 0.0366), and Comamonas (0.002 vs. 0.00007; p = 0.0249) in patients receiving high-dose prednisolone (> 10 mg/day). No differences in serum lipopolysaccharide levels were found, but SLE patients exhibited elevated serum gut bacterial antibody levels, suggesting a systemic immune response.

This study confirms the gut microbiome dysbiosis in patients with SLE, influenced by disease severity and specific medication usage.

The microbiota-gut-brain axis (MGBA) plays a significant role in the maintenance of brain structure and function. The MGBA serves as a conduit between the CNS and the ENS, facilitating communication between the emotional and cognitive centers of the brain via diverse pathways. In the initial stages of this review, we will examine the way how MGBA affects neurogenesis, neuronal dendritic morphology, axonal myelination, microglia structure, brain blood barrier (BBB) structure and permeability, and synaptic structure. Furthermore, we will review the potential mechanistic pathways of neuroplasticity through MGBA influence. The short-chain fatty acids (SCFAs) play a pivotal role in the MGBA, where they can modify the BBB. We will therefore discuss how SCFAs can influence microglia, neuronal, and astrocyte function, as well as their role in brain disorders such as Alzheimer's disease (AD), and Parkinson's disease (PD). Subsequently, we will examine the technical strategies employed to study MGBA interactions, including using germ-free (GF) animals, probiotics, fecal microbiota transplantation (FMT), and antibiotics-induced dysbiosis. Finally, we will examine how particular bacterial strains can affect brain structure and function. By gaining a deeper understanding of the MGBA, it may be possible to facilitate research into microbial-based pharmacological interventions and therapeutic strategies for neurological diseases.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent joint inflammation, damage, and loss of function. In recent years, the role of gut microbiota and its metabolites in immune regulation has attracted increasing attention. The gut microbiota influences the host immune system's homeostasis through various mechanisms, regulating the differentiation, function, and immune tolerance of immune cells. Dysbiosis of the gut microbiota in RA patients is closely associated with abnormal activation of immune cells and excessive secretion of inflammatory cytokines. Metabolites produced by the gut microbiota, such as short-chain fatty acids (SCFAs), tryptophan metabolites, bile acids, and amino acid metabolites, play a critical role in immune responses, regulating the functions of immune cells like T cells, B cells, and macrophages, and inhibiting the release of pro-inflammatory cytokines. Restoring the balance of the gut microbiota and optimizing the production of metabolic products may become a new strategy for RA treatment. This review discusses the role of gut microbiota and its metabolites in the immune response of RA, exploring how they influence the immunopathological process of RA through the regulation of immune cells and key immune factors. It also provides a theoretical basis for future therapeutic strategies based on gut microbiota modulation.

Metagenomics has revealed the incredible diversity of phages within the human gut. However, very few of these phages have been subjected to in-depth experimental characterization. One promising method of obtaining novel phages for experimental characterization is through induction of the prophages integrated into the genomes of cultured gut bacteria. Here, we developed a bioinformatic approach to prophage identification that builds on prophage genomic properties, existing prophage-detecting software, and publicly available virome sequencing data. We applied our approach to 22 strains of bacteria belonging to the genus Faecalibacterium, resulting in identification of 15 candidate prophages, and validated the approach by demonstrating the activity of five prophages from four of the strains. The genomes of three active phages were identical or similar to those of known phages, while the other two active phages were not represented in the Viral RefSeq database. Four of the active phages possessed a diversity-generating retroelement (DGR), and one retroelement had two variable regions. DGRs of two phages were active at the time of the induction experiments, as evidenced by nucleotide variation in sequencing reads. We also predicted that the host range of two active phages may include multiple bacterial species. Finally, we noted that four phages were less prevalent in the metagenomes of inflammatory bowel disease patients compared to a general population cohort, a difference mainly explained by differences in the abundance of the host bacteria. Our study highlights the utility of prophage identification and induction for unraveling phage molecular mechanisms and ecological interactions.IMPORTANCEWhile hundreds of thousands of phage genomes have been discovered in metagenomics studies, only a few of these phages have been characterized experimentally. Here, we explore phage characterization through bioinformatic identification of prophages in genomes of cultured bacteria, followed by prophage induction. Using this approach, we detect the activity of five prophages in four strains of commensal gut bacteria Faecalibacterium. We further note that four of the prophages possess diversity-generating retroelements implicated in rapid mutation of phage genome loci associated with phage-host and phage-environment interactions and analyze the intricate patterns of retroelement activity. Our study highlights the potential of prophage characterization for elucidating complex molecular mechanisms employed by the phages.

Gut microbiota affects host health and disease. Large-scale cohorts have explored the interactions between the microbiota, host, and environment to reveal the disease-associated microbiota variation. A population-level gut metagenomic cohort is still rare in China. Here, we performed metagenomic sequencing on fecal samples from the CMEC Microbiome Project in Southwest China. In this study, we identified host socioeconomics, diet, lifestyle, and medical measurements that were significantly associated with microbiome function and composition. We revealed extensive novel associations between the host microbiome and common metabolic disorders. Our results provide new insight into associations of gut microbiota with metabolic disorders so as to support the translation of gut microbiome findings into potential clinical practice.

1. This study evaluated the effect of acidified drinking water on the gastrointestinal function and intestinal health of broilers.2. A total of 630 one-day-old male broilers (Arbor Acre) were randomly assigned to one of three treatment groups: drinking water treatment (CON), drinking water + 0.5 ml Selko pH®/L (Selko pH), or + 0.85 ml Forticoat®/L (Forticoat) treated groups. Performance data, gut and digesta samples were collected from the broilers at the age of 21 and 42 d.3. The results showed that acidifying drinking water had no significant effect on body weight or average daily gain (ADG). However, addition of Forticoat significantly increased (p < 0.05) feed conversion ratio (FCR) throughout the experimental period and significantly increased (p < 0.05) pepsin activity on d 21. The Selko pH supplemented drinking water significantly increased (p < 0.05) the relative length of the duodenum and jejunum on d 21. The relative length of the jejunum and caecum on d 42 compared to birds receiving CON. The addition of the Forticoat to drinking water significantly increased (p < 0.05) the relative length of the jejunum and caecum on d 42 than for samples from birds in the CON group. In the caecal chyme, abundance of Blautia, Bifidobasterium, Faecalibacterium, Limosilactobacillus and Akkermania spp. on d 21 were significantly higher (p < 0.05) in the caecum of birds receiving Selko pH than those in CON group and the number of Escherichia Shigella in Selko pH and Forticoat group were significantly lower (p < 0.05).4. Overall, adding Seiko pH and Forticoat to drinking water improved pepsin activity, reduced the number of caecal pathogens, increased the number of beneficial bacteria and improved intestinal health in broilers.

Dairy consumption has been associated with various health outcomes that may be mediated by changes in gut microbiota.

This cross-sectional study investigated the association between the colonic mucosa-associated gut microbiota and the self-reported intake of total dairy, milk, cheese, and yogurt. A total of 97 colonic mucosal biopsies collected from 34 polyp-free individuals were analyzed. Dairy consumption in the past year was assessed using a food frequency questionnaire. The 16S rRNA gene V4 region was amplified and sequenced. Operational taxonomic unit (OTU) classification was performed using the UPARSE and SILVA databases. OTU diversity and relative abundance were compared between lower vs. higher dairy consumption groups. Multivariable negative binomial regression models for panel data were used to estimate the incidence rate ratio and 95% confidence interval for bacterial counts and dairy consumption. False discovery rate-adjusted p values (q value) < 0.05 indicated statistical significance.

Higher total dairy and milk consumption and lower cheese consumption were associated with higher alpha microbial diversity (adjusted p values < 0.05). Higher total dairy and milk consumption was also associated with higher relative abundance of Faecalibacterium. Higher milk consumption was associated with higher relative abundance of Akkermansia. Higher total dairy and cheese consumption was associated with lower relative abundance of Bacteroides.

Dairy consumption may influence host health by modulating the structure and composition of the colonic adherent gut microbiota.