Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), can seriously impact patients' quality of life. Sodium butyrate (NaB), a product of dietary fiber fermentation, has been shown to alleviate IBD symptoms. Some studies have shown that it is related to ferroptosis. However, the precise mechanism linking NaB, IBD, and ferroptosis is not clear.

This study aimed to demonstrate that NaB suppresses ferroptosis, thereby alleviating inflammatory bowel disease (IBD) through modulation of the extracellular regulated protein kinases/signal transducer and activator of transcription 3 (ERK/STAT3) signaling pathway and intestinal flora.

An IBD model was established using 2.5% (w/v) dextran sulfate sodium (DSS). Mice were orally administered low-dose NaB, high-dose NaB , or 5-aminosalicylic acid (5-ASA). Ferroptosis-related molecules were measured using specific kits, and western blotting (WB) and real-time polymerase chain reaction (RT-qPCR) were used to determine the levels of the target molecules.

NaB alleviated symptoms in IBD mice, including reduced weight loss, prolonged colon length, reduced disease activity index (DAI), and reduced spleen index and mRNA expression of inflammatory factors. Additionally, NaB reduced the content of Fe2+ and myeloperoxidase (MPO) and increased the content of GSH and the activity of superoxide dismutase (SOD), which reflected NaB-inhibited ferroptosis. Moreover, western blotting showed that NaB enhanced STAT3 and ERK phosphorylation. In addition, NaB regulates the composition and functions of flora related to IBD.

NaB alleviates IBD by inhibiting ferroptosis and modulating ERK/STAT3 signaling and the intestinal flora.

Recent sets of evidence have described profiles of 16S rDNA sequences in host tissues, notably in fat pads that are significantly overrepresented and can serve as signatures of metabolic disease. However, these recent and original observations need to be further detailed and functionally defined. Here, using state-of-the-art targeted DNA sequencing and discriminant predictive approaches, we describe, from the longitudinal FLORINASH cohort of patients who underwent bariatric surgery, visceral, and subcutaneous fat pad-specific bacterial 16SrRNA signatures. The corresponding Porphyromonadaceae, Campylobacteraceae, Prevotellaceae, Actimomycetaceae, Veillonellaceae, Anaerivoracaceae, Fusobacteriaceae, and the Clostridium family XI 16SrRNA DNA segment profiles are signatures of the subcutaneous adipose depot while Pseudomonadaceae and Micrococcacecae, 16SrRNA DNA sequence profiles characterize the visceral adipose depot. In addition, we have further identified that a specific pre-bariatric surgery adipose tissue bacterial DNA signature predicts the efficacy of body weight loss in obese patients 5-10 years after the surgery. 16SrRNA signatures discriminate (ROC ~ 1) the patients who did not maintain bodyweight loss and those who did. Second, from the 16SrRNA sequences we infer potential pathways suggestive of catabolic biochemical activities that could be signatures of subcutaneous adipose depots that predict body weight loss.

The interplay between bile acids (BAs) and metabolic diseases has gained importance in recent years, with a variety of studies investigating their relationship with diverging results. Therefore, in the present study we performed a detailed analysis of BA metabolism in 492 subjects with different metabolic phenotypes. Besides microbiomics and metabolomics this investigation included in silico analysis of community metabolism to examine metabolic interchange between different microbes as well as microbes and the human host. Our findings revealed distinct changes in the BA profiles of patients with diabetes and prediabetes, whereas obesity alone had no influence on circulating BAs. Impaired glycemic control led to increased circulating BAs, a shift toward more secondary BAs, and an increase in the ratio of glycine to taurine-conjugated BAs. Additional analyses revealed that the ratio of glycine to taurine conjugation demonstrated variations between the single BAs, cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA), regardless of the metabolic status, with CA having a higher fraction of taurine conjugation. Furthermore, we found that microbiome alterations are associated with BAs, independent of diabetes or obesity. Analysis of microbial community metabolism revealed differential relative pathway abundance in relation to diabetes, particularly those related to membrane and polyamine synthesis. Increased bacterial cross-feeding of polyamines, galactose, and D-arabinose also coincided with an increase in BA. Notably, our serum metabolome analysis mirrored several of the previously in silico predicted exchanged metabolites, especially amino acid metabolism. Therefore, targeting BA metabolism may be a future approach for the treatment of metabolic diseases, especially prediabetes and type 2 diabetes.

Next-generation live biotherapeutics are promising to aid the treatment of obesity and metabolic diseases. Here, we reported a novel anti-obesity probiotic candidate, Roseburia hominis, that was depleted in stool samples of obese subjects compared with lean controls, and its abundance was negatively correlated with body mass index and serum triglycerides. Supplementation of R. hominis prevented body weight gain and disorders of glucose and lipid metabolism, prevented fatty liver, inhibited white adipose tissue expansion and brown adipose tissue whitening in mice fed with high-fat diet, and boosted the abundance of lean-related species. The effects of R. hominis could be partially attributed to the production of nicotinamide riboside and upregulation of the Sirtuin1/mTOR signaling pathway. These results indicated that R. hominis is a promising candidate for the development of next-generation live biotherapeutics for the prevention of obesity and metabolic diseases.

Autoimmune rheumatic diseases (ARDs) are a heterogeneous group of conditions characterized by excessive and misdirected immune responses against the body's own musculoskeletal tissues. Their exact aetiology remains unclear, with genetic, demographic, behavioural and environmental factors implicated in disease onset. One prominent hypothesis for the initial breach of immune tolerance (leading to autoimmunity) is molecular mimicry, which describes structural or sequence similarities between human and microbial proteins (mimotopes). This similarity can lead to cross-reactive antibodies and T-cell receptors, resulting in an immune response against autoantigens. Both commensal microbes in the human microbiome and pathogens can trigger molecular mimicry, thereby potentially contributing to the onset of ARDs. In this review, we focus on the role of molecular mimicry in the onset of rheumatoid arthritis and systemic lupus erythematosus. Moreover, implications of molecular mimicry are also briefly discussed for ankylosing spondylitis, systemic sclerosis and myositis.

The importance of the intestinal microbita in a multitude of physiological processes is well-evidenced. These include metabolism of nutrients and xenobiotics, biosynthesis of vitamin K and vitamin B12, immunomodulation, maintenance of the gut mucosal barrier integrity and protection against some pathogens. Interindividual differences in the intestinal microbiota composition have impacts on health. The bioavailability and activity of some pharmaceuticals are heavily influenced by interindividual variability in metabolism, which has a genetic basis. This variability, primarily occurring in the liver but also in the intestine, has been studied extensively. Despite the advancement of this field - pharmacogenetics - its integration into clinical practice remains limited for reasons discussed herein. This highlights the even greater challenge of applying emerging knowledge on variability in the gut microbiota to drug therapy. However, ignoring these opportunities would be a mistake. While clinical applications of microbiota-guided drug therapy are currently absent and the ideas in this article are largely theoretical, research is uncovering that in cases where a substantial portion of a drug or its metabolites reaches the colon, or where drugs are formulated for colonic delivery, the gut microbiota can significantly affect drug metabolism and activity. Greater focus should be placed on research into how interindividual variability in the intestinal microbiome can modify pharmaceutical bioavailability and activity. This article is deliberately speculative and exploratory but proposes that, though there are still no clinical examples of microbiome-guided drug therapy, these interactions could afford opportunities for improvements in personalised medicine and also for drug design.

Biological factors affect the human microbiome, highlighting the need for reasonably estimating sample sizes in future population studies.

We assessed the temporal stability of fecal microbiome diversity, species composition, and genes and functional pathways through shallow shotgun metagenome sequencing. Using intraclass correlation coefficients (ICC), we measured biological variability over 6 months. We estimated case numbers for 1:1 or 1:3 matched case-control studies, considering significance levels of 0.05 and 0.001 with 80% power, based on the collected fecal specimens per participant.

The fecal microbiome's temporal stability over 6 months varied (ICC < 0.6) for most alpha and beta diversity metrics. Heterogeneity was seen in species, genes, and pathways stability (ICC, 0.0-0.9). Detecting an OR of 1.5 per SD required 1,000 to 5,000 cases (0.05 significance for alpha and beta; 0.001 for species, genes, and pathways) with equal cases and controls. Low-prevalence species needed 15,102 cases, and high-prevalence species required 3,527. Similar needs applied to genes and pathways. In a 1:3 matched case-control study with one fecal specimen, 10,068 cases were needed for low-prevalence species and 2,351 for high-prevalence species. For ORs of 1.5 with multiple specimens, cases needed for low-prevalence species were 15,102 (one specimen), 8,267 (two specimens), and 5,989 (three specimens).

Detecting disease associations requires a large number of cases. Repeating prediagnostic samples and matching cases to more controls could decrease the needed number of cases for such detections.

Our results will help future epidemiologic study designs and implement well-powered microbiome studies.

Preconceptional and maternal obesity are well-known risk factors for pregnancy and fetal complications including gestational diabetes, hypertensive disorders, and macrosomia. Maternal obesity is associated with offspring obesity and increased healthcare costs. To disrupt the cycle of obesity, we aim to investigate the impact of the composition of the maternal microbiota (bacteria and viruses) throughout preconception and pregnancy and the associations with the immune responses and one-carbon metabolism (1-CM) as an underlying mechanism in the pathophysiology of increased adverse pregnancy outcomes in maternal obesity.

The PROMOTE study is a subcohort of the Rotterdam Periconceptional Cohort, a hospital-based observational cohort study. We will include 70 women per BMI group: ≥ 30 kg/m2 or 18.5-25 kg/m2, at different time points in each group: 10 preconceptional, 50 in the first trimester (with longitudinal follow-up during pregnancy, delivery and postpartum) and 10 in the third trimester of pregnancy. Which makes a total of 140 inclusions. Vaginal and rectal bacteriome, virome, and blood samples are collected. In the third trimester inclusions, only faecal samples are collected. Microbiota samples will be analysed using 16S rRNA sequencing. Bacteriome and virome profiles are compared between the BMI subgroups, associations with general immune responses and 1-CM markers will be shown.

ClinicalTrials.gov (NCT05754645).

Dyslipidemia is a major risk factor for cardiovascular diseases and is influenced by genetic and environmental factors, including diet. Emerging research suggests a link between the gut microbiome and metabolic disorders. While the connection between the gut microbiota and dyslipidemia is well documented, the specific relationship between oral bacteria and dyslipidemia has not been thoroughly investigated. This study aimed to identify oral bacterial species associated with dyslipidemia in a community-based Japanese population. We conducted a metagenomic analysis on tongue coating samples from 763 participants in the Iwaki Health Promotion Project, which were collected during health checkups in 2017 and 2019. Dyslipidemia was diagnosed using standard lipid level criteria. The oral microbiome was analyzed via 16S rDNA amplicon sequencing. Statistical analyses included multiple regression and β diversity assessments. Our analysis revealed that the abundances of several bacterial genera, including Veillonella, Atopobium, Stomatobaculum, Tanneralla, and Megasphaera, are significantly associated with dyslipidemia. A higher relative abundance of Megasphaera was specifically observed in individuals with dyslipidemia. Moreover, Megasphaera abundance was closely associated with the onset of dyslipidemia (P = 0.038, odds ratio: 1.005, 95% confidence interval: 1.000-1.009), suggesting its role in metabolic regulation. This study revealed a significant association between the abundance of specific oral bacteria and dyslipidemia, suggesting the potential of using the oral microbiota as a biomarker for the early detection and management of dyslipidemia. Future research should explore the mechanisms through which oral bacteria influence lipid metabolism and the potential for microbioma-based therapies.

The immune system has long been recognized as a key driver in the progression of heart failure (HF). However, clinical trials targeting immune effectors have consistently failed to improve patient outcome across different HF aetiologies. The activation of the immune system in HF is complex, involving a broad network of pro-inflammatory and immune-modulating components, which complicates the identification of specific immune pathways suitable for therapeutic targeting. Increasing attention has been devoted to identifying gut microbial pathways that affect cardiac remodelling and metabolism and, thereby impacting the development of HF. In particular, gut microbiota-derived metabolites, absorbed by the host and transported to the peripheral circulation, can act as signalling molecules, influencing metabolism and immune homeostasis. Recent reports suggest that the gut microbiota plays a crucial role in modulating immune processes involved in HF. Here, we summarize recent advances in understanding the contributory role of gut microbiota in (auto-)immune pathways that critically determine the progression or alleviation of HF. We also thoroughly discuss potential gut microbiota-based intervention strategies to treat or decelerate HF progression.

Metabolism-disrupting agents (MDAs) are chemical, infectious or physical agents that increase the risk of metabolic disorders. Examples include pharmaceuticals, such as antidepressants, and environmental agents, such as bisphenol A. Various types of studies can provide evidence to identify MDAs, yet a systematic method is needed to integrate these data to help to identify such hazards. Inspired by work to improve hazard identification of carcinogens using key characteristics (KCs), we developed 12 KCs of MDAs based on our knowledge of processes underlying metabolic diseases and the effects of their causal agents: (1) alters function of the endocrine pancreas; (2) impairs function of adipose tissue; (3) alters nervous system control of metabolic function; (4) promotes insulin resistance; (5) disrupts metabolic signalling pathways; (6) alters development and fate of metabolic cell types; (7) alters energy homeostasis; (8) causes inappropriate nutrient handling and partitioning; (9) promotes chronic inflammation and immune dysregulation in metabolic tissues; (10) disrupts gastrointestinal tract function; (11) induces cellular stress pathways; and (12) disrupts circadian rhythms. In this Consensus Statement, we present the logic that revealed the KCs of MDAs and highlight evidence that supports the identification of KCs. We use chemical, infectious and physical agents as examples to illustrate how the KCs can be used to organize and use mechanistic data to help to identify MDAs.

The widespread commercialization of genetically modified (GM) crops makes it important to assess the potential impact of Bacillus thuringiensis (Bt) on non-target organisms. Pardosa astrigera is an important predator in agroforestry ecosystems, and female and male spiders may react differently to Bt toxins due to their different activity habits and nutritional requirements. In this study, we found that exposure to Cry2Aa protein did not affect the survival and body weight of P. astrigera during growth and development. However, according to 16S rRNA sequencing results of the P. astrigera adults, Cry2Aa protein not only changed the diversity of symbiont bacteria, but also changed its symbiont composition. During feeding on prey without Bt artificial feed, the dominant communities in female and male adults were Actinobacteria and Corynebacterium-1, respectively. Feeding on prey containing Cry2Aa protein, Firmicutes were the dominant phyla. At the genus level, Cry2Aa protein significantly increased the relative abundance of Enterococcus and became the dominant genus in females only. In addition, Bacillus, Weissella and other symbiotic bacteria had significant changes in females. In terms of species composition, sex differences resulted in the absence of different types of symbiotic bacteria. Functional analysis of enrichment pathways showed significant changes in various metabolic pathways such as "Carbohydrate metabolism" and "Nucleotide metabolism", and there are differences between the sexes. These findings provide new data information and support for revealing the different strategies of spiders to cope with Cry2Aa protein based on sex differences, and also provide new data information and support for environmental safety assessment of GM crops.

The gut microbiome changes with age and has been proposed to mediate the benefit of lifespan-extending interventions such as dietary restriction. However, the causes and consequences of microbiome ageing and the potential of such interventions remain unclear. Here we analysed 2,997 metagenomes collected longitudinally from 913 deeply phenotyped, genetically diverse mice to investigate interactions between the microbiome, ageing, dietary restriction (caloric restriction and fasting), host genetics and a range of health parameters. Among the numerous age-associated microbiome changes that we find in this cohort, increased microbiome uniqueness is the most consistent parameter across a second longitudinal mouse experiment that we performed on inbred mice and a compendium of 4,101 human metagenomes. Furthermore, cohousing experiments show that age-associated microbiome changes may be caused by an accumulation of stochastic environmental exposures (neutral theory) rather than by the influence of an ageing host (selection theory). Unexpectedly, the majority of taxonomic and functional microbiome features show small but significant heritability, and the amount of variation explained by host genetics is similar to ageing and dietary restriction. We also find that more intense dietary interventions lead to larger microbiome changes and that dietary restriction does not rejuvenate the microbiome. Lastly, we find that the microbiome is associated with multiple health parameters, including body composition, immune components and frailty, but not lifespan. Overall, this study sheds light on the factors influencing microbiome ageing and aspects of host physiology modulated by the microbiome.

The human microbiome, a complex ecosystem of microorganisms inhabiting the body, plays a critical role in human health. Investigating its association with host traits is essential for understanding its impact on various diseases. Although shotgun metagenomic sequencing technologies have produced vast amounts of microbiome data, analyzing such data is highly challenging due to its sparsity, noisiness, and high feature dimensionality. Here, we develop MIOSTONE, an accurate and interpretable neural network model for microbiome-disease association that simulates a real taxonomy by encoding the relationships among microbial features. The taxonomy-encoding architecture provides a natural bridge from variations in microbial taxa abundance to variations in traits, encompassing increasingly coarse scales from species to domains. MIOSTONE has the ability to determine whether taxa within the corresponding taxonomic group provide a better explanation in a data-driven manner. MIOSTONE serves as an effective predictive model, as it not only accurately predicts microbiome-trait associations across extensive simulated and real datasets but also offers interpretability for scientific discovery. Both attributes are crucial for facilitating in silico investigations into the biological mechanisms underlying such associations among microbial taxa. Video Abstract.

Kidney transplant recipients are prescribed an immunosuppressive therapy (IST) and some of them follow a high fat diet (HFD) despite medical recommendations. Both are frequently associated with gut microbiota changes and metabolic disorders. We aimed at precisely identifying the effect of the IST and the HFD on metabolic parameters and the gut microbiota in mice, and at establishing correlations between the latters.

8-week-old male mice were treated with IST (a combination of prednisone, mycophenolate mofetil and tacrolimus) or not and were fed HFD or standard chow. Metabolic parameters were measured, and the gut microbiota was explored by the quantification of specific bacterial groups by qPCR and by 16S rDNA sequencing.

The HFD increased insulinemia and decreased the fecal proportion of Bacteroidetes and of Bacteroides. The IST increased systolic blood pressure and the fecal proportion of Escherichia coli. The HFD and the IST administered together resulted in an additive effect on glucose intolerance, high fasting blood glucose, homeostasis model assessment of insulin resistance (HOMA-IR), percentage of fat mass, blood triglyceride, blood cholesterol, and endotoxemia. On the opposite, the HFD and the IST had antagonistic effects on body weight, the proportion of Firmicutes, the Firmicutes/Bacteroidetes ratio, and the proportion of Clostridium leptum, Bifidobacterium, and Lactobacillus in the feces. Finally, we found that the correlations between gut bacterial communities and metabolic consequences of the HFD were altered by the IST.

The IST and the HFD have specific consequences on the gut microbiota and metabolism. We hypothesize that the metabolic consequences are at least partially mediated by IST/HFD-induced dysbiosis.

The intestinal microbiome influences health and disease. Its composition is affected by host genetics and environmental exposures. Understanding host genetic effects is critical but challenging in humans, due to the difficulty of detecting, mapping and interpreting them. To address this, we analysed host genetic effects in four cohorts of outbred laboratory rats exposed to distinct but controlled environments. We found that polygenic host genetic effects were consistent across environments. We identified three replicated microbiome-associated loci. One involved a sialyltransferase gene and Paraprevotella and we found a similar association, between ST6GAL1 and Paraprevotella , in a human cohort. Given Paraprevotella 's known immunity-potentiating functions, this suggests ST6GAL1 's effects on IgA nephropathy and COVID-19 breakthrough infections may be mediated by Paraprevotella . Moreover, we found evidence of indirect genetic effects on microbiome phenotypes, which substantially increased their total genetic variance. Finally, we identified a novel mechanism whereby indirect genetic effects can contribute to "missing heritability".

The intestine is essential for digestion and nutrient absorption, and its altered function contributes to metabolic dysregulation and obesity-induced intestinal inflammation. Intestinal immune responses have been associated with the regulation of metabolic dysfunction during obesity. Given that the epithelial cell-derived cytokine IL-25 has been demonstrated to regulate metabolic disorders, we sought to examine the role of intestinal IL-25 in modulating a high-fat diet (HFD)-induced obesity. We found that mice on a high-fat diet exhibited decreased IL-25 expression in the small intestine. Intestinal IL-25 mRNA levels displayed an inverse association with plasma triglycerides, total cholesterol, glucose levels, and the expression of the cholesterol transporter Npc1l1 in the intestine. In HFD-induced obesity, transgenic mice overexpressing IL-25 in the intestinal epithelial cells demonstrated diminished mRNA expression of intestinal genes related to glucose, cholesterol, and fat absorption, along with chylomicron production, while also systemically decreasing plasma glucose, total cholesterol, and triglyceride levels, fat accumulation, and weight gain. In vitro, IL-25 treatment of human intestinal Caco-2 cells directly decreased cholesterol uptake and downregulated the expression of NPC1L1 and its transcriptional regulator, SREBP2. These findings highlight IL-25 as a potential modulator in the intestine that regulates intestinal cholesterol absorption and systemic metabolism in obesity.

Objective: Determine fermentable carbohydrates (FCs) consumption and health parameter differences between high and low FC consumers in US college students. Participants: Consented students (n = 571; 18-22 years) in a general nutrition course. Methods: Diet History Questionnaire quantified total FC plus subclasses, soluble dietary fibers (SDF), and polyols. Anthropometrics, blood pressure, and blood glucose were collected by standard measures. Median split classified FC intakes; multiple linear regression evaluated differences in health parameters between low and high FC consumers. Results: Average FC intakes for low and high FC consumers were 4.6 ± 1.4gand 10.9 ± 4.0g, with most coming from soluble dietary fibers. After controlling for confounders, low FCs showed higher diastolic blood pressure (β = 2.95, p = 0.04), blood glucose (β = 2.65 mg/dL; p = 0.02*), and BMI (β = 0.99, p = 0.050*, R2=0.04) than high consumers. Conclusions: Despite low intakes, these college students showed inverse associations between FC and diastolic blood pressure, blood glucose, and BMI. Long-term mechanistic studies are needed to evaluate potential relationships.

Over the last few decades, the prevalence of metabolic diseases such as obesity, diabetes, non-alcoholic fatty liver disease, hypertension, and hyperuricemia has surged, primarily due to high-fat diet (HFD). The pathologies of these metabolic diseases show disease-specific alterations in the composition and function of their gut microbiome. How HFD alters the microbiome and its metabolite to mediate adipose tissue (AT) inflammation and obesity is not well known. Thus, this study aimed to identify the changes in the gut microbiome and metabolomic signatures induced by an HFD to alter obesity. To explore the changes in the gut microbiota and metabolites, 16S rRNA gene amplicon sequencing and metabolomic analyses were performed after HFD and normal diet (ND) feeding. We noticed that, at taxonomic levels, the number of operational taxonomic units (OTUs), along with the Chao and Shannon indexes, significantly shifted in HFD-fed mice compared to those fed a ND. Similarly, at the phylum level, an increase in Firmicutes and a decrease in Bacteroidetes were noticed in HFD-fed mice. At the genus level, an increase in Lactobacillus and Ruminococcus was observed, while Allobaculum, Clostridium, and Akkermansia were markedly reduced in the HFD group. Many bacteria from the Ruminococcus genus impair bile acid metabolism and restrict weight loss. Firmicutes are efficient in breaking down complex carbohydrates into short-chain fatty acids (SCFAs) and other metabolites, whereas Bacteroidetes are involved in a more balanced or efficient energy extraction. Thus, an increase in Firmicutes over Bacteroidetes enhances the absorption of more calories from food, which may contribute to obesity. Taken together, the altered gut microbiota and metabolites trigger AT inflammation, which contributes to metabolic dysregulation and disease progression. Thus, this study highlights the potential of the gut microbiome in the development of therapeutic strategies for obesity and related metabolic disorders.

Obesity is positively associated with colorectal cancer (CRC) risk. Diet not only contributes to obesity, but also strongly influences the gut microbiota, a factor that is thought to independently affect CRC. To isolate the role of obesity-associated gut microbiota in CRC and to assess the impact of diet composition on this relationship, we transplanted the gut microbiota from donor mice that developed obesity or remained lean on a high-fat diet (HFD), Western diet (WD), or low-fat diet (LFD) into antibiotic-treated recipient mice that subsequently received azoxymethane to induce CRC. We hypothesized that the obesogenic diets of the donor mice, rather than their obesity status, would be a stronger driver of gut microbiota-mediated CRC development. Interestingly, while evidence supporting our hypothesis was observed, differential effects on CRC outcomes based on the type of obesogenic diets were found, such that HFD-associated gut microbiota promotes tumor incidence whereas WD-associated gut microbiota promotes tumor growth. Significantly enriched bacterial taxa present before tumor induction may be mediating these results through intestinal permeability or inflammation, such as Sutterella and Dorea in mice received HFD-associated gut microbiota, and Bacteroidetes in mice received WD-microbiota. Overall, our results demonstrated that diet drives the gut microbiota-derived impact on CRC development.

Psoriasis is an inflammatory disease linked to gut microbiome dysbiosis. However, the mechanisms underlying gut microbiome changes caused by dietary habits in psoriasis remain unclear.

We performed a case-control study including 64 psoriasis patients and 64 age-, sex-, and body mass index (BMI)-matched controls. Stool samples were collected for metagenomics sequencing. The differential abundance analysis was performed to identify differentially abundant taxa between psoriasis and control groups. The dietary intake frequency information of each included subject was obtained through face-to-face interviews. Mediation analysis was used to identify potential mediators of the gut microbiome alterations in psoriasis.

The gut microbiome of psoriasis patients was significantly alterated when compared to controls. Anaerostipes Hadrus, Blautia Wexlerae, and the other six species may be beneficial to psoriasis. However, Prevotella Copri and Eggerthellaceae could be pathogenic bacteria. The study also identified correlations between specific dietary habits and psoriasis, with the largest correlation observed between poultry consumption and psoriasis (OR=0.735, P=0.001), followed by red meat (OR=0.784, P=0.007) and fresh vegetables (OR=0.794, P=0.028). Mediation analysis revealed that Anaerostipes hadrus, Dorea longicatena, and Eggerthella lenta mediated the association between poultry and psoriasis.

The characteristics of intestinal flora in psoriasis patients were significantly different from controls. Intestinal flora mediated the association between diet and psoriasis to some extent. This study provides new insights for adjuvant treatments of psoriasis through dietary and intestinal microbiota interventions.

This study aimed to compare oral microbiome profiles between obese and lean individuals without clinical periodontitis, and to assess changes in the oral microbiome of obese subjects following bariatric surgery.

Individuals with a body mass index (BMI) > 30 were enrolled in the obese group, whereas those with a BMI < 23 served as controls. The obese surgery group, which consented to bariatric surgery, was followed up at 1, 3, and 6 months with clinical examinations. Oral examinations were conducted and periodontal disease was classified based on probing results. Saliva, buccal and subgingival microbiome samples were analyzed for community diversity, relative bacterial abundance, and differential abundance between control (n = 24) and obese group (n = 31). To evaluate effect size and statistical power, we used micropower, a simulation-based method for Permutational Multivariate Analysis of Variance-based β-diversity comparisons.

The obese group exhibited distinct alpha diversity (buccal: Chao1 p = 0.0002, Shannon p = 0.0003, supragingival: Shannon p < 0.0001) compared with the control group. Bray-Curtis distance analysis indicated significant disparities in microbiome composition distribution in saliva (p = 0.003), buccal (p = 0.002), and subgingival plaque samples (p = 0.001). Although the obese and normal weight groups exhibited no significant periodontal differences, the obese group showed distinct species associated with periodontal disease, especially in subgingival plaque including Filifactor alocis, Peptostreptococcaceae spp., Prevotella spp., and Treponema maltophilum. Cluster analysis of the obese surgery group indicated the emergence of microbiomes associated with a healthy state that increased over time including Streptococcus salivarious and various Veillonella spp., whereas clusters containing periodontal pathogens including Porphyromonas spp., tended to diminish.

The oral microbiome at 6 months post-bariatric surgery indicates a potential shift toward a healthy periodontal state, suggesting that weight loss interventions may positively impact oral microbial communities even in the absence of clinical periodontitis.

Pancreatic cancer, one of the most lethal malignancies, remains challenging due to late diagnosis, aggressive progression, and therapeutic resistance. Recent advances have revealed the presence of intratumoral microbiota, predominantly originating from the oral and gut microbiomes, which play pivotal roles in pancreatic cancer pathogenesis. The dynamic interplay between oral and gut microbial communities, termed the "oral-gut microbiota axis," contributes multifacetedly to pancreatic ductal adenocarcinoma (PDAC). Microbial translocation via anatomical or circulatory routes establishes tumor-resident microbiota, driving oncogenesis through metabolic reprogramming, immune regulation, inhibition of apoptosis, chronic inflammation, and dysregulation of the cell cycle. Additionally, intratumoral microbiota promote chemoresistance and immune evasion, further complicating treatment outcomes. Emerging evidence highlights microbial signatures in saliva and fecal samples as promising non-invasive diagnostic biomarkers, while microbial diversity correlates with prognosis. Therapeutic strategies targeting this axis-such as antibiotics, probiotics, and engineered bacteria-demonstrate potential to enhance treatment efficacy. By integrating mechanisms of microbial influence on tumor biology, drug resistance, and therapeutic applications, the oral-gut microbiota axis emerges as a critical regulator of PDAC, offering novel perspectives for early detection, prognostic assessment, and microbiome-based therapeutic interventions.

Polysaccharides are one of the primary active components of Radix Hedysari, although their regulatory effects on gut microbiota remain poorly understood. In this study, Radix Hedysari polysaccharides (RHPS) were isolated and purified, yielding three fractions: RHPS-1, RHPS-2, and RHPS-4. The yields of these fractions were 51.33 %, 3.15 %, and 2.34 %, respectively, with weight-average molecular weights of 18.781, 25.660, and 100.149 kDa. The three polysaccharides were composed of arabinose, galactose, glucose, glucuronic acid. RHPS-1 exhibits good antioxidant, antibacterial, and immune-enhancing activities. Further purification of RHPS-1 yielded RHPS-1-1, and it was found that RHPS-1-1 enhances the growth of beneficial bacteria while suppressing the growth of harmful bacteria in mice. Additionally, mice treated with RHPS-1-1 were primarily involved in bile acid, short-chain fatty acid, and energy metabolism pathways. Our results represent the first demonstration that RHPS-1-1 exhibits good biological activity and possesses the ability to regulate the gut microbiota and its metabolites in mice.

Diversity of the gut microbiota has proven to be related with host physiology, health and behavior, influencing host ecology and evolution. Gut microbial community relationships often recapitulate primate phylogeny, suggesting phylosymbiotic associations. Howler monkeys (Alouatta) have been a model for the study of host-gut microbiota relationships, showing the influence of different host related and environmental factors. Differences in life-history traits and feeding behavior with other atelids, like spider monkeys, may reveal distinct patterns of bacterial gut communities, yet few wild populations have been studied; likewise, gut microbiota studies of hybrid populations are mostly lacking. We analyzed diversity and abundance patterns of the gut microbiota of wild populations of the three Mexican primates Ateles geoffroyi, Alouatta palliata and A. pigra from different regions across its distribution in the country, including sympatric localities and the Alouatta hybrid zone. Interspecific differences in gut microbial diversity were higher than intraspecific differences, concordant with phylosymbiosis. Ateles harbored the more differentiated diversity with a major presence of rare taxa, while differences were less strong between Alouatta species. Hybrids had a microbial diversity in-between their parental species, yet also showing unique microbe taxa. Genetic distances between Alouatta individuals correlated positively with their gut microbial dissimilarities. Results show that interspecific and intraspecific overall diversity, abundance and composition patterns are affected by environment, geographic distribution and host genetics. Our study provides the first comprehensive study of gut microbiota of the three Mexican primates and hybrid populations.

Obesity, a pressing global health issue, is intricately associated with distinct gut microbiota profiles. Bariatric surgeries, such as Laparoscopic Sleeve Gastrectomy (LSG), Sleeve Gastrectomy (SG), and Roux-en-Y Gastric Bypass (RYGB), induce substantial weight loss and reshape gut microbiota composition and functionality, yet their comparative impacts remain underexplored.

This study integrated four published metagenomic datasets, encompassing 500 samples, and employed a unified bioinformatics workflow for analysis. We assessed gut microbiota α-diversity, identified species biomarkers using three differential analysis approaches, and constructed high-quality Metagenome-Assembled Genomes (MAGs). Comparative genomic, functional profiling and KEGG pathway analyses were performed, alongside estimation of microbial growth rates via Peak-to-Trough Ratios (PTRs).

RYGB exhibited the most pronounced enhancement of gut microbiota α-diversity compared to LSG and SG. Cross-cohort analysis identified 39 species biomarkers: 27 enriched in the non-obesity group (NonOB_Enrich) and 12 in the obesity group (OB_Enrich). Among the MAGs, 177 were NonOB_Enrich and 14 were OB_Enrich. NonOB_Enrich MAGs displayed enriched carbohydrate degradation profiles (e.g., GH105, GH2, GH23, GH43, and GT0 families) and higher gene diversity in fatty acid biosynthesis and secondary metabolite pathways, alongside significant enrichment in amino acid metabolism (KEGG analysis). Post-surgery, Akkermansia muciniphila and Bacteroides uniformis showed elevated growth rates based on PTRs.

These findings underscore RYGB's superior impact on gut microbiota diversity and highlight distinct microbial functional adaptations linked to weight loss, offering insights for targeted therapeutic strategies.

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.

Obesity affects millions of people in the world. The gut microbiome influences body fat accumulation, but the mechanisms remain to be investigated. Here, we show an association between microbial aromatic amino acid metabolites in serum and body fat accumulation in a large Chinese longitudinal cohort. We next identify that 4-hydroxyphenylacetic acid (4HPAA) and its analogues effectively protect male mice from high-fat-diet-induced obesity. These metabolites act on intestinal mucosa to regulate the immune response and control lipid uptake, which protects against obesity. We further demonstrate that T cells and B cells are not vital for 4HPAA-mediated obesity prevention, and innate lymphoid cells have antagonistic roles. Together, these findings reveal specific microbial metabolites as pivotal molecules to prohibit obesity through immune control, establishing mechanisms of host modulation by gut microbial metabolites.

Toll-like receptor 5 (TLR5), integral to the immune system as a primary sensor for flagellin, is central to the link between innate and adaptive immunity, modulating immune responses and cytokine production essential for defense against flagellated pathogens and immune tolerance. This review consolidates the understanding of TLR5's structural and signaling mechanisms and its interactions with flagellin, shedding light on its dual role in immune responses and its promise as a therapeutic target. It highlights TLR5's intricate role in the pathogenesis of obesity-related hypertension, a growing global health concern that correlates with rising obesity rates and is characterized by a complex interplay of immune responses and metabolic dysregulation. Despite the current understanding, the impact of TLR5 on obesity-related hypertension is marked by conflicting findings, indicating a need for further exploration. The review critically analyzes the existing literature, providing novel insights from rodent models and human studies that underscore TLR5's therapeutic potential, setting the stage for transformative research in managing obesity-related hypertension. It calls for deeper investigation into TLR5's multifaceted role, emphasizing its promise as a target for managing obesity-related hypertension and the necessity for future research to clarify its complexities and to innovate treatment strategies.

Foodborne bacterial diarrhea involves complex pathogen-microbiota-host interactions. Pathogen-displacing probiotics are increasingly popular, but heterogeneous patient outcomes highlighted the need to understand individualized host-probiotic activity. Using the mouse gut commensal Escherichia coli 8178 and the human probiotic E. coli Nissle 1917, we found that the degree of protection against the enteric pathogen Salmonella enterica serovar Typhimurium (S. Tm) varies across mice with distinct gut microbiotas. Pathogen clearance is linked to enteropathy severity and subsequent recruitment of intraluminal neutrophils, which differs in a microbiota-dependent manner. By combining mouse knockout and antibody-mediated depletion models with bacterial genetics, we show that neutrophils and host-derived reactive oxygen species directly influence E. coli-mediated S. Tm displacement by potentiating siderophore-bound toxin killing. Our work demonstrates how host immune factors shape pathogen-displacing probiotic efficiency while also revealing an unconventional antagonistic interaction where a gut commensal and the host synergize to displace an enteric pathogen.

Gut microbial dysbiosis, or altered gut microbial communities, in Alzheimer's Disease suggests a pathogenic role for gut inflammation and microbial products in shaping a neuroinflammatory environment. Similarly, metabolic diseases, such as obesity and diabetes, are also associated with an increased risk of Alzheimer's Disease. As the metabolic landscape shifts during gut inflammation, and gut inflammation in turn impacts metabolic processes, we explore how these interconnected pathways may contribute to the progression of Alzheimer's Disease. Additionally, we discuss the role of bacterial amyloids produced by gut microbes, which may exacerbate amyloid aggregation in the brain and contribute to neurodegenerative processes. Furthermore, we highlight potential therapeutic strategies aimed at reducing gut inflammation, improving metabolic health, and decreasing amyloid content as a means to mitigate Alzheimer's Disease progression. These approaches, targeting the gut-brain-metabolic axis, could offer promising avenues for delaying or preventing cognitive decline in affected individuals.

Metabolic diseases, such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease, have emerged as major global health challenges. Recent research has revealed that the gut microbiome is closely associated with the development of these conditions. The Food and Drug Administration has recognized certain probiotic strains with therapeutic potential, classifying them as live biotherapeutic products (LBPs). LBPs, which are derived from naturally occurring microorganisms, may present an effective strategy for treating metabolic diseases by restoring gut microbiota balance and regulating metabolic functions. This review explores the development of LBPs specifically for metabolic disease treatments, covering every phase from strain identification, non-clinical and clinical trials, manufacturing and formulation to regulatory approval. Furthermore, it addresses the challenges involved in the commercialization of these therapies. By offering critical insights into the research and development of LBPs for metabolic disease treatment, this review aims to contribute to the progress of these promising therapies.

Obesity is a major global concern and is generally attributed to a combination of genetic and environmental factors. Several hypotheses have been proposed to explain the evolutionary origins of obesity epidemic, including thrifty and drifty genotypes, and changes in thermogenesis. Here, we put forward the hypothesis of metaflammation, which proposes that due to intense selection pressures exerted by environmental pathogens, specific genes that help develop a robust defense mechanism against infectious diseases have had evolutionary advantages and that this may contribute to obesity in modern times due to connections between the immune and energy storage systems. Indeed, incorporating the genetic variations of gut microbiota into the complex genetic framework of obesity makes it more polygenic than previously believed. Thus, uncovering the evolutionary origins of obesity requires a multifaceted approach that considers the complexity of human history, the unique genetic makeup of different populations, and the influence of gut microbiome on host genetics.

Recent research on the gut-brain axis has deepened our understanding of the correlation between gut bacteria and the neurological system. The inflammatory response triggered by gut microbiota may be associated with neurodegenerative diseases. Additionally, the impact of gut microbiota on emotional state, known as the "Gut-mood" relationship, could play a role in depression and anxiety disorders.

This review summarizes recent data on the role of gut-brain axis in the pathophysiology of neuropsychiatric and neurological disorders including epilepsy, schizophrenia, Alzheimer's disease, brain cancer, Parkinson's disease, bipolar disorder and stroke. Also, we conducted a Mendelian randomization study on seven neurological disorders (Epilepsy, schizophrenia, Alzheimer's disease, brain cancer, Parkinson's disease, bipolar disorder and stroke). MR-Egger and MR-PRESSO tests confirmed the robustness of analysis against horizontal pleiotropy.

By comparing the protective and risk factors for neurological disorders found in our research and other researches, we can furtherly determine valuable indicators for disease evolution tracking and potential treatment targets. Future research should explore extensive microbiome genome-wide association study datasets using metagenomics sequencing techniques to deepen our understanding of connections and causality between neurological disorders.

Barley sprouts, the germinated and grown leaves of barley, contain various bioactive compounds, including policosanol, saponarin, and lutonarin. The ingestion of barley sprouts may benefit canine weight management, potentially owing to the anti-obesity properties of bioactive compounds. However, there is limited evidence on the efficacy and safety of barley sprout supplementation in dogs. Therefore, through this study, we assessed the impact of barley-sprout-supplemented diet on body weight and health markers in healthy adult beagles over a 16-week period. The results showed a 7.2% reduction in body weight in dogs fed the barley sprout diet. Hematology, complete blood cell count, and blood biochemistry analyses confirmed that all parameters remained within normal ranges, with no significant differences observed between the control and experimental groups. Although the levels of IFN-γ, IL-6, and insulin remained stable, leptin, a hormone associated with body fat, significantly decreased. Further analysis of alterations in the gut microbiota following barley sprout supplementation revealed no significant differences between the control and experimental groups with respect to alpha and beta diversity analysis. The shift at the phylum level, with a decrease in Firmicutes and an increase in Bacteroidetes, resulted in a reduced Firmicutes/Bacteroidetes ratio. Additionally, the abundance of the Ruminococcus gnavus group was high in the experimental group. Functional predictions indicated an enhancement in carbohydrate, amino acid, and cofactor and vitamin metabolism. These findings suggest that a barley sprouts diet is safe for dogs and may offer benefits for weight management through favorable alterations in body weight, hormone levels, and gut microbiota composition.

We investigated the relationship between nut and legume intake and risk of Crohn's disease (CD) and ulcerative colitis (UC).

We conducted a prospective cohort study of 223 283 adults from the Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (1986-2017), excluding those with inflammatory bowel disease (IBD) at baseline. Food frequency questionnaires were used to calculate nut and legume intake. Inflammatory bowel disease was self-reported on questionnaires and confirmed via blinded record review. Using Cox proportional hazards models, we calculated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CD and UC according to categories of nut and legume intake.

In over 5 460 315 person-years of follow-up (CD = 371, UC = 481), neither nut nor legume intake was associated with CD or UC risk. Compared to those who never consumed nuts, those who consumed nuts ≥2 times/week had an aHR = 0.96 (95% CI, 0.63-1.47; Ptrend = 0.57) for CD and 1.30 (95% CI, 0.92-1.84; Ptrend = 0.36) for UC. Compared to those who consumed legumes 0-3 times/month, those who consumed legumes ≥4 times/week had an aHR of 1.26 (95% CI, 0.78-2.04; Ptrend = 0.59) for CD and 0.72 (95% CI, 0.44-1.18; Ptrend = 0.20) for UC. Baseline BMI modified the relationship between nut intake and CD risk (Pint = 0.03). In those with BMI ≥25, the aHR for CD was 0.14 (95% CI, 0.03-0.56; P = .006) per additional serving/day of nuts compared with 0.88 (95% CI, 0.45-1.74; P = .72) for those with BMI <25.

Nut and legume intake were not associated with CD or UC risk. However, higher nut intake decreased CD risk in overweight or obese individuals. Thus, personalized-risk stratification, rather than generalized dietary recommendations, may be important for IBD prevention strategies.

Akkermansia muciniphila is a promising target for managing obesity and type 2 diabetes (T2D), but human studies are limited. We conducted a 12-week randomized, double-blind, placebo-controlled trial involving 58 participants with overweight or obese T2D, who received A. muciniphila (AKK-WST01) or placebo, along with routine lifestyle guidance. Both groups showed decreases in body weight and glycated hemoglobin (HbA1c), without significant between-group differences. In participants with low baseline A. muciniphila, AKK-WST01 supplementation showed high colonization efficiency and significant reductions in body weight, fat mass, and HbA1c, which were not found in the placebo group. However, AKK-WST01 supplementation showed poor colonization and no significant clinical improvements in participants with high baseline A. muciniphila. These findings were verified in germ-free mice receiving feces with low or high A. muciniphila. Our study indicates that metabolic benefits of A. muciniphila supplementation could depend on its baseline intestinal levels, supporting the potential for gut microbiota-guided probiotic supplementation. (ClinicalTrials.gov number, NCT04797442).