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 role of xenobiotic disruption of microbiota, corresponding dysbiosis, and potential links to host metabolic diseases are of critical importance. In this study, we used a widely prescribed antipsychotic drug, risperidone, known to influence weight gain in humans, to induce weight gain in C57BL/6J female mice. We hypothesized that microbes essential for maintaining gut homeostasis and energy balance would be depleted following treatment with risperidone, leading to enhanced weight gain relative to controls. Thus, we performed metagenomic analyses on stool samples to identify microbes that were excluded in risperidone-treated animals but remained present in controls. We identified multiple taxa including Limosilactobacillus reuteri as a candidate for further study. Oral supplementation with L. reuteri protected against risperidone-induced weight gain (RIWG) and was dependent on cellular production of a specialized metabolite, reutericyclin. Further, synthetic reutericyclin was sufficient to mitigate RIWG. Both synthetic reutericyclin and L. reuteri restored energy balance in the presence of risperidone to mitigate excess weight gain and induce shifts in the microbiome associated with leanness. In total, our results identify reutericyclin production by L. reuteri as a potential probiotic to restore energy balance induced by risperidone and to promote leanness.

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.

Excessive intake of dietary fats is strongly associated with an increased risk of various chronic diseases, such as obesity, diabetes, hepatic metabolic disorders, cardiovascular disease, chronic intestinal inflammation, and certain cancers. A significant portion of the adverse effects of high-fat diet on disease risk is mediated through modifications in the gut microbiota. Specifically, high-fat diets are linked to reduced microbial diversity, an overgrowth of gram-negative bacteria, an elevated Firmicutes-to-Bacteroidetes ratio, and alterations at various taxonomic levels. These microbial alterations influence the intestinal metabolism of small molecules, which subsequently increases intestinal permeability, exacerbates inflammatory responses, disrupts metabolic functions, and impairs signal transduction pathways in the host. Consequently, diet-induced changes in the gut microbiota play a crucial role in the initiation and progression of chronic diseases. This review explores the relationship between high-fat diets and gut microbiota, highlighting their roles and underlying mechanisms in the development of chronic metabolic diseases. Additionally, we propose probiotic interventions may serve as a promising adjunctive therapy to counteract the negative effects of high-fat diet-induced alterations in gut microbiota composition.

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.

Dysbiosis refers to the disruption of the gut microbiota balance and is the pathological basis of various diseases. The main pathogenic mechanisms include impaired intestinal mucosal barrier function, inflammation activation, immune dysregulation, and metabolic abnormalities. These mechanisms involve dysfunctions in the gut-brain axis, gut-liver axis, and others to cause broader effects. Although the association between diseases caused by dysbiosis has been extensively studied, many questions remain regarding the specific pathogenic mechanisms and treatment strategies. This review begins by examining the causes of gut microbiota dysbiosis and summarizes the potential mechanisms of representative diseases caused by microbiota imbalance. It integrates clinical evidence to explore preventive and therapeutic strategies targeting gut microbiota dysregulation, emphasizing the importance of understanding gut microbiota dysbiosis. Finally, we summarized the development of artificial intelligence (AI) in the gut microbiota research and suggested that it will play a critical role in future studies on gut dysbiosis. The research combining multiomics technologies and AI will further uncover the complex mechanisms of gut microbiota dysbiosis. It will drive the development of personalized treatment strategies.

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.

Obesity is recognized as a global epidemic that can result in changes in the human body and metabolism. Accumulating evidence indicates that gut microbiota (GM) can affect the development of obesity. The GM not only plays a crucial role in digesting and absorbing nutrients, but also in maintaining the overall health of the host. Dietary supplements such as non-starch polysaccharides are mainly fermented by the GM in the colon. Recent findings suggest that shaping the GM through the prebiotic function of non-starch polysaccharides may be a viable strategy against obesity. In this paper, the effects of non-starch polysaccharides on host health, together with their prebiotic function influencing the GM to control obesity via the gut-target organ axis, are reviewed. Potential perspectives of non-starch polysaccharides exhibiting anti-obesity effects via the gut-target organ axis are proposed for future research.

Gut microbiota plays crucial roles in host metabolism, diseases and development. It has also been reported to be associated with growth performance in pigs. However, the bacterial species influencing pig growth performance have not been isolated, and the mechanisms remain unclear.

In this study, we collected 500 gut microbial samples from two Chinese indigenous pig breeds, including 244 fecal samples from Bamaxiang (BMX) pigs and 256 cecum content samples from Erhualian (EHL) pigs, to investigate the relationship between gut microbiota and pig growth traits. Bacterial compositions were determined by 16 S rRNA gene sequencing, and association analysis was performed using a two-part model. We found that the Firmicutes-to-Bacteroidota ratio in fecal samples from BMX pigs was negatively associated with average daily gain (P = 0.0085). Amplicon sequence variants (ASVs) belonging to Prevotella and three ASVs annotated to Oscillospiraceae were negatively associated with pig growth traits, while ASVs annotated to Muribaculaceae and Rikenellaceae showed positive correlations with growth traits in BMX fecal samples. In cecum content samples from EHL pigs, ASVs belonging to Prevotella, Lactobacillus delbrueckii, and Lachnospiraceae were negatively associated with growth performance, whereas one ASV belonging to Rikenellaceae demonstrated a positive association. Predicted functional capacity analysis revealed that metabolic pathways related to the digestive system, glycan biosynthesis and metabolism, signaling molecules and interactions, and xenobiotics biodegradation and metabolism were positively associated with pig growth traits. Conversely, the excretory system pathway showed a negative correlation. These pathways were found to correlate with growth trait-associated bacterial ASVs, suggesting that alterations in gut bacterial composition led to functional capacity shifts in the gut microbiome, subsequently affecting porcine growth.

Our results gave significant insights about the effect of gut microbiota on pig growth and provided important evidence to support further isolation of bacterial taxa that influence pig growth for elucidating their mechanisms.

SUMMARYRecent advances in therapeutic probiotics have shown promising results across various health conditions, reflecting a growing understanding of the human microbiome's role in health and disease. However, comprehensive reviews integrating the diverse therapeutic effects of probiotics in human subjects have been limited. By analyzing randomized controlled trials (RCTs) and meta-analyses, this review provides a comprehensive overview of key developments in probiotic interventions targeting gut, liver, skin, vaginal, mental, and oral health. Emerging evidence supports the efficacy of specific probiotic strains and combinations in treating a wide range of disorders, from gastrointestinal (GI) and liver diseases to dermatological conditions, bacterial vaginosis, mental disorders, and oral diseases. We discuss the expanding understanding of microbiome-organ connections underlying probiotic mechanisms of action. While many clinical trials demonstrate significant benefits, we acknowledge areas requiring further large-scale studies to establish definitive efficacy and optimal treatment protocols. The review addresses challenges in standardizing probiotic research methodologies and emphasizes the importance of considering individual variations in microbiome composition and host genetics. Additionally, we explore emerging concepts such as the oral-gut-brain axis and future directions, including high-resolution microbiome profiling, host-microbe interaction studies, organoid models, and artificial intelligence applications in probiotic research. Overall, this review offers a comprehensive update on the current state of therapeutic probiotics across multiple domains of human health, providing insights into future directions and the potential for probiotics to revolutionize preventive and therapeutic medicine.

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 microbiomes contribute to animal health and fitness. The immense biochemical diversity of bacteria holds particular potential for neutralizing environmental toxins and thus helping hosts deal with new toxic challenges. To explore this potential, we used Caenorhabditis elegans harboring a defined microbiome, and the antibiotic neomycin as a model toxin, differentially affecting microbiome strains, and also toxic to worms. Worms exposed to neomycin showed delayed development and reduced survival but were protected when colonized with neomycin-resistant Stenotrophomonas. 16S rRNA sequencing, bacterial load quantification, genetic manipulation, and behavioral assays showed that protection was linked to enrichment of Stenotrophomonas carrying a neomycin-modifying enzyme. Enrichment was facilitated by altered bacterial competition in the gut, as well as by KGB-1/JNK-dependent behavioral changes. While microbiome remodeling conferred toxin resistance, it was associated with reduced infection resistance and metabolic changes. These findings suggest that microbiome adaptation can help animals cope with stressors but may have long-term consequences that add to effects of direct intoxication.

Microplastics (MPs) negatively impact various terrestrial animals, but their comprehensive effects on Gallus gallus domesticus, key agricultural and ecological species connecting people and the environment, are not well-documented. This study investigates the effects of polyethylene (PE) MPs and phthalate esters (PAEs) on chicken growth, liver metabolism, and gut microbiota using multi-omics and 16S rRNA sequencing technology. Results show that PE MPs, particularly those containing PAEs, significantly reduced body weight gain and hepatic triglyceride levels by up to 71.2 % and 50.1 %, respectively (p < 0.05). The clean MPs affected energy metabolism, while PAE-spiked MPs disrupted fatty acid metabolism and triggered immune and inflammatory responses in the liver. Key genes related to fatty acid metabolism such as FAN, SCD and ELOVL5 were significantly downregulated, leading to imbalances in lipid metabolism. These disruptions in PAE-spiked MPs exposure were associated with the altered gut microbiota balance, including increased Firmicutes/Bacteroidetes ratios and changes in Actinobacteriota and Proteobacteria abundance. Totally, the study highlights a "Trojan Horse" effect, where MPs act as carriers for PAEs, intensifying toxicity through gut-liver axis interactions. The findings emphasize the role of gut microbiota in mediating liver dysfunction and impaired growth.

Breakthroughs in metabolomics technology have revealed the direct regulatory role of metabolites in physiology and disease. Recent data have highlighted the bioactive metabolites involved in the etiology and prevention, and treatment of metabolic diseases such as obesity, nonalcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM), and atherosclerosis. Numerous studies reveal that endogenous metabolites biosynthesized by host organisms or gut microflora regulate metabolic responses and disorders. Lipids, amino acids, and bile acids (BAs), as endogenous metabolic modulators, regulate energy metabolism, insulin sensitivity, and immune response through multiple pathways, such as insulin signaling cascade, chemical modifications, and metabolite-macromolecule interactions. Furthermore, the gut microbial metabolites short-chain fatty acids (SCFAs), as signaling regulators have a variety of beneficial impacts in regulating energy metabolic homeostasis. In this review, we will summarize information about the roles of bioactive metabolites in the pathogenesis of many metabolic diseases. Furthermore, we discuss the potential value of metabolites in the promising preventive and therapeutic perspectives of human metabolic diseases.

The field of precision nutrition aims to develop dietary approaches based on individual biological factors such as genomics or the gut microbiota. The gut microbiota, which is the highly individualized and complex community of microbes residing in the colon, is a key contributor to human physiology. Although gut microbes play multiple roles in the metabolism of nutrients, their role in modulating the absorption of dietary energy from foods that escape digestion in the small intestine has the potential to variably affect energy balance and, thus, body weight. The fate of this energy, and its subsequent impact on body weight, is well described in rodents and is emerging in humans. This narrative review is focused on recent clinical evidence of the role of the gut microbiota in human energy balance, specifically its impact on energy available to the human host. Despite recent progress, remaining gaps in knowledge present opportunities for developing and implementing strategies to understand causal microbial mechanisms related to energy balance. We propose that implementing rigorous microbiota-focused measurements in the context of innovative clinical trial designs will elucidate integrated diet-host-gut microbiota mechanisms. These mechanisms are primed to be targets for precision nutrition interventions to optimize energy balance to achieve desired weight outcomes. Given the magnitude and impact of the obesity epidemic, implementing these interventions within comprehensive weight management paradigms has the potential to be of public health significance.

The gut microbiota has been implicated in adult obesity, but the causality is still unclear. It has been hypothesized that an obesity-prone gut microbiota can be established in infancy, but only few studies have examined the early-life gut microbiota in relation to obesity in childhood, and no consistent associations have been reported. Here, we examine the association between the early-life gut microbiota and body mass index (BMI) development and body composition throughout childhood.

Gut microbiota from stool were collected from 700 children in the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort at ages of 1 week, 1month, 1 year, 4 years, and 6 years and analyzed by 16S rRNA gene sequencing. Outcomes included BMI World Health Organization (WHO) Z scores (zBMI), overweight (zBMI > 1.04) and obesity (zBMI > 1.64) (0-10 years), and adiposity rebound and body composition from dual-energy X-ray absorptiometry at 6 years.

The early-life gut microbiota diversity, overall composition, and individual taxon abundances in unsupervised and supervised models were not consistently associated with either current or later BMI Z scores, overweight, obesity, adiposity rebound, or body composition in childhood.

In a deeply characterized longitudinal birth cohort, we did not observe any consistent associations between the early-life gut microbiota and BMI or risk of obesity in later childhood. While this does not conclusively rule out a relationship, it suggests that if such associations exist, they may be more complex and potentially influenced by factors emerging later in life, including lifestyle changes.

COPSAC is funded by private and public research funds (all listed on www.copsac.com).

Early-life antibiotic (ELA) exposure has garnered attention for its potential role in modulating obesity risk, although outcomes from mouse experiments and human epidemiological studies often vary based on dosage and sex. Low-dose (subtherapeutic) antibiotics can enhance energy availability through moderate alterations in gut microbiome profile, while high-dose (therapeutic) antibiotics substantially deplete the gut microbiota, thereby contributing to short-term negative energy balance. In this perspective, we propose a framework to understand how these distinct impacts of antibiotics on the gut microbiome during critical developmental windows shape long-term obesity risk through their influence on host energy balance. Using this framework, we then propose several hypotheses to explain variation in ELA-induced obesity outcomes across males and females. We conclude by discussing the evolutionary implications of ELAs, positing that the response of the gut microbiome to ELAs may signal energy availability and environmental volatility, influencing metabolic programming and adaptive traits across generations.

Dietary fat composition has changed substantially during the obesity epidemic. As adipocyte hyperplasia is a major mechanism of adipose expansion, we aim to ascertain how dietary fats affect adipogenesis during obesity. We employ an unbiased dietary screen to identify oleic acid (OA) as the only dietary fatty acid that induces obesogenic hyperplasia at physiologic levels and show that plasma monounsaturated fatty acids (MUFAs), which are mostly OA, are associated with human obesity. OA stimulates adipogenesis in mouse and human adipocyte precursor cells (APCs) by increasing AKT2 signaling, a hallmark of obesogenic hyperplasia, and reducing LXR activity. High OA consumption decreases LXRα Ser196 phosphorylation in APCs, while blocking LXRα phosphorylation results in APC hyperproliferation. As OA is increasingly being incorporated into dietary fats due to purported health benefits, our finding that OA is a unique physiologic regulator of adipose biology underscores the importance of understanding how high OA consumption affects metabolic health.

The pathogenesis of non-organic anorexia in children is not clear. This study intends to analyze intestinal bacteria to provide a relevant theoretical basis for the clinical rational selection of microecological agents. In the present study, children with non-organic anorexia were included in the anorexia group and normal healthy children in the control group. Stool samples were collected for the bioinformatics analysis after PCR and high-throughput sequencing. The results showed that the Ace, Chao, and Shannon indexes in the anorexia group were higher than those in the control group, while the Simpson index in the control group was lower than in the anorexia group. There were 14 taxa in the anorexia group and 11 taxa in the healthy control group at the phylum level, and 193 taxa in the anorexia group and 180 in the control group at the genus level. The dominant bacteria at the phylum level of the two groups were the same, while there were 16 dominant bacteria taxa in the anorexia group and 17 in the control group at the genus level. The ratio of percentage abundance of Bacteroidetes to that of Firmicutes (the B/F index) in the anorexia group was higher than in the control group. The abundance of Bacteroidetes in the anorexia group was higher than that in the control group, and the abundance of Actinomycetes in the control group was higher than that in the anorexia group. There were significant differences in 14 dominant genera between the two groups at the genus classification level. The LEfSe multilevel species difference analysis showed that at the phylum level, the significant influential bacterial taxa in the anorexia group were Bacteroidetes and Actinobacteria in the control group. At the genus level, the significant influential bacterial taxa in the anorexia group were Bacteroides, Faecalibacterium, and Subdoligranulum, and Bifidobacterium, Blautia, Streptococcus, Lachnoclostridium, and Erysipelatoclostridium in the control group. We conclude that the increase in Bacteroides abundance or in the B/F index and the reduction in Bifidobacterium abundance were related to the pathogenesis of anorexia.

This study aimed to investigate the effects of Boletus edulis Bull: Fr. polysaccharide (BEP), extracted using a deep eutectic solvent based on l-lactic acid and glycine, on glucose and lipid metabolism in high-fat diet (HFD)-fed mice. The primary mechanism by which BEP improves symptoms of glucose and lipid imbalances involves the modulation of gut microbiota. Key beneficial bacteria, including S24-7, Lachnospiraceae, [Prevotella], and Lactobacillus, were significantly enriched in the intestines of BEP-treated mice, with abundances 2.48-, 1.62-, 6.33- and 2.60-fold higher, respectively, compared to the HFD group. In contrast, the abundance of harmful bacteria, particularly Desulfovibrio, was reduced by 1.81-fold. These microbial shifts contributed to the alleviation of intestinal mucus layer damage and a 50 % reduction in serum lipopolysaccharide (LPS) levels, a key driver of systemic inflammation, compared to the HFD group. As a result, BEP effectively inhibited LPS-induced activation of the hepatic TLR4/Myd88/MAPK signaling pathway, thereby normalizing the expression of proteins related to glucose and lipid metabolism. A fecal microbiota transplantation study further demonstrated that the gut microbiota changes induced by BEP were central to its anti-metabolic syndrome effects. Overall, BEP may serve as a dietary supplement for preventing and treating diet-induced metabolism disorders by targeting the gut microbiota.

The gut microbiota is integral to an animal's physiology, influencing nutritional metabolism, immune function, and environmental adaptation. Despite the significance of gut microbiota in wild rodents, the Korean field mouse (Apodemus peninsulae) and the gray red-backed vole (Myodes rufocanus) remain understudied. To address this, a metagenomic sequencing analysis of the gut microbiome of these sympatric rodents in northeast China's temperate forests was conducted. Intestinal contents were collected from A. peninsulae and M. rufocanus within the Mudanfeng National Nature Reserve. High-throughput sequencing elucidated the gut microbiome's composition, diversity, and functional pathways. Firmicutes, Bacteroidetes, and Proteobacteria were identified as the dominant phyla, with M. rufocanus showing greater microbiome diversity. Key findings indicated distinct gut bacterial communities between the species, with M. rufocanus having a higher abundance of Proteobacteria. The gut microbiota of A. peninsulae and M. rufocanus differed marginally in functional profiles, specifically in the breakdown of complex carbohydrates, which might reflect their distinct food preferences albeit both being herbivores with a substantial dietary overlap. The investigation further elucidated gut microbiota's contributions to energy metabolism and environmental adaptation mechanisms. This study aligns with information on rodent gut microbiota in literature and highlights the two understudied rodent species, providing comparative data for future studies investigating the role of gut microbiota in wildlife health and ecosystem functioning.

Salivary microbiome alterations are associated with chronic diseases, such as cardiovascular disease, diabetes, and dementia. These chronic diseases often coexist in older adults, leading to polypharmacy. This situation complicates the relationship between systemic diseases and salivary microbiome dysbiosis. Previous studies have demonstrated the association of the human gut microbiome with common prescription drug use, including polypharmacy. However, a comprehensive analysis of the salivary microbiome and prescription drugs is yet to be conducted in older adults. Therefore, in this study, we performed a multivariate analysis to investigate the relationship between salivary microbiomes and host variables, including prescribed drugs, cognitive function, and oral health, in Japanese older adults with different disease backgrounds.

We enrolled non-hospitalised 82 older adults aged ≥70 years from a Japanese village community, and collected metadata, including age, sex, body mass index, cognitive function, oral health, alcohol consumption, smoking, and common prescription drug information. We performed multivariate analyses and functional predictions on the salivary microbiome based on 16S ribosomal RNA gene amplicon sequencing, including the metadata as potential confounders.

We observed a relationship between the human salivary microbiome and prescribed drug use in Japanese older adults with a heterogeneous background of comorbidities. The effects of several prescribed drugs, such as statins, proton pump inhibitors, and transporter/symporter inhibitors, on the salivary microbiome diversity were more prominent than those of host variables, including age, sex, and oral health. Notably, statin use was strongly correlated with a decrease in the Streptococcus abundance. Furthermore, statin intensity and obesity may be associated with altering the salivary microbiome, including functional predictions for vitamin biosynthesis and purine nucleotide degradation pathways in statin users.

Our multivariate analysis, adjusted for prescribed drug use and non-use, revealed the drug-specific alteration of salivary microbiome composition in Japanese older adults with comorbidities. To our knowledge, this study is the first to described the association of common prescription drug use with salivary microbiome alterations in older adults. Our findings indicated that prescribed drug use is a key factor in understanding the link between salivary microbiome changes and systemic diseases in older adults.

Live biotherapeutic products (LBPs) are biological products composed of living micro-organisms, developed to prevent, treat, or cure diseases. Examples include cultured strains of Akkermansia muciniphila and Christensenella minuta, as well as treatments using purified Firmicutes spores for recurrent Clostridioides difficile infections. There is a need for guidelines over the increasing interest in developing LBPs. A panel of microbiome experts from Asia-Pacific countries articulates their perspectives on key considerations for LBP development.

Experts in microbiome research, microbiology, gastroenterology, internal medicine and biotherapeutics industry were invited to form a panel. During the 2023 Inauguration Conference of the Asia-Pacific Microbiota Consortium, an organised, iterative roundtable discussion was conducted to build expert consensus on critical issues surrounding the development of LBP.

The consensus statements were organised into three main aspects: (a) rationales of LBP development, (b) preclinical studies and (c) preparation for clinical studies. The panel strongly recommended to prioritise human-derived and food-sourced strains for development, with indications based on clinical need and efficacy shown in studies. Preclinical evaluation should involve thorough screening, genotyping and phenotyping, as well as comprehensive in vitro and animal studies to assess functional mechanisms and microbiological safety. Rigorous cell banking practices and genetic monitoring are essential to ensure product consistency and safety throughout the manufacturing process. Clinical trials, including postmarketing surveillance, must be carefully designed and closely monitored, with robust safety and risk management protocols in place.

The development of LBP should be approached with a strong emphasis on microbiological evaluation, clinical relevance, scientific mechanisms and safety at every stage. These measures are essential to ensure the safety, effectiveness and long-term success of the product.

Obesity, characterized by excessive fat accumulation, stems from an imbalance between energy intake and expenditure, with the gut microbiota playing a crucial role. This review highlights how gut microbiota influences metabolic pathways, inflammation, and adipose tissue regulation in obesity. Specific bacteria and metabolites, such as lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs), modulate gut permeability, inflammation, and energy harvest, impacting obesity development. Certain gut bacteria, including Clostridium XIVb, Dorea spp., Enterobacter cloacae, and Collinsella aerofaciens, promote obesity by increasing energy harvest, gut permeability, and inflammatory response through LPS translocation into the bloodstream. Conversely, beneficial bacteria like Akkermansia muciniphila, Lactobacillus spp., and Bifidobacterium spp. enhance gut barrier integrity, regulate SCFA production, and modulate fasting-induced adipose factor, which collectively support metabolic health by reducing fat storage and inflammation. Metabolites such as SCFAs (acetate, propionate, and butyrate) interact with G-protein coupled receptors to regulate lipid metabolism and promote the browning of white adipose tissue (WAT), thus enhancing thermogenesis and energy expenditure. However, LPS contributes to insulin resistance and fat accumulation, highlighting the dual roles of these microbial metabolites in both supporting and disrupting metabolic function. Therapeutic interventions targeting gut microbiota, such as promoting WAT browning and activating brown adipose tissue (BAT), hold promise for obesity management. However, personalized approaches are necessary due to individual microbiome variability. Further research is essential to translate these insights into microbiota-based clinical therapies.

Obesity is a major healthcare problem worldwide and is induced by excess energy intake, resulting in gut microbial composition and microbial diversity changes. Through fermentation of dietary fibers, short-chain fatty acids (SCFAs) act as host energy sources and signaling molecules via G protein-coupled receptors such as GPR41. Acidipropionibacterium acidipropionici is widely used in many applications; however, in vivo studies on the beneficial effect of A. acidipropionici via propionate production and host energy homeostasis are unclear. Therefore, this study aimed to investigate the beneficial metabolic effects of A. acidipropionici by focusing on GPR41 signaling in a high-fat diet (HFD)-induced obesity mouse model. Here, we demonstrated that A. acidipropionici OB7439 improved host metabolism in HFD-induced obesity in mice. The intake of A. acidipropionici OB7439 improved metabolism in HFD-induced obese mice by increasing propionate production, regulating glucose tolerance, and inhibiting hepatic inflammation via GPR41 signaling. Our findings shed light on the potential of using A. acidipropionici OB7439 as an SCFA producer for the prevention and treatment of metabolic disorders. Based on these results, we suggest that A. acidipropionici may be a potential therapeutic bacterium that inhibits obesity and modulates the gut microbial community.

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.

Selenium is an essential trace element for human health, but it mainly exists in an inorganic form that cannot be directly absorbed by the body. Brewer's yeast efficiently converts inorganic selenium into bioavailable organic selenium, making selenium-enriched yeast highly significant for human health research. Selenomethionine (SeM) is an important indicator for evaluating the quality of selenium-enriched yeast. Brewer's yeast was selected as the experimental subject, and the digestion of this yeast (Brewer's yeast) was simulated using an in vitro biomimetic gastrointestinal reactor to evaluate the effects of selenium-enriched yeast with various SeM levels on the gut flora of a healthy population. The experimental design comprised normal yeast (control group, OR), yeast containing moderate SeM levels (selenium-enriched group, SE), yeast containing high SeM levels (high-selenium group, MU), and a commercially available group comprising selenium-enriched yeast tablets (MA). The MU group exhibited a significantly higher concentration of short-chain fatty acids than the OR and MA groups during 48 h of fermentation, with significant differences observed (p < 0.05). Sequencing results revealed that the MU group showed significantly increased relative abundances of Bacteroidetes and Actinobacteria, while exhibiting a decreased ratio of Firmicutes to Bacteroidetes, which may simultaneously affect multiple metabolic pathways in vivo. These findings support the theory that selenium-enriched yeast with a high SeM has a more positive effect on human health compared with traditional yeast and offer new ideas for the development and application of selenium-enriched yeast.

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.

Research links gut microbiota to postoperative delirium (POD) through the gut-brain axis. However, changes in gut microbiota and fecal short-chain fatty acids (SCFAs) in POD patients during the perioperative period and their association with POD are unclear.

We conducted a nested case-control study among patients undergoing off-pump coronary artery bypass grafting, focusing on POD as the main outcome. POD patients were matched 1:1 with non-POD patients based on sociodemographic characteristics, health, and diet. Fecal samples were collected pre- and post-surgery to assess gut microbiota and SCFAs changes. Postoperative fecal samples were transplanted into antibiotic-treated mice to evaluate delirium-like behavior and neuroinflammation.

Out of 120 patients, 60 were matched. Before surgery, gut microbiota in both groups was similar. After surgery, POD patients had lower alpha diversity and distinct microbiota compared to non-POD patients. LEfSe analysis showed POD was linked to increased opportunistic pathogens (Enterococcus) and decreased SCFAs producers (Bacteroides, Ruminococcus, etc.). SCFAs were significantly reduced in POD patients and negatively correlated with delirium severity and plasma inflammation. Mice receiving fecal transplants from POD patients exhibited delirium-like behavior and neuroinflammation.

Postoperative delirium is associated with gut microbiota dysbiosis, marked by an increase in opportunistic pathogens and a decrease in SCFA-producing genera.

Chinese Clinical Trial Registry ChiCTR2300070477.

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.

Domestic ducks are economically important agricultural animals, and their body size is a crucial economic trait. The intestinal flora plays a pivotal role in influencing body metabolism, growth, and development. Currently, no literature is available on the potential effect of the intestinal flora of domestic ducks on body size. This study used 16S rRNA sequencing technology to investigate the fecal microbiota of 229 individuals reared under identical feeding conditions. The findings revealed that partridge ducks with large body sizes (LBS) exhibited a higher level of intestinal microbial diversity than ducks with small body sizes (SBS). Notably, the gut microbiota composition of SBS displayed significantly elevated proportions of Streptococcus, Rothia, and Psychrobacter compared to their counterparts with LBS. Conversely, Lactobacillus was significantly more abundant in LBS. Jeotgalibaca and Psychrobacter were identified as key biomarkers of SBS, whereas Lactobacillus and Bacteroides were predominant biomarkers of LBS. Functional predictions based on intestinal microbiota indicated discernible differences among different body types, particularly evident in non- partridge ducks. The present study investigated the correlation between the intestinal microbiota and body size of domestic ducks, aiming to provide practical insights for the production management of domestic duck farming.