Gastrointestinal symptoms are common during infancy, including infantile colic. Colic can be loosely defined as prolonged and recurrent crying without obvious cause. The cause indeed remains unclear despite much research. Results on infant nutrition are inconclusive, but prior work has linked maternal mental health to infant crying. Recently, several small studies have described associations between gut microbiota and colic. We used a larger cohort to examine the role of the microbiota in infant gastrointestinal health, while also accounting for other biopsychosocial factors. Using fecal 16S rRNA gene amplicon sequencing data from 1,012 infants in the KOALA birth cohort, we examined associations between the 1-month gut microbiota and parent-reported functional gastrointestinal symptoms throughout infancy, including colic, constipation, and cramps. These analyses were adjusted for biopsychosocial factors that were associated with symptoms in a broader analysis involving 2,665 participants. In 257 infants, we also explored associations between breastmilk human milk oligosaccharides (HMOs) and gastrointestinal symptoms. Higher relative abundance of Staphylococcus at one month was associated with less constipation in the first three months of life. Conversely, Ruminococcus gnavus group abundance was associated with more colicky symptoms, particularly between four and seven months. Breastmilk concentrations of the HMOs lacto-N-hexaose (LNH) and lacto-N-neohexaose (LNnH) were associated with less constipation in the first three months. Our results support the conclusion that gut microbiota are relevant in infantile colic and constipation. However more work is needed to elucidate the underlying mechanisms, and explore their interplay with other relevant biopsychosocial factors such as maternal mental health.

Joint inflammation is the most common extraintestinal manifestation of Crohn's disease (CD). Although alterations in the enteric microbiota are described in CD with spondyloarthritis (CD-SpA), it is not known whether distinct taxa serve as markers for clinical subtypes of axial (AxSpA) or peripheral SpA (pSpA) in CD. Moreover, it is not yet known whether these taxa generate a specific systemic IgG response. Here, we sequenced the fecal microbiome from 106 individuals (44 CD, 39 CD-SpA, 14 CD-AxSpA, and 9 healthy controls [HC]). This unique cohort revealed distinct taxonomic compositions of CD and CD-SpA compared to HC and demonstrates that the composition of the CD-AxSpA microbiome is distinct from that of CD-pSpA. Using autologous serum, we identified enteric bacteria recognized by serum IgG and demonstrate differences in the IgG coating index of specific bacterial genera associated with CD-SpA. The IgG coating index of Mediterraneibacter gnavus differentiated patients with CD-pSpA and is positively associated with joint disease activity. This work illustrates divergent microbiome compositions in CD-SpA subtypes, as well as the recognition of distinct enteric bacteria by serum IgG with the potential to serve as a marker of joint inflammation in CD.

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.

Metabolic Associated Fatty Liver Disease (MAFLD) impacts approximately 25% of the global population. Between April 2023 and July 2023, 60 patients with MAFLD, along with 60 age, ethnicity, and sex-matched healthy controls (HCs), were enrolled from the Inner Mongolia Autonomous Region, China. Analysis of gut microbiota composition and plasma metabolic profiles was conducted using metagenome sequencing and LC-MS. LEfSe analysis identified five pivotal species: Eubacterium rectale, Dialister invisus, Pseudoruminococcus massiliensis, GGB3278 SGB4328, and Ruminococcaceae bacteria. In subgroup analysis, Eubacterium rectale tended to increase by more than 2 times and more than double in the non-obese MAFLD group, and MAFLD with moderate hepatic steatosis (HS), respectively. Plasma samples identified 172 metabolites mainly composed of fatty acid metabolites such as propionic acid and butyric acid analogues. Ruminococcaceae bacteria have a strong positive correlation with β-alanine, uric acid, and L-valine. Pseudoruminococcus massiliensis has a strong positive correlation with β-alanine. Combinations of phenomics and metabolomics yielded the highest accuracy (AUC = 0.97) in the MAFLD diagnosis. Combinations of phenomics and metagenomics yielded the highest accuracy (AUC = 0.94) in the prediction of the MAFLD HS progress. Increases in Eubacterium rectale and decreases in Dialister invisus seem to be indicative of MAFLD patients. Eubacterium rectale may predict HS degree of MAFLD and play an important role in the development of non-obese MAFLD. Eubacterium rectale can generate more propionic acid and butyric acid analogues to absorb energy and increase lipid synthesis and ultimately cause MAFLD.

A wide variety of human diseases are associated with loss of microbial diversity in the human gut, inspiring a great interest in the diagnostic or therapeutic potential of the microbiota. However, the ecological forces that drive diversity reduction in disease states remain unclear, rendering it difficult to ascertain the role of the microbiota in disease emergence or severity. One hypothesis to explain this phenomenon is that microbial diversity is diminished as disease states select for microbial populations that are more fit to survive environmental stress caused by inflammation or other host factors. Here, we tested this hypothesis on a large scale, by developing a software framework to quantify the enrichment of microbial metabolisms in complex metagenomes as a function of microbial diversity. We applied this framework to over 400 gut metagenomes from individuals who are healthy or diagnosed with inflammatory bowel disease (IBD). We found that high metabolic independence (HMI) is a distinguishing characteristic of microbial communities associated with individuals diagnosed with IBD. A classifier we trained using the normalized copy numbers of 33 HMI-associated metabolic modules not only distinguished states of health vs IBD, but also tracked the recovery of the gut microbiome following antibiotic treatment, suggesting that HMI is a hallmark of microbial communities in stressed gut environments.

The composition of the microbiota in patients has been shown to correlate with cancer progression and response to therapy, highlighting unique opportunities to improve patient outcomes. In this review, we discuss the challenges and advancements in understanding the chemical mechanisms of specific microbiota species, pathways, and molecules involved in cancer progression and treatment. We also describe the modulation of cancer and immunotherapy by the microbiota, along with approaches for investigating microbiota enzymes and metabolites. Elucidating these specific microbiota mechanisms and molecules should offer new opportunities for developing enhanced diagnostics and therapeutics to improve outcomes for cancer patients. Nonetheless, many microbiota mechanisms remain to be determined and require innovative chemical genetic approaches.

The intestinal microbiota plays a crucial role in maintaining host health by participating in various beneficial functions. However, under certain conditions, it can contribute to the development of inflammatory bowel disease (IBD) and other chronic inflammatory conditions. Importantly, not all commensal microbiota members are drivers of inflammation. A specific subset of commensal bacteria, known as pathobionts, can exhibit pathogenic potential under specific circumstances. Their inflammatory potential is modulated by several factors, including the host's genetic background and the surrounding microbiota. Furthermore, diet has emerged as a critical factor influencing the gut microbiota, with some studies highlighting its role in modulating pathobionts. This review will delve into the role played by pathobionts in chronic intestinal inflammation, in both mouse models as well as in humans, with a focus on the interplay between dietary factors and pathobiont members of the intestinal microbiota. Understanding the complex relationships between diet, pathobionts, and chronic inflammation could pave the way for diet-based therapeutic strategies aimed at managing chronic inflammatory conditions.

The gut microbiota is closely related to the occurrence and development of cancer. However, the characteristics of gut microbiota associated with ovarian tumors remain elusive. In this study, fecal samples were collected from healthy control (HC) group and patients with ovarian tumor (OT) or with other benign tumor (OBT) for 16s rRNA sequencing to determine differential flora in gut microbiota. The composition of gut microbiota in the OT group, including bacterial abundance and diversity, was significantly different form HC and OBT groups. In the OT group, Escherichia_Shigella was markedly higher than in the HC group, while Coprococcus, Fusicatenibacter, Butyricicoccus and Oscillibacter were significantly lower than in HCs. The abundance of Fusicatenibacter, Butyricicoccus, Coprococcus Parasutterella, and Anaerotruncus in the OBT group was distinctly higher than that in the OT group, while the Lachnospiracae_ND3007_group was significantly lower. In addition, in OT patients, ovarian cancer (OC) and benign ovarian tumor (BOT) patients also showed a unique composition of gut microbiota. The random forest model was designed using different bacteria. Compared with HCs, area under curve (AUC) values for BOT and OC groups were 0.77 and 0.86, respectively. These findings suggest that some gut microbiota such as Escherichia_Shigella show a certain ability to distinguish between healthy individuals and patients with OT.

Crohn's disease (CD) is characterized by an inflammatory response to gut microbiota. Macrophages and dendritic cells play an active role in CD inflammation. Specific microbiota have been implicated in the pathogenesis of ileal CD. We investigated the phagocyte-associated microbiome using an unbiased sequencing approach to identify potential pathobionts and elucidate the host response to these microbes.

We collected ileal and colonic mucosal biopsies from CD patients and controls without inflammatory bowel disease (IBD), isolated lamina propria phagocytes (CD11b+ cells), and performed deep RNA sequencing (n = 37). Reads were mapped to the human genome for host gene expression analysis and a prokaryotic database for microbiome taxonomic and metatranscriptomic profiling. Results were confirmed in a second IBD cohort (n = 17). Lysed lamina propria cells were plated for bacterial culturing; isolated colonies underwent whole genome sequencing (n = 11).

Crohn's disease ileal phagocytes contained higher relative abundances of Escherichia coli, Ruminococcus gnavus, and Enterocloster spp. than those from controls. CD phagocyte-associated microbes had increased expression of lipopolysaccharide (LPS) biosynthesis pathways. Phagocytes with a higher pathobiont burden showed increased expression of pro-inflammatory and antimicrobial genes, including PI3 (antimicrobial peptide) and BPIFB1 (LPS-binding molecule). E. coli isolated from the CD lamina propria had more flagellar motility and antibiotic resistance genes than control-derived strains.

Lamina propria resident phagocytes harbor bacterial strains that may act as pathobionts in CD. Our findings shed light on the role of pathobionts and the immune response in CD pathogenesis and suggest new targets for therapies.

In the last three decades, our understanding of how exercise induces oxidative stress has significantly advanced. Plant polysaccharides, such as dietary fibers and resistant starches, have been shown to enhance exercise performance by improving energy metabolism, reducing fatigue, increasing strength and stamina, mitigating oxidative stress post-exercise, facilitating muscle recovery, and aiding in detoxification. Moreover, antioxidants found in plant-based foods play a crucial role in protecting the body against oxidative stress induced by intense physical activity. By scavenging free radicals and reducing oxidative damage, antioxidants can improve exercise endurance, enhance recovery, and support immune function. Furthermore, the interaction between plant polysaccharides and antioxidants in the gut microbiota can lead to synergistic effects on overall health and performance. This review provides a comprehensive overview of the current research on plant polysaccharides and antioxidants in relation to exercise performance and gut health.

The intestine, as a critical interface between the external environment and the internal body, plays a central role in nutrient absorption, immune regulation, and maintaining homeostasis. The intestinal epithelium, composed of specialized epithelial cells, harbors apical anion transporters that primarily mediate the transport of chloride and bicarbonate ions, essential for maintaining electrolyte balance, pH homeostasis, and fluid absorption/secretion. In addition, the intestine hosts a diverse population of gut microbiota that plays a pivotal role in various physiological processes including nutrient metabolism, immune regulation, and maintenance of intestinal barrier integrity, all of which are critical for host gut homeostasis and health. The anion transporters and gut microbiome are intricately interconnected, where alterations in one can trigger changes in the other, leading to compromised barrier integrity and increasing susceptibility to pathophysiological states including gut inflammation. This review focuses on the interplay of key apical anion transporters including Down-Regulated in Adenoma (DRA, SLC26A3), Putative Anion Transporter-1 (PAT1, SLC26A6), and Cystic Fibrosis Transmembrane Conductance Regulator [CFTR, ATP-binding cassette subfamily C member 7 (ABCC7)] with the gut microbiome, barrier integrity, and their relationship to gut inflammation.

To decipher the mechanisms underlying the protective role of the Mediterranean diet (MED) in Crohn's disease (CD), we explored the implications of adherence to MED on CD course, inflammatory markers, and microbial and metabolite composition.

Patients with newly diagnosed CD were recruited and followed prospectively. MED adherence was assessed by repeated food frequency questionnaires (FFQs) using a predefined inflammatory bowel disease Mediterranean diet score (IBDMED score), alongside validated MED adherence screeners. Crohn's disease activity index (CDAI), C-reactive protein, fecal calprotectin, and microbial composition (16S-ribosomal RNA sequencing) were assessed each visit. Baseline serum and fecal samples were analyzed for targeted quantitative metabolomics.

Consecutive patients: 271 (52% men, average age 31 ± 12 years, B1 phenotype 75%). FFQs collected: 636 (range 1-5 FFQs per patient). Adherence to MED was associated with a noncomplicated CD course, and inversely correlated with CDAI, fecal calprotectin, C-reactive protein, and microbial dysbiosis index (all P < .05). Increasing adherence to MED over time correlated with reduced CDAI and inflammatory markers (P < .05). Adherence to MED correlated with a microbial cluster of commensals and short-chain fatty acid producers including Faecalibacterium, and with plant metabolites, vitamin derivatives, and amino acids. Conversely, adherence to MED inversely correlated with a cluster of oral genera, Escherichia coli and Ruminococcus gnavus, known CD-associated species, and with tryptophan metabolites, ceramides, and primary bile acids (false discovery rate < 0.2).

Adherence to MED is associated with beneficial clinical outcomes and decreased inflammatory markers. These may be driven by lower levels of primary bile acids and microbial dysbiosis and a beneficial microbial and metabolite composition. Randomized controlled trials are needed to evaluate the role of MED in CD management.

Advances in understanding the pathogenesis of inflammatory bowel disease (IBD) point toward a key role of the gut microbiome. We review the data describing the changes in the gut microbiome from IBD case-control studies and compare these findings with emerging data from studies of the preclinical phase of IBD. What is apparent is that assessing changes in the composition and function of the gut microbiome during the preclinical phase helps address confounding factors, such as disease activity and drug therapy, which can directly influence the gut microbiome. Understanding these changes in the predisease phase provides a means of predicting IBD in high-risk populations and offers insights into possible mechanisms involved in disease pathogenesis. Finally, we discuss strategies to use this information to design interventions aimed at modulating the microbiome as a means of preventing or delaying the onset of IBD.

The gut microbiota is a diverse ecosystem that significantly impacts human health and disease. This article focuses on how the gut microbiota interacts with inflammatory bowel diseases and colorectal tumors, especially through immune regulation. The gut microbiota plays a role in immune system development and regulation, while the body's immune status can also affect the composition of the microbiota. These microorganisms exert pathogenic effects or correct disease states in gastrointestinal diseases through the actions of toxins and secretions, inhibition of immune responses, DNA damage, regulation of gene expression, and protein synthesis. The microbiota and its metabolites are essential in the development and progression of inflammatory bowel diseases and colorectal tumors. The complexity and bidirectionality of this connection with tumors and inflammation might render it a new therapeutic target. Hence, we explore therapeutic strategies for the gut microbiota, highlighting the potential of probiotics and fecal microbiota transplantation to restore or adjust the microbial community. Additionally, we address the challenges and future research directions in this area concerning inflammatory bowel diseases and colorectal tumors.

This study investigated the longitudinal effects of acute (7-day) and prolonged (3-month) high-altitude exposure on gut microbiota in healthy adult males, addressing the limited data available in human populations. A cohort of 406 healthy adult males was followed, and fecal samples were collected at three time points: baseline at 800 m (406 samples), 7 days after ascending to 4,500 m (406 samples), and 2 weeks post-return to 800 m following 3 months at high altitude (186 samples). High-throughput 16S ribosomal DNA sequencing was employed to analyze microbiota composition and diversity. Results revealed significant changes in alpha- and beta-diversity, with acute high-altitude exposure inducing more pronounced effects compared to prolonged exposure. Specifically, acute exposure increased opportunistic pathogens (Ruminococcus and Oscillibacter) but decreased beneficial short-chain fatty acid producers (Faecalibacterium and Bifidobacterium). Notably, these changes in microbiota persisted even after returning to low altitude, indicating long-term remodeling. Functional analyses revealed substantial changes in metabolic pathways, suggesting microbiota-driven adaptations to energy utilization under high-altitude hypoxic conditions. In summary, acute high-altitude exposure caused dramatic changes in gut microbiota, while prolonged exposure led to structural and functional reshaping. These findings enhance our understanding of how high-altitude environments reshape gut microbiota.

This study is the first to investigate the impact of high-altitude exposure on gut microbiota adaptation in a large-scale longitudinal cohort. It seeks to enhance understanding of how high-altitude environments reshape gut microbiota. Acute exposure to high altitude significantly affected both α-diversity and β-diversity of gut microbiota, with acute exposure causing more pronounced changes than prolonged adaptation, indicating temporary disruptions in microbial communities. Notable shifts in microbial abundance were observed, including increased levels of genera linked to hypoxic stress (e.g., Gemmiger, Ruminococcus, and Parabacteroides) and decreased levels of beneficial bacteria (e.g., Faecalibacterium, Roseburia, and Bifidobacterium), suggesting possible adverse health effects. Functional analysis indicated changes in metabolism-related pathways post-exposure, supporting the idea that high-altitude adaptations involve metabolic adjustments for energy management. These findings enhance understanding of high-altitude physiology, illustrating the role of gut microbiota in hypoxic health.

Gut microbiota may regulate metabolism but is incompletely characterized in pregnancy. Our objective was to investigate the relations using omics techniques.

In a cross-sectional setting, fecal and serum samples of 361 healthy pregnant women with overweight or obesity were analyzed with a combinatorial approach of metagenomics and targeted NMR-based metabolomics, with statistical and machine learning techniques to identify and analyze the extent to which the gut microbiota composition and predicted functions would be reflected in the serum metabolome. We identified five biclusters, each of which consisted of a set of gut microbial species and serum metabolites with correlated abundance profiles. Two of the biclusters included metabolites that have been linked to the cardiovascular health; one was linked with factors known to increase the risk i.e., various sizes of lipoprotein subclasses (VLDL and LDL), subclasses of relative lipoprotein lipid concentrations (VLDL, IDL, and LDL), apolipoprotein B, and an inflammation marker, glycoprotein acetylation. These metabolites were associated with abundances of species such as, Enterocloster bolteae and Ruminococcus gnavus. The second bicluster included metabolites linked with a reduced cardiovascular risk, such as different sizes of HDL (high-density lipoprotein), subclasses for relative lipoprotein lipid concentrations and mean diameter for HDL particles, and fatty acid ratios. These metabolites were associated with abundances of species, such as Bacteroides cellulosilyticus and Alistipes finegoldii. We did not observe any biclusters between predicted pathways and serum metabolites.

Overall, we identified five biclusters of co-abundant gut bacteria and serum metabolites , of which two were linked to pro-atherogenic and anti-atherogenic properties.

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Gov: NCT01922791.

Mediterraneibacter gnavus, also known as Ruminococcus gnavus, is a Gram-positive anaerobic bacterium that resides in the human gut microbiota. Notably, this bacterium plays dual roles in health and disease. On one side it supports nutrient metabolism essential for bodily functions and on the other it contributes to the development of Inflammatory Bowel Disease (IBD) and other gastrointestinal disorders. R. gnavus strain RJX1120 is an encapsulated strain and has been linked to develop IBD. Despite the advances made on its role in gut homeostasis, limited information is available on strain-specific virulence factors, metabolic pathways, and regulatory mechanisms. The study of such aspects is crucial to make microbiota-targeted therapy and understand its implications in host health. A multi-epitope vaccine against R. gnavus strain RJX1120 was designed using reverse vaccinology-based subtractive proteomics approach. Among the 3,219 proteins identified in the R. gnavus strain RJX1120, two critical virulent and antigenic proteins, a Single-stranded DNA-binding protein SSB (A0A2N5PT08) and Cell division ATP-binding protein FtsE (A0A2N5NK05) were screened and identified as potential targets. The predicted B-cell and T-cell epitopes from these proteins were screened for essential immunological properties such as antigenicity, allergenicity, solubility, MHC binding affinity, and toxicity. Epitopes chosen were cross-linked using suitable spacers and an adjuvant to develop a multi-epitope vaccine. Structural refinement of the construct revealed that 95.7% of the amino acid residues were located in favored regions, indicating a high-quality structural model. Molecular docking analysis demonstrated a robust interaction between the vaccine construct and the human Toll-like receptor 4 (TLR4), with a binding energy of -1277.0 kcal/mol. The results of molecular dynamics simulations further confirmed the stability of the vaccine-receptor complex under physiological conditions. In silico cloning of the vaccine construct yielded a GC content of 48% and a Codon Adaptation Index (CAI) value of 1.0, indicating optimal expression in the host system. These results indicate the possibility of the designed vaccine construct as a candidate for the prevention of R. gnavus-associated diseases. However, experimental validation is required to confirm its immunogenicity and protective efficacy.

The aetiology of Crohn's disease, a chronic inflammatory bowel disease, is multifactorial and not completely understood. However, the association with gut dysbiosis is well-established, and manipulation of the gut microbiota has gained interest as a treatment strategy. This study aimed to investigate the effects of the probiotic strain Bifidobacterium breve, Bif195™ (Bif195) on intestinal inflammation, symptoms, and the gut microbiome composition in patients with small intestinal Crohn's disease.

This was a randomised, double-blind, placebo-controlled trial. Thirty-three patients with small intestinal Crohn's disease were assigned to eight weeks of treatment with Bif195 or placebo (1:1). The primary outcome was changes in bowel wall thickness measured by intestinal ultrasonography. Other outcomes were changes in symptom severity, quality of life, faecal calprotectin, fatigue, and specific inflammatory parameters on ultrasonography. Changes in the microbiome composition were also examined.

Bif195 did not affect the bowel wall thickness in the small intestine compared to placebo. Nor did we observe effects on secondary or clinical explorative outcomes. Analysis of the gut microbiome showed that the relative abundance of B. breve rose during the intervention in the Bif195 group, but the result was statistically non-significant. Surprisingly, we observed a clustering of baseline microbiome data into two groups that differed in several aspects including a statistically significant difference in the incidence of previous bowel resections among the participants. Furthermore, changes in symptom scores after eight weeks of intervention were significantly different across the two microbiome groups, with an interaction effect of p = 0.04.

Eight weeks of treatment with Bif195 did not affect clinical outcomes for Crohn's disease. However, variations in baseline microbiome data influenced the results. This underscores the importance of assessing baseline microbiome data in intervention studies in Crohn's disease.

gov NCT04842149.

Immune thrombocytopenia during pregnancy (PITP) is the most common cause of platelet reduction in early and mid-pregnancy. However, the pathogenesis of PITP is still unclear.

To determine the characteristics of bone marrow mesenchymal stem cells (BM-MSCs) in PITP patients and to explore the associations between metabolites, the gut microbiota, and BM-MSCs in PITP.

The characteristics of BM-MSCs were detected through in vitro and in vivo experiments. Nontargeted metabolomics was used to screen metabolites. The features of the gut microbiota were analyzed by 16S rDNA sequencing. PITP and fecal microbiota transplantation (FMT) mouse model were established to explore the associations between metabolites, gut microbiota, and BM-MSCs.

BM-MSCs from PITP patients had significant senescence and apoptosis, as well as impaired immunoregulatory function. Metabolomic analysis indicated that progesterone was the most significant specific metabolite in PITP patients. In vivo studies showed that progesterone mediated MSC injury. Further analysis of the gut microbiota and FMT experiments revealed that progesterone mediated BM-MSCs injury by regulating the composition of the gut microbiota in PITP. RNA sequencing analysis of BM-MSCs from FMT mice revealed abnormal expression of genes related to cell aging and the NOD-like receptor signaling pathway.

In conclusion, BM-MSCs in the PITP were significantly impaired, which was associated with increased progesterone and changes in the gut microbiota regulated by progesterone. Intervening with the gut microbiota may become a new treatment for PITP.

Sleep is an essential homeostatic process that undergoes dynamic changes throughout the lifespan, with distinct life stages predisposed to specific sleep pathologies. Similarly, the gut microbiome also varies with age, with different signatures associated with health and disease in the latest decades of life. Emerging research has shown significant cross-talk between the gut microbiota and the brain through several pathways, suggesting the microbiota may influence sleep, though the specific mechanisms remain to be elucidated. Here, we critically examine the existing literature on the potential impacts of the gut microbiome on sleep and how this relationship varies across adulthood. We suggest that age-related shifts in gut microbiome composition and immune function may, in part, drive age-related changes in sleep. We conclude with an outlook on the therapeutic potential of microbiome-targeted interventions aimed at improving sleep across adulthood, particularly for individuals experiencing high stress or with sleep complaints.

Rheumatic Heart Disease (RHD) remains a significant health burden, particularly in regions with scarce healthcare resources, research on its immunological aspects remains insufficient. This study employed a two-sample Mendelian Randomization approach, utilizing GWAS data from the largest available datasets for gut microbiota and immune cells as exposures, with outcome data for Rheumatic Valve Diseases (RVD) and Rheumatic Heart Disease affecting other parts of the heart (RHD-other) obtained from the FinnGen study. The primary analytical method was the Inverse Variance Weighted (IVW) approach, complemented by heterogeneity analyses and MR-Egger regression to assess horizontal pleiotropy. Furthermore, a two-step mediation analysis was conducted to investigate the potential mediating role of immune cells in the association between gut microbiota and RHD. This study revealed significant inverse associations between gut microbiota abundance and Rheumatic Heart Disease (RHD) risk. Specifically, the gut abundance of genus Blautia was negatively correlated with RHD-other risk (P_IVW: 0.00932, OR [95%CI]: 0.000734[3.22e-06, 0.16937]), and genus Ruminococcaceae UCG005 showed a similar negative association (P_IVW: 0.038, OR [95%CI]: 0.165[0.02994, 0.90811]). Additionally, the proportions of CD4-CD8- T cell %leukocyte and CD4-CD8- T cell %T cell were inversely related to RHD-other risk (P_IVW: 0.02222, OR [95%CI]: 5.08027 [1.26133, 20.46191] and P: 0.01601, OR[95%CI]: 6.55576 [1.4196, 30.27582], respectively). Moreover, IgD on IgD + CD24 + B cells was found to be negatively correlated with RHD-other risk (P_IVW: 0.01867, OR [95%CI]: 2.17171 [1.1380, 4.14443]). The study also highlighted the protective effects of gut microbiota through mediation analyses: Blautia's impact via IgD on IgD + CD24 + B cells showed a mediation proportion of 8.62514%; Ruminococcaceae UCG005's influence via CD4-CD8- T cell %T cell and CD4-CD8- T cell %leukocyte resulted in mediation proportions of 35.25817% and 30.86827%, respectively. Significant inverse associations were observed between gut microbiota abundance and risk of Rheumatic Heart Disease (RHD), with specific findings for Rheumatic Valve Disease (RVD) and RHD affecting other parts of the heart (RHD-other). For RHD-other, higher abundance of Blautia (OR: 0.0007, 95% CI: 3.22e-06 to 0.169, p = 0.009) and Ruminococcaceae UCG005 (OR: 0.165, 95% CI: 0.030 to 0.908, p = 0.038) were associated with lower risk. Additionally, lower proportions of CD4-CD8- T cells (%leukocyte and %T cell) and IgD on IgD + CD24 + B cells were inversely related to RHD-other risk (ORs: 5.08 and 6.56, p = 0.022 and p = 0.016, respectively). For RVD, higher abundance of Candidatus Soleaferrea was protective (OR: 0.670, 95% CI: 0.460 to 0.976, p = 0.037), while higher levels of CD11c on granulocytes were associated with increased risk (OR: 1.310, 95% CI: 1.023 to 1.679, p = 0.032). Mediation analyses indicated that gut microbiota influence RHD risk through distinct immune pathways, with Blautia affecting RHD-other via IgD on B cells (8.62% mediation), Ruminococcaceae UCG005 via CD4-CD8- T cells (%T cell: 35.26%, %leukocyte: 30.87%). Genus Candidatus Soleaferrea affecting RVD through CD11c on granulocyte (15.01% mediation). The study concludes that higher gut abundance of Candidatus Soleaferrea protects against RVD through the mechanism involving CD11c on granulocytes. Additionally, Blautia exerts a protective effect against RHD-other through its influence on IgD on IgD + CD24 + B cells. Similarly, the abundance of genus Ruminococcaceae UCG005 provides protection against RHD-other by influencing CD4-CD8- T cell %T cell and CD4-CD8- T cell %leukocyte.

Diverticular disease is a common and morbid complex phenotype influenced by both innate and environmental risk factors. We performed the largest genome-wide association study meta-analysis for diverticular disease, identifying 126 novel loci. Employing multiple downstream analytic strategies, including tissue and pathway enrichment, statistical fine-mapping, allele-specific expression, protein quantitative trait loci and drug-target investigations, and linkage disequilibrium score regression, we prioritized causal genes and produced several lines of evidence linking diverticular disease to connective tissue biology and colonic motility. We substantiated these findings by integrating single-cell RNA sequencing data, showing that prioritized diverticular disease-associated genes are enriched for expression in colonic smooth muscle, fibroblasts, and interstitial cells of Cajal. In quantitative analysis of surgical specimens, we found a substantial reduction in the density of elastin present in the sigmoid colon in severe diverticulitis.

There is mounting evidence for the involvement of the immune system, neuroinflammation and disturbed gut microbiota, or dysbiosis, in attention-deficit/hyperactivity disorder (ADHD). Gut dysbiosis is strongly implicated in many physical, autoimmune, neurological, and neuropsychiatric conditions, however knowledge of its particular pathogenic role in ADHD is sparse. As such, this narrative review examines and synthesizes the available evidence related to inflammation, dysbiosis, and neural processes in ADHD. Minimal differences in microbiota diversity measures between cases and controls were found, however many relative abundance differences were observed at all classification levels (phylum to strain). Compositional differences of taxa important to key gut-brain axis pathways, in particular Bacteroides species and Faecalibacterium, may contribute to inflammation, brain functioning differences, and symptoms, in ADHD. We have identified one possible model of ADHD etiopathogenesis involving systemic inflammation, an impaired blood-brain barrier, and neural disturbances as downstream consequences of gut dysbiosis. Nevertheless, studies conducted to date have varied degrees of methodological rigour and involve diverse participant characteristics and analytical techniques, highlighting a need for additional research.

Ulcerative colitis (UC) is a chronic and recurrent gastrointestinal disease that affects millions of humans worldwide and imposes a huge social and economic burden. It is necessary to find safe and efficient drugs for preventing and treating UC. The aim of this study was to determine whether ganoderic acid (GA), the main bioactive components of Ganoderma lucidum, has preventive and therapeutic effect on UC in a dextran sulfate sodium (DSS)-induced UC mouse model. Our experimental results showed that GA significantly ameliorated the body weight loss and disease activity index (DAI) of UC mice. GA significantly restored 11% of the colon length and 69% of the spleen index compared to UC mice. GA significantly decreased the intestinal inflammatory response and improved the barrier function of the intestine by upregulating the tight junction proteins Zonula occludens-1 (ZO-1), occludin and claudin-1. A co-housing experiment showed that gut microbiota accounted for the therapeutic activity of GA on UC, which was confirmed by fecal microbiota transplantation from GA-treated mice to the UC mice. Furthermore, 16S rDNA high-throughput sequencing of fecal bacteria showed that GA significantly enriched the abundance of Lactobacillus, Oscillospira, Odoribacter and Ruminococcus, which were positively correlated with colon length. Furthermore, this study found the functional metabolites, including Indole-3-acetaldehyde (IAAld), Glutamine (Gln) and Glutathione (GSH), reduced barrier damage in the Caco-2 cell model. In conclusion, this study suggests that GA could ameliorate UC by improving intestinal barrier function via modulating gut microbiota and associated metabolites.

Perturbations in the intestinal microbiome are strongly linked to the pathogenesis of inflammatory bowel disease (IBD). Bacteria, fungi and viruses all make up part of a complex multi-kingdom community colonizing the gastrointestinal tract, often referred to as the gut microbiome. They can exert various effects on the host that can contribute to an inflammatory state. Advances in screening, multiomics and experimental approaches have revealed insights into host-microbiota interactions in IBD and have identified numerous mechanisms through which the microbiota and its metabolites can exert a major influence on the gastrointestinal tract. Looking into the future, the microbiome and microbiota-associated processes will be likely to provide unparalleled opportunities for novel diagnostic, therapeutic and diet-inspired solutions for the management of IBD through harnessing rationally designed microbial communities, powerful bacterial and fungal metabolites, individually or in combination, to foster intestinal health. In this Review, we examine the current understanding of the cross-kingdom gut microbiome in IBD, focusing on bacterial and fungal components and metabolites. We examine therapeutic and diagnostic opportunities, the microbial metabolism, immunity, neuroimmunology and microbiome-inspired interventions to link mechanisms of disease and identify novel research and therapeutic opportunities for IBD.

Feeding HC diets has been found to induce metabolic dysregulation in the colon. However, the mechanisms by which changes in colonic flora and metabolites damage the colonic epithelium are poorly studied. Therefore, the present experiment used a multi-omics technique to investigate the mechanism of colonic injury induced by high-concentrate diets in lambs. Twelve male Dumont lambs were randomly split into two groups: a low-concentrate diet (LC = concentrate/forage = 30:70) group and a high-concentrate diet (HC = concentrate/forage = 70:30) group. The results showed that the HC group presented significantly increased lipopolysaccharide (LPS) concentrations in the colonic epithelium and significantly decreased serum total cholesterol (TC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels (p < 0.05), which led to cavities and inflammatory cell infiltration in the colonic epithelium. The HC group had significantly lower pH and less VFAs in colon contents, as well as a significantly increased abundance of bacteria of the genera [Eubacterium]_coprostanoligenes_group, Rikenellaceae_RC9_gut_group, Treponema, Clostridia_UCG-014, Alistipes, Ruminococcus, Christensenellaceae_R-7_group, UCG-002, Bacteroidales_RF16_group and Lachnospiraceae_AC2044_group compared to the LC diet group. These microorganisms significantly increased the level of metabolites of cholic acid, chenodeoxycholic acid, LysoPA (P-16:0/0:0), methapyrilene, and fusaric acid. A transcriptome analysis showed that cytokine-cytokine receptor interaction, glutathione metabolism, and the peroxisome signaling pathway were downregulated in the colon epithelium of the lambs fed the HC diet. Therefore, the HC diet caused epithelial inflammation and oxidative damage by affecting the interaction between the microbial flora of the colon and metabolites and the host epithelium, which eventually disrupted colon homeostasis and had a negative impact on sheep health.

Chronic low back pain (LBP) is a significant global health concern, often linked to vertebral bone marrow lesions (BML), particularly fatty replacement (FR). This study aims to explore the relationship between the gut microbiome, serum metabolome, and FR in chronic LBP patients.

Serum metabolomic profiling and gut microbiome analysis were conducted in chronic LBP patients with and without FR (LBP + FR, n = 40; LBP, n = 40) and Healthy Controls (HC, n = 31). The study investigates alterations in branched-chain amino acids (BCAAs) levels and identifies key microbial species associated with BCAA metabolism. In vitro experiments elucidate the role of BCAAs in adipogenesis of bone marrow mesenchymal stem cells (BM-MSCs) via the SIRT4 pathway.

Chronic LBP patients with FR exhibit depleted BCAA levels in their serum metabolome, along with alterations in the gut microbiome. Specific microbial species, including Ruminococcus gnavus, Roseburia hominis, and Lachnospiraceae bacterium 8 1 57FAA, are identified as influential in BCAA metabolism and BM-MSCs metabolism. In vitro experiments demonstrate the ability of BCAAs to induce BM-MSCs adipogenesis through SIRT4 pathway activation.

This study sheds light on the intricate relationship between the disturbed gut ecosystem, serum metabolites, and FR in chronic LBP. Dysbiosis in the gut microbiome may contribute to altered BCAA degradation, subsequently promoting BM-MSCs adipogenesis and FR. Understanding these interactions provides insights for targeted therapeutic strategies to mitigate chronic LBP associated with FR by restoring gut microbial balance and modulating serum metabolite profiles.

Metabolic disease is rising along with both global industrialization and the use of new commercial, agricultural, and industrial chemicals and food additives. Exposure to these compounds may contribute to aspects of metabolic diseases such as obesity, diabetes, and fatty liver disease. Ingesting compounds in the food supply is a key route of human exposure, resulting in the interaction between toxicants or additives and the intestinal microbiota. Toxicants can influence the composition and function of the gut microbiota, and these microbes can metabolize and transform toxicants and food additives. Microbe-toxicant interactions in the intestine can alter host mucosal barrier function, immunity, and metabolism, which may contribute to the risk or severity of metabolic disease development. Targeting the connection between toxicants, food, and immunity in the gut using strategies such as fermentable fiber (i.e., inulin) may mitigate some of the effects of these compounds on host metabolism. Understanding causative factors in the microbe-host relationship that promote toxicant-induced dysmetabolism is an important goal. This review highlights the role of common toxicants (i.e., persistent organic pollutants, pesticides, and fungicides) and food additives (emulsifiers and artificial sweeteners) found in our food supply that alter the gut microbiota and promote metabolic disease development.

Steatotic liver disease (SLD) is a leading cause of chronic liver disease worldwide. As SLD pathogenesis has been linked to gut microbiome alterations, we aimed to identify SLD-associated gut microbiome features early in SLD development by utilising a highly characterised cohort of community-dwelling younger adults.

At age 27 years, 588 participants of the Raine Study Generation 2 underwent cross-sectional assessment. Hepatic steatosis was quantified using a validated magnetic resonance imaging (MRI) volumetric liver fat fraction (VLFF) equation (HepaFat). Of the 588 participants, 488 (83%) were classified as having 'no SLD' (VLFF ≤ 3.55%), 76 (12.9%) with 'mild-moderate' SLD (VLFF: 3.56%-13.4%) and 24 (4.10%) with 'severe' SLD (VLFF > 13.4%). Stool microbiome profiling identified an association between severe SLD and lower microbiota alpha diversity (observed features [p = 0.015], Pielou evenness [p = 0.001] and Shannon diversity [p = 0.002]) compared to no SLD. Faecal microbiota composition differed significantly between no SLD and both mild-moderate (p = 0.004) and severe SLD groups (p = 0.001). There was no significant difference in microbiota dispersion between SLD groups. Reduced relative abundance of short-chain fatty acid producing bacteria, and higher levels of proinflammatory bacterial taxa, were both significantly associated with severe SLD (q < 0.05).

SLD in younger adults is associated with reduced intestinal microbial diversity and a pattern of bacterial taxa depletion that is consistent with other chronic inflammatory conditions. Our characterisation of gut microbiome characteristics in early SLD development provides a potential basis for risk identification and reduction.

The Raine Study is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617001599369).

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation that affects multiple organs, with its prevalence varying by ethnicity. Intestinal dysbiosis has been observed in both SLE patients and murine models. Additionally, intestinal barrier impairment is thought to contribute to the ability of pathobionts to evade and breach immune defenses, resulting in antigen cross-reactivity, microbial translocation, subsequent immune activation, and, ultimately, multiple organ failure. Since the detailed mechanisms underlying these processes are difficult to examine using human samples, murine models are crucial. Various SLE murine models, including genetically modified spontaneous and inducible murine models, offer insights into pathobionts and how they dysregulate systemic immune systems. Furthermore, since microbial metabolites modulate systemic immune responses, bacteria and their metabolites can be targeted for treatment. Based on human and mouse research insights, this review examines how lupus pathobionts trigger intestinal and systemic immune dysregulation. Therapeutic approaches, such as fecal microbiota transplantation and dietary adjustments, show potential as cost-effective and safe methods for preventing and treating SLE. Understanding the complex interactions between the microbiota, host factors, and immune dysregulation is essential for developing novel, personalized therapies to tackle this multifaceted disease.

Colorectal polyps serve as the primary precursors for colorectal cancer. A close relationship has been observed between colorectal polyps and gut microbiota. However, the composition and role of the microbiome associated with tubular adenoma are not well understood. In this study, we prospectively evaluated alterations in gut microbiota among patients with colorectal polyps. A total of 60 subjects were enrolled in this study, including 30 patients with colorectal polyps (CP group) and 30 healthy controls (control group). The 16S rRNA sequencing was employed to characterize the gut microbiome in fecal samples. The results revealed that the beta diversity of the gut microbiota in the CP group significantly differs from that of the control group (p = 0.001). At the phylum level, the relative abundance of Bacteroides, Fusobacteria, and Proteobacteria was higher in the CP group compared to the control group (p < 0.05), whereas the relative abundance of Actinobacteria was higher in the control group in comparison to the CP group (p < 0.05). At the genus level, the abundance of Bacteroides increased in the CP group (p < 0.05), while Bifidobacterium declined in the CP group (p < 0.05). At the species level, the abundance of Clostridium perfringens, unidentified_Bacteroides, unidentified_Dorea, Escherichia coli, Clostridium ramosum, and Ruminococcus gnavus was higher (p < 0.05), whereas the abundance of Bifidobacterium adolescentis, unclassified_Bifidobacterium, Bifidobacterium longum, Faecalibacterium prausnitzii, and unidentified_Bifidobacterium is lower in CP group compared to the control group (p < 0.05). There was a structural imbalance in the composition of intestinal colonization flora for CP patients, characterized by a decrease in beneficial bacteria and an increase in harmful bacteria. Escherichia, Shigella, and Bacteroides may serve as promising biomarkers for early detection of colorectal polyps.

T-2 toxin is one of the most toxic A trichothecene mycotoxins prevalent in the environment and food chain, which brings severe health hazards to both animals and humans and it can significantly damage immune function. In this study, we comprehensively explained the impact of T-2 toxin on the spleen through gut microbiota-spleen axis by integrating the transcriptome and microbiome. Our results revealed that dietary T-2 toxin ≥ 1.0 mg/kg exposure significantly inhibited the growth performance and caused spleen injury in broilers chicks, accompanied by oxidative stress and histopathological damage. Cecal microbiome analysis suggested that T-2 toxin exposure caused gut microbial dysbiosis, especially leading to the decrease of some beneficial bacteria genera that enhanced gut barrier and reduced inflammation, including Blautia, Coprococcus, Lachnospira and Anaerostipes belonging to Lachnospiraceae family. Transcriptome analysis suggested that T-2 toxin exposure directly caused splenic inflammation and immune-related signaling, such as cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, NOD-like receptor signaling pathway and JAK-STAT signaling pathway. Furthermore, by integrating the transcriptome and microbiome analysis, we found that spleen damage induced by T-2 toxin was associated with the abnormal activation of IL-6/JAK/STAT1 signaling pathway-mediated inflammation and apoptosis, which was further verified by western bolt analysis. Notably, dietary selenium supplementation could protect chicks from T-2 toxin-induced adverse effects on growth performance and spleen injury by inhibiting the expression of the IL-6/JAK/STAT1 signaling-related genes. In summary, our findings provided new insights into the immunotoxicity mechanisms of T-2 toxin in the chickens' spleen and highlighted the potential of selenium to alleviate T-2 toxin-induced immunotoxicity.

Knowledge graphs have been a useful tool for many biomedical applications because of their effective representation of biological concepts. Plentiful evidence exists linking the gut microbiome to disease in a correlative context, but uncovering the mechanistic explanation for those associations remains a challenge. Here we demonstrate the potential of knowledge graphs to hypothesize plausible mechanistic accounts of host-microbe interactions in disease. We have constructed a knowledge graph of linked microbes, genes and metabolites called MGMLink, and, using a shortest path or template-based search through the graph and a novel path-prioritization methodology based on the structure of the knowledge graph, we show that this knowledge supports inference of mechanistic hypotheses that explain observed relationships between microbes and disease phenotypes. We discuss specific applications of this methodology in inflammatory bowel disease and Parkinson's disease. This approach enables mechanistic hypotheses surrounding the complex interactions between gut microbes and disease to be generated in a scalable and comprehensive manner.