Competitive sports and sports nutrition, popular among amateur athletes aiming for a lean physique, have limited research on gut microbiota.

We conducted a 46-week study to analyze the consequences of fat loss and diet restrictions in 23 fitness athletes who prepared for a physique competition. Body composition, dietary intakes, serum cytokines and chemokines, and fecal samples were analyzed.

Fat loss through caloric restriction and aerobic exercise led to an increased phylogenetic diversity of gut microbiota and changes in the composition of gut microbiota, with Faecalibacterium, Lachnospiraceae, Bacteroides, and Intestinimonas showing altered abundances. Fat loss also changed the predicted microbial functions responsible for the metabolism of carbohydrates and amino acids. Consumption of energy, carbohydrates, fiber, vitamins and minerals, and various fatty acids decreased during the preparation for the competition, which was partly associated with changes in gut microbiota. Several cytokine levels decreased (IL1a, IL1b, IL10, and TFNα), and certain chemokine levels increased (GROa and RANTES). During the 23-week regain period after the competition, gut microbiota showed signs of recovery, with increased diversity compared to pre- and post-competition measurements. Most taxonomic changes returned to their baseline levels after the regain period.

The study highlights the dynamic nature of gut microbiota and its response to fat loss and regain in non-obese fitness/physique competitors and provides novel insights into how competitive sports and sports nutrition can influence the gut ecosystem.

Bariatric surgery is highly effective in achieving weight loss in children and adolescents with severe obesity, however the underlying mechanisms are incompletely understood, and gut microbiome changes are unknown. Here, we show that adolescents exhibit significant gut microbiome and metabolome shifts several months after laparoscopic vertical sleeve gastrectomy (VSG), with increased alpha diversity and notably with enrichment of oral-associated taxa. To assess causality of the microbiome/metabolome changes in phenotype, pre-VSG and post-VSG stool was transplanted into germ-free mice. Post-VSG stool was not associated with any beneficial outcomes such as adiposity reduction compared pre-VSG stool. However, post-VSG stool exhibited a potentially inflammatory phenotype with increased intestinal Th17 and decreased regulatory T cells. Concomitantly, we found elevated fecal calprotectin and an enrichment of proinflammatory pathways in a subset of adolescents post-VSG. We show that in some adolescents, microbiome changes post-VSG may have inflammatory potential, which may be of importance considering the increased incidence of inflammatory bowel disease post-VSG.

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.

Monosodium glutamate (MSG) has become one of the most widely used food additives in the global food supply. Although it has been classified for decades as a food ingredient that is generally recognized as safe, concerns about the health impacts of chronic MSG use, especially its potential effect on weight, are still ongoing. This comprehensive review summarizes the available human and animal evidence, highlighting potential mechanisms linking MSG use to weight gain or obesity, and discusses challenges and future research directions. Because of MSG intake worldwide as well as hidden MSG in food labeling, there is a pressing need for a mechanistic understanding of the health impacts of MSG use especially on weight. To generate robust scientific evidence and to clarify public concerns, rigorous mechanistic studies and randomized controlled clinical trials are warranted.

Anorexia nervosa (AN) is a debilitating and often refractory eating disorder that is unique among psychiatric disorders insofar as nutrition is key to recovery. Treatment options and efficacy are limited with no approved medications for AN. Genetic studies are clarifying the etiology of AN, with the goal of eventually informing the development of innovative personalized pharmacologic, nutritional, microbial, and behavioral interventions. We present the current state of genome-wide and epigenome-wide association studies, gut microbiome research, and functional genomics investigations and discuss translating this knowledge into clinical practice.

The increased prevalence of hyperlipidemia significantly affects human health worldwide. Although drug treatment is very effective, the harm to the human body cannot be ignored. Improvement of lipid metabolism by natural medicinal and food homologous products is an effective approach to ameliorate hyperlipidemia and it has gradually become a research focus. In this research, we adopted HepG2 cell models and high-fat-diet-fed C57BL/6j mouse models to explore the effect of hawthorn total flavonoids (HTF) on hyperlipidemia. Moreover, we utilized western blot and gut microbiota analysis to elucidate the specific mechanism of HTF's influence on hyperlipidemia.

We found that HTF significantly alleviated hyperlipidemia and its complications, as manifested by reduced body weight gain and fat accumulation, and improved the disorder of intestinal microorganisms. HTF protected the liver, reducing aspartate transaminase and lactate dehydrogenase levels, and ameliorating inflammatory infiltration. Fat droplet amounts and necrotic cell numbers in liver cells were also decreased. Mechanistically, HTF promoted AMP-activated protein kinase phosphorylation, inhibited sterol regulatory element binding protein 1c expression, downregulating the expression of lipid synthesis-related proteins (acetyl CoA carboxylase, fatty acid synthase, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase), thus suppressing liver lipid synthesis. HTF also functioned as a natural peroxisome proliferator-activated receptor α (PPARα) agonist. Activated PPARα enhanced mitochondrial oxidation and lipid consumption via upregulating carnitine palmitoyltransferase 1A. Peroxisome proliferator-activated receptor-γ coactivator expression was also elevated, activating mitochondrial activity, increasing cholesterol 7α-hydroxylase activity and cholesterol consumption, and reducing blood lipids. Additionally, HTF regulated intestinal flora abundance, restored the ratio of Firmicutes to Bacteroidetes, balanced gut-liver axis crosstalk, and alleviated hyperlipidemia.

The results demonstrated that HTF alleviated the pathological symptoms caused by hyperlipidemia, and had a certain protective effect on the liver. HTF also stimulated the lipid metabolism pathway and accelerated lipid consumption. © 2025 Society of Chemical Industry.

Evidence suggests that increased distal short-chain fatty acid (SCFA) production beneficially impacts metabolic health. However, indigestible carbohydrate availability is limited in the distal colon; consequently, microbes shift toward protein fermentation, often linked to adverse metabolic health effects. We aimed to identify specific fiber(s) that promote saccharolytic fermentation in the distal colon and thereby may (partially) inhibit proteolytic fermentation.

Potato-fiber, pectin, and inulin were studied individually and in combination against a high (predigested) protein background using an in vitro model of the colon (TIM-2) inoculated with pooled, standardized fecal microbiota from individuals with overweight/obesity. Microbiota composition and activity were assessed at different timepoints to simulate the travel throughout the colon (proximal: 0-8 h, distal: 8-24 h) and compared to a high protein (HP)_control, receiving only proteins.

Fiber addition increased total SCFA production compared to HP_control (52.11 ± 1.49 vs 27.07 ± 0.26 mmol) whereas total branched-chain fatty acids (BCFA; a marker for protein fermentation) production only slightly decreased (3.31 ± 0.10 vs 4.18 ± 0.40 mmol). Combining potato-fiber and pectin led to the highest total and distal SCFA production and distal SCFA:BCFA. Fiber addition attenuated HP-induced increases in several bacterial taxa including Mogibacterium and Coprococcus, independent of fiber type. Additionally, time- and fiber-specific microbial signatures were identified: inulin increased Bifidobacterium (proximal) relative abundance and pectin and/or potato-fiber increased Prevotella 9 (distal) relative abundance.

The most marked increase in distal colonic SCFA production was induced by combining potato-fiber and pectin. Further research should elucidate whether this switch toward saccharolytic fermentation translates into beneficial metabolic health effects in humans.

The gut microbiome comprises trillions of microorganisms and profoundly influences human health by modulating metabolism, immune responses and neuronal functions. Disruption in gut microbiome composition is implicated in various inflammatory conditions, metabolic disorders and neurodegenerative diseases. However, determining the underlying mechanisms and establishing cause and effect is extremely difficult. Preclinical models offer crucial insights into the role of the gut microbiome in diseases and help identify potential therapeutic interventions. The Human Microbiome Action Consortium initiated a Delphi survey to assess the utility of preclinical models, including animal and cell-based models, in elucidating the causal role of the gut microbiome in these diseases. The Delphi survey aimed to address the complexity of selecting appropriate preclinical models to investigate disease causality and to study host-microbiome interactions effectively. We adopted a structured approach encompassing a literature review, expert workshops and the Delphi questionnaire to gather insights from a diverse range of stakeholders. Experts were requested to evaluate the strengths, limitations, and suitability of these models in addressing the causal relationship between the gut microbiome and disease pathogenesis. The resulting consensus statements and recommendations provide valuable insights for selecting preclinical models in future studies of gut microbiome-related diseases.

Mas, a newly identified G-protein-coupled receptor, is prevalent in myeloid-derived immune cells and plays a key role in inflammation. This study investigates Mas signaling and neutrophil extracellular traps (NETs) in acute liver failure (ALF), aiming to elucidate their mechanisms. Male Mas1-/- and wild-type mice, aged 6-8 weeks, receive intraperitoneally injected with lipopolysaccharide (LPS)/D-galactosamine (D-Gal) (L/G) to study NETs formation. Hepatic Mas expression increases in WT-L/G mice, whereas systemic Mas1 knockout significantly reduces L/G-induced NETs and hepatotoxicity. Antibiotics treatment and co-housing (Mas1-/--L/G and WT-L/G mice) experiments show that gut flora influences the disease phenotype in Mas1-/--L/G mice. Fecal metabolite analysis suggests that mice may be protected by reduced deoxycholic acid (DCA) production in Mas1-/- activated hepatic farnesoid X receptor (FXR), suppressing sphingosine-1-phosphate (S1P)-dependent NETs. Additionally, Mas1-/- also activates the FXR-S1P-NETs axis in the liver by inhibiting SHP2. Single-cell sequencing shows decreased interaction between endothelial cells and Cldn1+CD177+ senescent neutrophils through Col4a1-CD44. This inhibits S1P-induced Raf signaling pathway activation and NETs formation. Mas signaling significantly impacts NETs formation, highlighting its potential as an anti-inflammatory therapeutic target for ALF.

Over the past few decades, obesity has transitioned from a localized health concern to a pressing global public health crisis affecting over 650 million adults globally, as documented by WHO epidemiological surveys. As a chronic metabolic disorder characterized by pathological adipose tissue expansion, chronic inflammation, and neuroendocrine dysregulation that disrupts systemic homeostasis and impairs physiological functions, obesity is rarely an isolated condition; rather, it is frequently complicated by severe comorbidities that collectively elevate mortality risks. Despite advances in nutritional science and public health initiatives, sustained weight management success rates and prevention in obesity remain limited, underscoring its recognition as a multifactorial disease influenced by genetic, environmental, and behavioral determinants. Notably, the escalating prevalence of obesity and its earlier onset in younger populations have intensified the urgency to develop novel therapeutic agents that simultaneously ensure efficacy and safety. This review aims to elucidate the pathophysiological mechanisms underlying obesity, analyze its major complications-including type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), non-alcoholic fatty liver disease (NAFLD), obesity-related respiratory disorders, obesity-related nephropathy (ORN), musculoskeletal impairments, malignancies, and psychological comorbidities-and critically evaluate current anti-obesity strategies. Particular emphasis is placed on emerging pharmacological interventions, exemplified by plant-derived natural compounds such as berberine (BBR), with a focus on their molecular mechanisms, clinical efficacy, and therapeutic advantages. By integrating mechanistic insights with clinical evidence, this review seeks to provide innovative perspectives for developing safe, accessible, and effective obesity treatments.

It is known that microbiome and health are related, in addition, recent research has found that microbiome has potential clinical uses. These facts highlight the importance of the microbiome in actual science. However, microbiome data has some characteristics that makes its statistical study challenging. In recent years, longitudinal and non-longitudinal methods have been designed to analyze the microbiota and knowing more about the bacterial behavior. In this article in the form of a review we summarize the characteristics of microbiome data and the statistical methods most widespread to analyze it. We have taken into account if the strategies are longitudinal or not. We also classify the methods based on their specific analytical objectives and based on their mathematical characteristics. The methods are structured according to their biological goals and mathematical features, ensuring that the insights provided are both relevant and accessible to professionals in biology and statistics. We present this review as a reference for the most widely used methods in microbiome data analysis and as a foundation for identifying potential areas for future research. We want to point out that this review can be particularly useful to remark the importance of the methodology designed in order to study microbiome longitudinal datasets.

This study aimed to investigate the efficacy of polysaccharides from Artemisia sphaerocephala Krasch (ASK) seed in alleviating high fat diet (HFD) caused obesity. Here, three polysaccharide fractions (ASKP1, ASKP2 and ASKP3) were purified from ASK seed. Chemical characteristic analysis revealed that ASKP1 is a neutral heteropolysaccharide with the average molecular weight of 9.08 × 105 Da, while ASKP2 and ASKP3 are acidic heteropolysaccharides with the molecular weight of 9.39 × 105 and 8.41 × 105 Da, respectively. Animal experiment found that three ASKP fractions obviously relieved obesity and related metabolic disorders induced by HFD, while ASKP1 was more effective in reducing the blood glucose and serum LDL levels. 16S rDNA sequencing showed that ASKP fractions improved the gut microbiota imbalance of obese mice, and ASKP1 promoted the proliferation of beneficial bacterium Akkermansia more effectively than ASKP2 and ASKP3. Furthermore, ASKP fractions facilitated thermogenesis of brown adipose tissue (BAT) of obese mice, as evidenced by increased expression of thermogenic marker genes UCP1 in BAT, and the thermogenesis effect of ASKP1 was the most obvious. Taken together, our results show that ASKP1 is a novel prebiotic that may be used to treat obesity and its related abnormal metabolism.

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.

Over time, extensive research has underscored the pivotal role of gut microbiota in the onset and progression of various diseases, with a particular focus on fecal microbiota transplantation (FMT) as a potential therapeutic approach. The practice of transferring fecal matter from a healthy donor to a patient provides valuable insights into how alterations in gut microbiota can impact disease development and how rectifying dysbiosis may offer therapeutic benefits. Re-establishing a balanced symbiotic relationship in the gastrointestinal tract has shown positive results in managing both intestinal and systemic conditions. Currently, one of the most pressing global health issues is metabolic syndrome-a cluster of conditions that includes insulin resistance, lipid imbalances, central obesity and hypertension. In this context, FMT has emerged as a promising strategy for addressing key components of metabolic syndrome, such as improving insulin sensitivity, body weight and lipid profiles. However, further well-structured studies are needed to refine treatment protocols and establish the long-term safety and efficacy of this intervention.

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).

Branched- chain fatty acids (BCFAs) are a category of saturated fatty acids that are commonly present in various organisms and play a crucial role in a variety of metabolic reactions, including anticancer, lipid-lowering, anti-inflammatory, and neuroprotective actions. Currently, there is growing interest in the relationship between BCFAs and obesity. Branched- chain fatty acids regulate the gene expression of related enzymes by activating PPARα and sterol regulatory element-binding protein-1c, thereby reducing triglyceride synthesis in the body. Additionally, BCFAs reduce inflammation by decreasing the expression of pro-inflammatory factors in obesity such as cyclooxygenase-2, interleukin-6, and lipoxygenase-15 genes. Branched- chain fatty acids can also expedite the conversion of branched chain amino acids to BCFAs to regulate obesity-induced insulin resistance. In this article we provide a comprehensive review of research progress on how BCFAs affect obesity from the perspectives of lipid metabolism, inflammation, and insulin resistance.

Previous observational studies have indicated a correlation between the skin microbiome and Type 2 diabetes (T2DM). It is hypothesized that this causal relationship may be influenced by inflammatory responses. However, these factors as determinants of T2DM remain largely unexplored.

This study incorporated data from the GWAS database on the skin microbiome, 91 types of inflammatory cytokines, and T2DM. We employed two-sample MR and multivariable MR methods to assess the correlation between the skin microbiome and T2DM, and to investigate whether this correlation is affected by inflammatory cytokines.

The results of the two-sample MR analysis indicate that within the skin microbiome, genetically predicted genus: Acinetobacter, class: Alphaproteobacteria, genus: Bacteroides, ASV005[Propionibacterium granulosum], and ASV072[Rothia mucilaginosa] are associated with an increased risk of T2DM, while phylum: Proteobacteria, genus: Enhydrobacter, family: Clostridiales, ASV006[Staphylococcus hominis] serve as protective factors against T2DM. Among the inflammatory cytokines, levels of Macrophage colony-stimulating factor 1, Tumor necrosis factor receptor superfamily member 9, Urokinase-type plasminogen activator, and C-C motif chemokine 28 are associated with an increased risk of T2DM. Multivariable MR analysis further revealed that Macrophage colony-stimulating factor 1 levels act as a mediating factor between ASV072[Rothia mucilaginosa] and T2DM.

In this study, we found a connection between the skin microbiome and T2DM, with inflammatory cytokines playing a key role in this relationship. This research helps us better understand this complex link and shows that addressing inflammation is important for preventing and treating diabetes. This could greatly benefit public health by reducing the impact of diabetes and its complications. Our results suggest that future studies should explore the specific biological interactions between the skin microbiome and diabetes to develop more effective risk management and treatment strategies from a microbial perspective.

Aleurone, derived from the bran layer of grains like wheat and barley, has demonstrated positive effects on energy metabolism in pigs, mice, and untrained horses, influencing glucose-insulin dynamics and gut microbiome composition. Training itself enhances insulin sensitivity in horses, similar to the improvements in performance capacity observed in human athletes. This study aimed to investigate whether aleurone supplementation provides additional benefits to training by modulating insulin metabolism and gut microbiota in Standardbred mares.

Sixteen Standardbred mares (aged 3-5 years) participated in a cross-over study with two 8-week training periods separated by 8 weeks of detraining. Each horse received either 200 g/day aleurone supplementation or a control diet. Insulin metabolism was evaluated using oral (OGTT) and intravenous (FSIGTT) glucose tolerance tests, measuring parameters such as Maximumglucose, AUCglucose, Maximuminsulin, AUCinsulin, Time to peakinsulin (OGTT), Acute Insulin Response to Glucose (AIRg), glucose effectiveness (Sg), and disposition index (DI) (FSIGTT). Fecal samples underwent metagenomic analysis to assess alpha and beta diversity and microbial composition.

Training alone: Training significantly improved OGTT parameters by decreasing Maximuminsulin (P = 0.005) and AUCinsulin (P = 0.001), while increasing Time to peakinsulin (P = 0.03), indicating enhanced insulin sensitivity. FSIGTT results also showed a decrease in logAIRg (P = 0.044). Training with Aleurone: Aleurone supplementation further reduced FSIGTT AIRg (P = 0.030), logAIRg (P = 0.021) while increasing glucose effectiveness (Sg; P = 0.031). These findings suggest aleurone improves insulin sensitivity, glucose disposal, and fasting glucose regulation beyond training. Microbiome analysis revealed training decreased Pseudomonas, associated with dysbiosis, while aleurone reduced inflammation-associated Desulfovibrio. Beta diversity metrics showed no significant changes.

Aleurone supplementation enhances training-induced improvements in glucose metabolism and fecal microbiota composition, which could offer potential benefits for equine athletes by optimizing metabolic flexibility. It also supports improvements in glucose and insulin dynamics, particularly by further enhancing insulin sensitivity and glucose-mediated disposal. Future studies should investigate the mechanisms of aleurone at the muscle and gut level and explore its potential applications for metabolic disorders such as Equine Metabolic Syndrome.

Type 2 diabetes mellitus (T2DM) is an obesity-related disease claiming substantial global mortality annually. Current animal models of T2DM remain limited, with low success rates in establishing porcine models of high-fat diet (HFD)-induced T2DM. Our experimental design employed 35 Guizhou mini-pigs to develop a T2DM model via HFD induction, aiming to identify microbial and metabolic signatures associated with disease pathogenesis and resistance. At month 10, five individuals from the control (CTR), T2DM (DM), and T2DM resistant (anti-DM) groups were slaughtered, samples were collected, and relevant indices were measured. Metagenomics, metabolomics, and 16S rRNA sequencing were performed to identify microbes and metabolites linked to T2DM progression and resistance. Key findings demonstrated anti-DM group parameters-including metabolic indices (fasting blood glucose, insulin levels, HbA1c, IVGTT), histopathology (HE-stained pancreatic/hepatic tissues), microbial profiles (structural, compositional, functional), and metabolomic signatures-occupied intermediate positions between CTR and DM groups. Network analyses revealed: (1) Lactobacillus, L. amylovorus, fingolimod, polyoxyethylene sorbitan monooleate, thiamine, and atrazine in HFD-associated networks; (2) Limosilactobacillus reuteri, N-oleoyl-L-serine, tolbutamide, tetradecanoyl carnitine, 3'-sulfogalactosylceramide, and guggulsterone in T2DM resistance networks; (3) Ruminococcaceae NK4A214 group, diethyl phthalate, zingerone, enalapril, 5-hydroxytryptophol, 2'-deoxyinosine, icariin, and emetine in T2DM progression networks. These results further clarify the role of the gut microbiota and serum metabolites in the development of T2DM in the Guizhou mini-pig model.

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.

Background/Objectives: The gut microbiota plays a pivotal role in host physiology through metabolite production, with lipids serving as essential biomolecules for cellular structure, metabolism, and signaling. This review aims to elucidate the interactions between gut microbiota and lipid metabolism and their implications for enhancing swine production. Methods: We systematically analyzed current literature on microbial lipid metabolism, focusing on mechanistic studies on microbiota-lipid interactions, key regulatory pathways in microbial lipid metabolism, and multi-omics evidence (metagenomic/metabolomic) from swine models. Results: This review outlines the structural and functional roles of lipids in bacterial membranes and examines the influence of gut microbiota on the metabolism of key lipid classes, including cholesterol, bile acids, choline, sphingolipids, and fatty acids. Additionally, we explore the potential applications of microbial lipid metabolism in enhancing swine production performance. Conclusions: Our analysis establishes a scientific framework for microbiota-based strategies to optimize lipid metabolism. The findings highlight potential interventions to improve livestock productivity through targeted manipulation of gut microbial communities.

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.

Mucins, heavily O-glycosylated glycoproteins, are a key component of mucus, and certain gut microbiota, including Akkermansia muciniphila, can utilise mucin glycans as a carbon source. Akkermansia muciniphila produces the O-glycopeptidase enzyme OgpA, which cleaves peptide bonds at the N-terminus of serine (Ser) or threonine (Thr) residues carrying O-glycan substitutions, with selectivity influenced by the O-glycan functional groups. Using molecular dynamics (MD) simulations and quantum chemistry calculations, we explored how different O-glycan groups affect OgpA's selectivity. Our results show that peptides bind to the enzyme via hydrogen bonds, π-π interactions, van der Waals forces and electrostatic interactions, with key residues, including Tyr90, Val138, Gly176, Tyr210 and Glu91, playing important roles. The primary determinant of selectivity is the interaction between the peptide's functional group and the enzyme's binding cavity, while peptide-enzyme interface interactions are secondary. Quantum chemistry calculations reveal that OgpA prefers peptides with a lower electrophilic character. This study provides new insights into mucin degradation by gut microbiota enzymes, advancing our understanding of this critical biological process.

Wild primates face a wide range of anthropogenic influences globally that impact their health, fitness, and survival. One area of potential impact that has been particularly understudied is the supplementation of wild primate diets with human foods. Although the consumption of human foods represents a substantial dietary change for wild primates, knowledge of how it impacts their physiology and behavior is limited. Here we explore how human food supplementation impacts wild primates by comparing the gut microbiomes of free-ranging brown howler monkeys (Alouatta guariba) in periurban Brazil that do or do not have access to human foods. We found that howler monkeys consuming human foods had reduced gut microbial diversity and reduced relative abundances of fiber degrading microbial taxa, which has been associated with negative health consequences in other animals, including humans. However, the effect size of these differences was relatively small and varied over time. Additionally, the composition of the gut microbiome varied significantly across months, regardless of the access to human foods. We suggest that the biology of this howler monkey population is minimally impacted by human foods. Further empirical research will help clarify the relationship between human food supplementation and health across primate populations, facilitating conservation applications.

Synthetic glycans (SGs) containing glycosidic linkages and structures not identified in nature offer a means for deliberately altering microbial community properties. Here pools of SG oligosaccharides were generated via polymerization of monosaccharides and screened for their ability to increase saccharolytic Bacteroides in ex vivo cultures of human fecal samples. A lead SG preparation was orally administered to gnotobiotic mice harboring a consortium of 56 cultured, phylogenetically diverse human gut bacteria and fed a Western diet. The abundances of 3 of 15 Bacteroides strains increased, most prominently B. intestinalis. Underlying mechanisms were characterized by analyzing in vivo expression of the carbohydrate utilization machinery, using retrievable microscopic paramagnetic particles with bound SG oligosaccharides and assaying SG degradation by individual purified B. intestinalis glycoside hydrolases. The results reveal that SGs can selectively co-opt carbohydrate utilization machinery in different human gut Bacteroides and demonstrate a means for identifying artificial carbohydrate structures for targeted bacterial manipulation.

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.

This study introduces a deep learning-based strategy to automatically detect the L3 slice and segment abdominal tissues from computed tomography (CT) images. Accurate measurement of muscle and fat composition at the L3 level is critical as it can serve as a prognostic biomarker for cancer diagnosis and treatment. However, current manual approaches are time-consuming and prone to class imbalance, since L3 slices constitute only a small fraction of the entire CT dataset. In this study, we propose an optimization-incorporated strategy that integrates augmentation ratio and class weight adjustment as correction design variables within deep learning models. In this retrospective study, the CT dataset was privately collected from 150 prostate cancer and bladder cancer patients at the Department of Urology of Gangneung Asan Hospital. A ResNet50 classifier was used to detect the L3 slice, while standard Unet, Swin-Unet, and SegFormer models were employed to segment abdominal tissues. Bayesian optimization determines optimal augmentation ratios and class weights, mitigating the imbalanced distribution of L3 slices and abdominal tissues. Evaluation of CT data from 150 prostate and bladder cancer patients showed that the optimized models reduced the slice detection error to approximately 0.68 ± 1.26 slices and achieved a Dice coefficient of up to 0.987 ± 0.001 for abdominal tissue segmentation-improvements over the models that did not consider correction design variables. This study confirms that balancing class distribution and properly tuning model parameters enhances performance. The proposed approach may provide reliable and automated biomarkers for early cancer diagnosis and personalized treatment planning.

The Gansu zokor (Eospalax cansus), a subterranean rodent endemic to the Loess Plateau of China, exhibits remarkable adaptability to hypoxic environments. While gut microbiota are known to regulate lipid metabolism through bile acid (BA) pathways, this phenomenon has not been investigated in subterranean rodents exposed to hypoxia. This study employed 16SrRNA sequencing, targeted analysis of BA metabolites in colonic contents, and assessments of BA and lipid metabolites alongside molecular analyses in the liver and ileum under conditions of acute and chronic hypoxia in Gansu zokors. The results revealed that hypoxia altered the composition of gut microbiota and BA pools in Gansu zokors. Hypoxia-induced changes increased the abundance of gut microbiota associated with BA metabolism, thereby modulating lipid metabolism via farnesoid X receptor (FXR) signaling in the distal ileum and liver cells. Under acute hypoxia, FXR upregulated lipid synthesis and suppressed fatty acid β-oxidation by downregulating the carnitine palmitoyl-transferase1A (CPT1A) expression. Conversely, during chronic hypoxia, particularly under long-term exposure, FXR reduced lipid synthesis and enhanced fatty acid β-oxidation by upregulating acyl-CoA oxidase (ACOX1) expression. In both hypoxic conditions, FXR facilitated lipoprotein metabolism. In summary, this study elucidates that gut microbiota-mediated BA metabolic pathways contribute to the Gansu zokor's ability to maintain lipid metabolic homeostasis and adaptation to hypoxia.

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.

Fecal microbiota transplantation (FMT) represents a therapeutic approach that directly regulates the gut microbiota of recipients, normalizes its composition and reaping therapeutic rewards. Currently, in addition to its general application in treating Clostridium difficile (C. difficile) infection (CDI), FMT treatment has also been extended to the fields of other gastrointestinal diseases, infections, gut-liver or gut-brain axis disorders, metabolic diseases and cancer, etc. Prior to FMT, rigorous donor screening is essential to reduce the occurrence of adverse events. In addition, it is imperative to evaluate whether the recipient can safely and effectively undergo FMT treatment. However, the efficacy of FMT is influenced by the complex interactions between the gut microbiota of donor and recipient, the degree of donor microbiota engraftment is not necessarily positively related with the success rate of FMT. Furthermore, an increasing number of novel factors affecting FMT outcomes are being identified in recent clinical trials and animal experiments, broadening our understanding of FMT treatment. This article provides a comprehensive review of the application scenarios of FMT, the factors influencing the safety and efficacy of FMT from the aspects of both the donors and the recipients, and summarizes how these emerging novel regulatory factors can be combined to predict the clinical outcomes of patients undergoing FMT.

The gut microbiota is closely associated with the onset and development of type 2 diabetes mellitus (T2DM), characterized by insulin resistance (IR) and chronic low-grade inflammation. However, despite the widespread use of first-line antidiabetic drugs, IR in diabetes and its complications continue to rise. The gut microbiota and its metabolic products may promote the development of T2DM by exacerbating IR. Therefore, regulating the gut microbiota has become a promising therapeutic strategy, with particular attention given to probiotics, prebiotics, synbiotics, and fecal microbiota transplantation. This review first examines the relationship between gut microbiota and IR in T2DM, summarizing the research progress of microbiota-based therapies in modulating IR. We then delve into how gut microbiota-related metabolic products contribute to IR. Finally, we summarize the research findings on the role of traditional Chinese medicine in regulating the gut microbiota and its metabolic products to improve IR. In conclusion, the gut microbiota and its metabolic products play a crucial role in the pathophysiological process of T2DM by modulating IR, offering new insights into potential therapeutic strategies for T2DM.

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.

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with significant challenges in diagnosis and treatment. Recent research has highlighted the complex nature of ALS, encompassing behavioral impairments in addition to its neurological manifestations. While several medications have been approved to slow disease progression, ongoing research is focused on identifying new therapeutic targets. The current review focuses on emerging therapeutic strategies and personalized approaches aimed at improving patient outcomes. Recent advancements highlight the importance of targeting additional pathways such as mitochondrial dysfunction and neuroinflammation to develop more effective treatments. Personalized medicine, including genetic testing and biomarkers, is proving valuable in stratifying patients and tailoring treatment options. Complementary therapies, such as nutritional interventions like the ketogenic diet and microbiome modulation, also show promise. This review emphasizes the need for a multidisciplinary approach that integrates early diagnosis, targeted treatments, and supportive care to address the multisystemic nature of ALS and improve the quality of life for patients.

The stability and metabolic functionality of donor microbiota are critical determinants of fecal microbiota transplantation (FMT) efficacy in inflammatory bowel disease (IBD). While probiotics show potential to enhance microbiota resilience, their role in optimizing donor microbiota for FMT remains underexplored.

This study investigated whether pretreatment of donor microbiota with L. plantarum GR-4 could improve FMT outcomes in a DSS-induced colitis model by modulating microbial stability, metabolic activity, and host-microbiome interactions.

Donor mice received L. plantarum GR-4 for 3 weeks to generate modified FMT (MFMT). DSS-colitis mice were treated with MFMT, conventional FMT, or 5-aminosalicylic acid (5-ASA). Multi-omics analyses and functional assays (stress resistance, engraftment efficiency) were used to evaluate therapeutic mechanisms.

GR-4 pretreatment conferred three key advantages to donor microbiota: Ecological stabilization: 1. GR-4-driven acidification (pH 3.97 vs. 4.59 for LGG, p < 0.0001) enriched butyrogenic Butyricicoccus (73 % butyrate increase, p < 0.05) and improved stress resistance to bile acids/gastric conditions (1.25 × survival vs. FMT). 2. Metabolic reprogramming: GR-4 metabolized 25.3 % of tryptophan (vs. 10.3 % for LGG) to generate immunomodulatory indoles (ILA, IAA), activating aryl hydrocarbon receptor (AHR) signaling and upregulating anti-inflammatory IL-10/IL-22. 3. Bile acid remodeling: MFMT restored sulfolithocholic acid and β-MCA levels, outperforming FMT in resolving DSS-induced dysregulation. MFMT achieved an 83 % remission rate (vs. 50 % for FMT), enhanced gut barrier integrity, and reversed colitis-associated metabolic dysregulation (e.g., elevated spermidine, 7-sulfocholic acid). Probiotic preconditioning improved donor engraftment by 1.25 × and enriched success-associated taxa (Sporobacter, Butyricimonas), while suppressing pathogens (Clostridium papyrosolvens).

L. plantarum GR-4 optimizes donor microbiota via pH-driven niche engineering, immunometabolic reprogramming, and bile acid modulation, addressing key limitations of conventional FMT. The multi-targeted efficacy of MFMT, evidenced by superior remission rates and metabolic restoration, establishes this approach as a translatable strategy for IBD therapy. This study establishes probiotic-enhanced FMT as a paradigm for precision microbiome interventions.

The upper and lower respiratory tracts feature distinct environments and responses affecting microbial colonization but investigating the relationship between them is technically challenging. We aimed to identify relationships between taxa colonizing the nasopharynx and trachea across childhood.

We employed V4 16S rRNA gene sequencing to profile nasopharyngeal swabs and tracheal aspirates collected from 172 subjects between 20 weeks and 18 years of age. These samples were collected prior to elective procedures over the course of 20 weeks in 2020 from subjects enrolled in a cross-sectional study. After extraction, sequencing, and quality control, we studied the remaining 147 of 172 nasopharyngeal swabs and 95 of 172 tracheal aspirates, including 80 subject-matched pairs of samples.

Sequencing data revealed that the nasopharynx is colonized by few, often highly abundant taxa, while the tracheal aspirates feature greater diversity. The patterns of colonization identified in the nasopharynx correlate with subject age across childhood.

Our data suggests that there are relatively few species that colonize both the nasopharyngeal tract and the trachea. Furthermore, we observe a pattern of change in the nasopharyngeal microbiota that is correlated with age, suggesting a possible developmental progression of the nasopharyngeal microbiota across childhood.

The airway microbiota in childhood plays important roles in respiratory health and immune development. In this work, we report on paired nasopharyngeal swab and tracheal aspirate samples from a cross-sectional cohort of children from infancy to 18 years. We find that the upper and lower airway microbiota are unlikely to share taxa and do not correlate in terms of diversity. We show that the composition of the upper airway microbiota is strongly correlated with age, with a stereotypic developmental trajectory during childhood and adolescence. Our results inform our understanding of airway microbiota assembly and may be used to predict airway disease in young children.

In order to decipher the relationship between gut microbiota imbalance and cancer, this paper reviewed the role of intestinal microbiota in anticancer therapy and related mechanisms, discussed the current research status of gut microbiota as a biomarker of cancer, and finally summarized the reasonable means of regulating gut microbiota to assist cancer therapy. Overall, our study reveals that the gut microbiota can serve as a potential target for improving cancer management.