Osteoporosis is an age-related bone metabolic disease. As an essential endocrine organ, the skeletal system is intricately connected with extraosseous organs. The crosstalk between bones and other organs supports this view. In recent years, the link between the gut microecology and bone metabolism has become an important research topic, both in preclinical studies and in clinical trials. Many studies have shown that skeletal changes are accompanied by changes in the composition and structure of the gut microbiota (GM). At the same time, natural or artificial interventions targeting the GM can subsequently affect bone metabolism. Moreover, microbiome-related metabolites may have important effects on bone metabolism. We aim to review the relationships among the GM, microbial metabolites, and bone metabolism and to summarize the potential mechanisms involved and the theory of the gut‒bone axis. We also describe existing bottlenecks in laboratory studies, as well as existing challenges in clinical settings, and propose possible future research directions.

Roseburia intestinalis is one of the most abundant and important butyrate-producing human gut anaerobic bacteria that plays an important role in maintaining health and is a potential next-generation probiotic. We investigated the pangenome of 16 distinct strains, isolated over several decades, identifying local and time-specific adaptations. More than 50% of the genes in each individual strain were assigned to the core genome, and 77% of the cloud genes were unique to individual strains, revealing the high level of genome conservation. Co-carriage of the same enzymes involved in carbohydrate binding and degradation in all strains highlighted major pathways in carbohydrate utilization and reveal the importance of xylan, starch and mannose as key growth substrates. A single strain had adapted to use rhamnose as a sole growth substrate, the first time this has been reported. The ubiquitous presence of motility and sporulation gene clusters demonstrates the importance of these phenotypes for gut survival and acquisition of this bacterium. More than half the strains contained functional, potentially transferable, tetracycline resistance genes. This study advances our understanding of the importance of R. intestinalis within the gut ecosystem by elucidating conserved metabolic characteristics among different strains, isolated from different locations. This information will help to devise dietary strategies to increase the abundance of this species providing health benefits.

Obesity is reaching global epidemic proportions worldwide, posing a significant burden on individual health and society. Altered gut microbiota is considered a key factor in the pathogenesis of many diseases, producing metabolites that contribute to the health-beneficial properties of postbiotics. Postbiotics, bioactive microbial components derived from probiotics, are emerging as a valuable strategy in modern medicine and a promising alternative for managing obesity without the need for live bacteria. This work provides a comprehensive overview of the potential health benefits of postbiotics, particularly in relation to obesity, which represents an important health challenge. Despite the encouraging insights into the health benefits of postbiotics, we highlight the need for further research to clarify the mechanisms and the specific roles of different postbiotic components. Integrating postbiotics into health interventions has the potential to enhance preventive care and significantly improve health outcomes in at-risk populations.

Mucosal tissues, including those in the respiratory and gastrointestinal tracts, are critical barrier surfaces for pathogen invasion. Infections at these sites not only trigger local immune response, but also recruit immune cells from other tissues. Emerging evidence in the mouse models and human samples indicates that the immune crosstalk between the lung and gut critically impacts and determines the course of respiratory disease. Here we summarize the current knowledge of the immune crosstalk between the respiratory and gastrointestinal tracts, and discuss how immune cells are recruited and migrate between these tissues during respiratory infections. We also discuss how commensal bacteria contribute to these processes.

Obesity is a pro-inflammatory condition with negative effects on executive functioning. Increased inflammation dysregulates gastrointestinal homeostasis and alters microbiota community composition. The gut microbiota produce immunomodulatory short-chain fatty acids (SCFA) that have been related to cognition in obesity, but the neural effects are not explored. Here, we hypothesized that greater fecal SCFA would be positively related to neuroelectric markers of inhibitory control and conflict monitoring in obesity. A cross-sectional cohort of 87 adults (35 ± 6 years, 53 females) with overweight and obesity (BMI = 32 ± 6 kg/m2) provided fresh fecal samples and participated in cognitive testing to assess response inhibition and conflict monitoring with electroencephalographic recording. Linear regressions, controlling for age, sex, BMI, and energy-adjusted dietary fiber intake, revealed positive relationships between NoGo N2 mean amplitude and fecal SCFA concentrations. Linear discriminant analysis effect size (LEfSe) revealed 16 amplicon sequence variants differentially abundant between high and low butyrate groups with Roseburia and Adlercreutzia individually related to NoGo N2 mean amplitude in MaAsLin2 modeling. Thus, greater fecal SCFA concentrations and SCFA producing microbiota (i.e., Roseburia) were related to markers of superior conflict monitoring in the NoGo task when adjusting for key covariates. These data highlight key associations between bacterial derived gut signaling molecules and neural regulation in cognitive domains particularly relevant to weight status that warrant further investigation.

Background/Objectives: Type 2 diabetes (T2D) is a leading cause of morbidity and mortality worldwide and in Spain, particularly in the elderly population, affecting healthy ageing. Nutritional strategies are key to its prevention. The gut microbiota is also implicated in T2D and can be modulated by nutrition. We hypothesize that precision nutrition through microbiota modulation may help prevent T2D. This article aims to (1) describe a gut microbiota bacterial profile associated with T2D prevention, (2) provide precision nutrition tools to optimize this profile, (3) analyze how overweight influences the microbiota composition and precision nutrition response, and (4) address the technical challenges of microbiome-based precision nutrition clinical implementation to prevent T2D. Methods: A review of gut microbiota associated with T2D prevention was conducted. 13 healthy Spanish participants over 62 with optimal blood glucose levels (7 normal weight and 6 overweight) underwent a 3-month precision nutrition intervention to optimize T2D-preventive gut microbiota using a bioinformatics food recommendation system, Phymofood (EP22382095). Fecal microbiota was analyzed pre- and post-intervention using full-length 16S rRNA gene amplification, MinION sequencing, and NCBI taxonomic classification. Results: 31 potentially preventive bacteria against T2D were selected. The intervention increased the relative abundance of beneficial genera (Butyrivibrio and Faecalibacterium) and species (Eshraghiella crossota, and Faecalibacterium prausnitzii). The overweight influenced microbiota composition and intervention response. Conclusions: A gut microbiota profile associated with T2D prevention was identified, and precision nutrition could increase the relative abundance of beneficial bacteria. Confounding factors such as overweight should be considered when designing microbiome-based precision nutrition interventions. These results contribute to a better understanding of the microbiota associated with T2D prevention and address technical challenges for clinical implementation in future healthy ageing strategies.

Polygalae Radix has high pharmacological activity and has been widely used as a sedative and tranquilizer to increase cognitive function, prevent epilepsy, and treat respiratory diseases such as bronchitis. However, its role in delaying aging and decreasing oxidative stress and its main functional factors have not been thoroughly studied.

The purpose was to investigate the antiaging and antioxidant effects of aqueous Polygalae Radix extract (PRE) and its mechanism of action.

The effects of different concentrations (1, 5, and 10 mg/mL) of PRE on the lifespan, body length, reproductive ability, motility, lipofuscin, and reactive oxygen species (ROS) on a model of natural senescence of Caenorhabditis elegans were investigated. The effects of PRE treatment on the expression of body weight, malondialdehyde (MDA), glutathione peroxidase (GSH-PX), and mTERT content were evaluated in a D-galactose (Dgal)-induced mouse model of aging. Histopathological changes in the liver and brain of mice were analyzed by hematoxylin-eosin (HE). The enriched pathways associated with differentially expressed genes in the liver tissues of C. elegans and mice were analyzed via RNA-seq, and the results were verified via RT-qPCR, cell transfection and Western blotting. Abundance of and changes in the mouse intestinal flora were analyzed by 16S rDNA sequencing.

PRE significantly prolonged the average lifespan of C. elegans and improved the physiological indices related to senescence. In addition, PRE slowed the decrease in weight of senescent model mice; protected serum, liver and brain tissues from oxidative stress damage; increased GSH-PX expression; and reduced MDA expression. The role of PRE in the low- and middle-dose groups was similar to that of vitamin C (VC) in inhibiting oxidative stress, but the effect of PRE in the high-dose group was greater than that of VC. The RNA-seq results suggested that PRE might be related to PPARγ/MAPK, and the subsequent RT-qPCR and cell transfection results indicated that PRE decreased oxidative stress by downregulating the mRNA expression of the Fabp1, Acaa1b, Hmgcs1, Map3K5, and Rac2 genes. The Western blot results revealed that PRE decreased oxidative stress by increasing PPARγ expression and inhibiting p38 protein phosphorylation. 16S rDNA sequencing showed that PRE treatment increased the abundance of the intestinal flora in mice and inhibited the growth of pathogenic bacteria such as Helicobacter pylori and Desulfurization vibrio while promoting the growth of beneficial bacteria such as Bifidobacteria.

PRE delays aging and resists oxidative stress in organisms; it may act by regulating the PPARγ/MAPK signaling pathway and the intestinal flora. The efficacy and mechanism of PRE against oxidative stress were elucidated using RNA-seq and 16S rDNA sequencing, providing a reference for antiaging and aging-related diseases.

To investigate the role of intestinal flora and cholinergic anti-inflammatory pathways in the gut-brain axis, using oral gavage and intraperitoneal injection of methyllycaconitine (MLA). MLA was administered at a dose of 4 mg/kg for 30 days, either orally or via intraperitoneal injection. Rats were then assessed for behavioral changes, inflammatory markers, neurotransmitters, neuroreceptors, and intestinal mucosal barrier integrity. Rats receiving MLA via intraperitoneal injection exhibited significant behavioral abnormalities compared to the control and orally administered MLA groups. The levels of IL-1β were elevated in both intestinal and hippocampal tissues, while IL-10 levels were decreased. Brain-derived neurotrophic factor (BDNF) was significantly lower in hippocampal tissues. Furthermore, α7nAChR expression was reduced in hippocampal tissues, accompanied by an increase in 5-HT3A receptors. The intestinal mucosal barrier was compromised, as evidenced by reduced expression of ZO-1 and Occludin, along with increased IL-1β and decreased IL-10 levels in the gut. Our findings suggest that oral gavage of MLA does not induce cognitive impairment in rats compared to intraperitoneal injection, possibly due to the involvement of intestinal flora in the protective effects of CAP.

Background: Type 2 diabetes mellitus (T2DM) represents a major global health burden, with prevalence rates escalating due to rapid urbanization, economic growth, and the obesity epidemic. Despite intensive research, the underlying molecular mechanisms remain incompletely understood, with emerging evidence suggesting multifactorial origins involving genetic, epigenetic, lifestyle, and environmental factors. Methods: This review synthesizes current epidemiological data on T2DM prevalence, risk factors, and demographic patterns from 1990 to 2017, and discusses projected trends through 2030. We examine the role of intestinal barrier dysfunction and gut microbiota dysbiosis in T2DM pathogenesis, highlighting key mechanistic insights. Furthermore, we analyze recent findings on the role of butyrate, a major short-chain fatty acid, in preserving gut integrity and its potential therapeutic effects on metabolic health. Results: Global T2DM prevalence has risen markedly across all age groups, with particularly high rates in Western Europe and Pacific Island nations. Disruption of the intestinal barrier ("leaky gut") and gut microbiota alterations contribute significantly to systemic inflammation and insulin resistance, which are pivotal features in T2DM development. Butyrate plays a central role in maintaining epithelial barrier function, modulating immune responses, and regulating glucose metabolism. Preclinical studies have demonstrated that sodium butyrate supplementation improves gut integrity, reduces systemic endotoxemia, and ameliorates metabolic parameters. Emerging clinical evidence suggests benefits of sodium butyrate, particularly when combined with prebiotic fibers, in improving glycemic control and reducing inflammatory markers in T2DM patients. Conclusions: Gut barrier integrity and microbiota composition are critical factors in T2DM pathogenesis. Sodium butyrate shows promise as a complementary therapeutic agent in T2DM management, although further large-scale, long-term clinical trials are required to confirm its efficacy and safety. Targeting gut health may represent a novel strategy for the prevention and treatment of T2DM.

The arginine dihydrolase pathway (arc operon) provides a metabolic niche by transforming arginine into metabolic byproducts. We investigate the role of the arc operon in probiotic Escherichia coli Nissle 1917 on human gut community assembly and health-relevant metabolite profiles. By stabilizing environmental pH, the arc operon reduces variability in community composition in response to pH perturbations and frequently enhances butyrate production in synthetic communities. We use a tailored machine learning model for microbiomes to predict community assembly in response to variation in initial media pH and arc operon activity. This model uncovers the pH- and arc operon-dependent interactions shaping community assembly. Human gut species display altered colonization dynamics in response to the arc operon in the murine gut. In sum, our framework to quantify the contribution of a specific pathway to microbial community assembly and metabolite production can reveal new engineering strategies. A record of this paper's transparent peer review process is included in the supplemental information.

Dietary fiber, especially resistant starch (RS) Type 2 (RS2) found in high-amylose maize starch (HAMS), is vital for gut health and helps prevent colon cancer. In contrast to most nutrients, dietary fiber is not degraded by the intestinal enzymes; it reaches the distal parts of the gut, where it is fermented by the gut microbiota into short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate. SCFAs energize colonocytes, reduce inflammation, and enhance gut immunity. HAMS is absorbed in the colon, where it ferments to create SCFAs that feed good gut flora and have antiinflammatory and antiproliferative effects. RS2 in HAMS modulates gene signaling, activates tumor-suppressor genes like tumor suppressor protein (p53), exhibits antidiabetic, cholesterol-lowering, and antiinflammatory effects. Incorporation of RS2-rich sources enhances gut barriers, decreases colorectal cancer biomarkers, and counteracts the negative impacts of low-fiber Western diets, making HAMS a promising functional food for chronic disease prevention and health promotion.

Prebiotics are nondigestible carbohydrates fermented by gut bacteria into metabolites that confer health benefits. However, evidence on their role for inflammatory bowel disease (IBD) is unclear. This study systematically evaluated the research on prebiotics for treatment of IBD.

A search was performed in PubMed, Embase, Cochrane, and Web of Science. Eligible articles included randomized controlled trials or prospective observational studies that compared a prebiotic with a placebo or lower-dose control in patients with IBD. Meta-analyses were performed using random-effects models for the outcomes of clinical remission, clinical relapse, and adverse events.

Seventeen studies were included. For induction of clinical remission in ulcerative colitis (UC), the fructooligosaccharide (FOS) kestose was effective (relative risk, 2.75, 95% confidence interval, 1.05-7.20; n = 40), but oligofructose-enriched inulin (OF-IN) and lactulose were not. For maintenance of remission in UC, germinated barley foodstuff trended toward preventing clinical relapse (relative risk, 0.40; 95% confidence interval, 0.15-1.03; n = 59), but OF-IN, oat bran, and Plantago ovata did not. For Crohn's disease, OF-IN and lactulose were no different than controls for induction of remission, and FOS was no different than controls for maintenance of remission. Flatulence and bloating were more common with OF-IN; reported adverse events were otherwise similar to controls for other prebiotics.

Prebiotics, particularly FOS and germinated barley foodstuff, show potential as effective and safe dietary supplements for induction and maintenance of remission in UC, respectively. The overall certainty of evidence was very low. There would be benefit in further investigation on the role of prebiotics as treatment adjuncts for IBD.

Administering beneficial bacteria as probiotics to restore the intestinal microbiota and its metabolic functions, such as butyrogenesis, is a promising treatment strategy in ulcerative colitis (UC). This study aimed to investigate the effect of a combination of probiotics, consisting of the lactic acid bacterium Weizmannia coagulans SANK70258 and the lactate-utilizing butyrate-producing bacteria Anaerostipes caccae or Clostridium butyricum, on the colonic environment using an in vitro colonic microbiota culture model with fecal inoculums from seven patients with UC. Co-inoculated W. coagulans and A. caccae neither inhibited each other's growth nor significantly affected the relative abundance of other bacterial species; however, the growth of W. coagulans was significantly inhibited when co-inoculated with C. butyricum. The relative abundance of pro-inflammatory bacteria (Escherichia sp. and unclassified Enterobacteriaceae) and Bifidobacterium spp. significantly decreased in W. coagulans-C. butyricum co-inoculated cultures. Inoculation with any of the probiotics alone did not increase butyrate production, whereas co-inoculation of W. coagulans with A. caccae or C. butyricum significantly increased the butyrate levels. Overall, the results suggested that W. coagulans and lactate-utilizing butyrate-producing bacteria in combination have synergistic effects through cross-feeding and can effectively restore butyrogenesis in the colonic environment of patients with UC. KEY POINTS: • Effects of probiotics were evaluated using in vitro microbiota model of UC colon. • W. coagulans and lactate-utilizing butyrate producers have synergistic effects. • Co-inoculation of W. coagulans with A. caccae or C. butyricum enhanced butyrogenesis.

A burgeoning corpus of evidence indicates that S24-7 is integral to human health, with links to obesity, inflammation, metabolism, and dietary interactions. In the present study, we conducted a comprehensive review of the S24-7 literature from the past 10 years, augmented by an evaluation of research trends using both quantitative and qualitative approaches. From the Web of Science (WoS) database, we retrieved 903 research articles and four review articles pertaining to S24-7, also known as Muribaculaceae, that were published between January 1, 2014, and January 1, 2024. Employing software tools such as R, Biblioshiny, VOSviewer, the Bibliometric Analysis Platform, and Pajek, we performed visual mapping and correlation analyses on the collected documents. Our analysis revealed China and the United States as the leading publishers in the field of S24-7 research. The top three academic journals for S24-7 family research are Food and Function, Frontiers in Microbiology, and Nutrition. Among individual contributors, Zhang Y stands out with 31 publications and an h-index of 13, representing 3.42% of the 907 articles analyzed. Jiangnan University leads in institutional output with 46 publications. Keyword analysis underscores that S24-7 research is concentrated on examining the family's associations with obesity, inflammation, metabolism, and diet. This study highlights notable contributions from various countries, institutions, journals, and researchers, shedding light on the influence of the S24-7 family on human health. It serves to inform future research directions and clinical applications concerning the S24-7 flora.

This paper highlighted the structural changes of rice starch complexed with green tea catechin and lemon peel caffeic acid under thermomechanical-assist low moisture, and their prebiotics during in vitro digestibility and fermentation were further explained. Extruded starch with caffeic acid, characterized by enhanced short-range order, a distinct fractal structure, and a V-amylose helical arrangement, exhibited slower glucose release due to V-type inclusion crystalline structures and strong hydrogen bondings. Additionally, extruded starch with catechin or caffeic acid changed the composition of gut microbiota by increasing the proliferation of good bacteria and reducing pathogenic microorganisms, which led to a greater synthesis of short-chain fatty acids. According to a PICRUSt2 analysis, the extruded starch with caffeic acid may trigger metabolic alterations via altering the gut microbiota and increasing bile acid metabolism. Thus, extruded starch with caffeic acid demonstrates significant potential as a prebiotic for developing nutritionally tailored starch-based foods.

Immunosuppression often leads to drastic metabolic, hormonal, and physiological disorders. Changes in the gut microbiota are believed to be one of the factors contributing to these disorders, but the association remains uncertain. Clinical studies can be complicated by confounding variables, such as diet and other drivers of heterogeneity in human microbiomes. In this study, we identified pronounced gut microbiome signatures in rhesus macaques (RMs) with immunosuppression-induced lipid metabolism disorders following cyclosporine combined with dexamethasone. Furthermore, we observed similar changes in the gut microbiota of mice with immunosuppression-induced lipid metabolism disorders, which were associated with short-chain fatty acid metabolism. ELISA showed that immunosuppression significantly reduced the levels of butyric acid in both feces and serum of mice. Spearman correlation analysis identified a significant correlation between serum butyric acid levels and gut microbial dysbiosis induced by immunosuppression, particularly in relation to f_Lachnospiraceae, g_unidentified_Ruminococcaceae, and s_Clostridium leptum. Additionally, mice transplanted with gut microbiota from immunosuppressed mice exhibited hepatic lipid metabolism disorders, and RNA sequencing revealed significant downregulation of ABC transporters and PPARα in the liver, which was closely associated with lipid transport and metabolism, particularly Abca1. Moreover, butyric acid supplementation alleviated hepatic lipid metabolism disorders and upregulated the expression of Abca1 and PPARα in mice transplanted with immunosuppression-induced gut microbiota. Thus, we propose that the combination of cyclosporine and dexamethasone regulates the expression of hepatic Abca1 and PPARα by modulating the gut microbiota and its derived butyrate, particularly Lachnospiraceae and Clostridium leptum, further regulating hepatic lipid metabolism.

The thyroid gland is the body's largest single organ specialized for endocrine hormone production, and still unraveled mechanisms regulate its interaction between the hypothalamic-pituitary-thyroid axis and composition of the gut microbiota: in particular, a disrupted integrity of the intestinal barrier, causing dysbiosis and increasing detrimental substances or reducing beneficial metabolites, such as short-chain fatty acids (SCFAs) with proinflammatory effects, may be crucial for the induction of an autoimmune thyroid disease. More specifically, Lactobacilli and Bifidobacteria have a role in this partnership through a "molecular mimicry" mechanism, as their protein sequences share structural similarity with thyroid peroxidase and thyroglobulin. Lactobacilli can also increase T helper 17 cells, modifying the number of colonic regulatory T cells, largely implicated in the maintenance of immunological tolerance at the gut barrier. Additionally, Blautia and Anaerostipes work beneficially with butyric acid, one of the SCFAs, promoting antimicrobial peptide synthesis from the intestinal cells and bolstering the innate immune system's ability to struggle against pathogens, which can also influence thyroid hormone levels by regulating iodine uptake and metabolism. This review aims to summarize the current knowledge about the contribution of gut microbiota changes in triggering immune abnormalities leading to autoimmune thyroid diseases.

Laryngeal cancer incidence is rising globally; the role of gut microbiota remains underexplored. This study aimed to establish a causal link between gut microbiota and laryngeal cancer to inform preventive and therapeutic strategies.

Gut microbiota data from GWAS conducted by the MiBioGen consortium served as the exposure variable, with laryngeal cancer as the outcome variable. the exposure variable and the outcome variable were analyzed using Mendelian Randomization. The primary method was Inverse Variance Weighted analysis, with heterogeneity and pleiotropy assessed through Cochran's Q test, MR-Egger regression, and MR-PRESSO.

In the study, we identified five bacterial taxa with potential causal relationships with laryngeal cancer risk: Higher levels of Clostridiaceae1 (OR = 0.9993, 95% CI 0.9986-0.9999, p = 0.0463) and Turicibacter (OR = 0.9995, 95% CI 0.9989-0.9999, p = 0.0384) were linked to reduced cancer risk, while Mollicutes RF9 (OR = 1.0010, 95% CI 1.0003-1.0016, p = 0.0027), Euryarchaeota (OR = 1.0004, 95% CI 1.0001-1.0007, p = 0.0234), and Cyanobacteria (OR = 1.0005, 95% CI 1.0000-1.0009, p = 0.0464) were associated with increased risk.

Our findings suggest a causal relationship between gut microbiota composition and laryngeal cancer risk. Clostridiaceae1 and Turicibacter may play a protective role, while Mollicutes RF9, Euryarchaeota, and Cyanobacteria could contribute to increased cancer susceptibility. These insights highlight potential microbiome-based strategies for early detection, prevention, and therapeutic intervention in laryngeal cancer.

Level 5.

The COVID-19 pandemic has highlighted the need for a comprehensive understanding of the factors influencing disease severity and progression. Emerging research indicates that the human microbiota, particularly beneficial bacteria, significantly impacts immune responses and health outcomes in COVID-19 patients. While existing studies provide general insights into the relationship between the microbiota and probiotics with COVID-19, they often lack a detailed exploration of how specific bacterial taxa might be used as adjunctive treatments. This review aims to address this gap by focusing on ten key genera of beneficial bacteria, discussing their roles in COVID-19 and evaluating their potential as probiotics for prevention and treatment. The review covers the impact of these microbes on human health, their population alterations in COVID-19 patients, and their interactions with other viral infections. Among these microbes, several exhibit distinct patterns of abundance in COVID-19 patients, influencing disease outcomes and highlighting their potential roles in infection dynamics. In COVID-19 patients, populations of Akkermansia, Ruminococcus, and Roseburia are consistently reduced, while those of Faecalibacterium show a significant decline in more severe cases. Bacteroides presents varying effects depending on the species involved. Alterations in the abundance of Blautia and Lachnospiraceae are associated with increased inflammation and disease severity. Likewise, the depletion of Lachnospira and Coprococcus populations, both linked to anti-inflammatory effects, may exacerbate symptom severity. Oscillospira, though less studied, is connected to overall health and could have implications for viral infections. This review synthesizes the current understanding of these beneficial microbes to highlight the importance of maintaining a healthy microbiota to alleviate the impact of COVID-19 and contribute to the development of novel therapeutic strategies involving microbiota modulation.

Sarcopenia, an age-related disorder marked by decreased skeletal muscle mass, strength, and function, is associated with negative health impacts in individuals and financial burdens on families and society. Studies have suggested that age-related alterations in gut microbiota may contribute to the development of sarcopenia in older people through the gut-muscle axis, thus modulation of gut microbiota may be a promising approach for sarcopenia treatment. However, the characteristic gut microbiota for sarcopenia has not been consistent across studies. Therefore, the aim of this study was to compare the diversity and compositional differences in the gut microbiota of older people with and without sarcopenia, and to identify gut microbiota biomarkers with therapeutic potential for sarcopenia.

The PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database were searched studies about the gut microbiota characteristics in older people with sarcopenia. The quality of included articles was assessed by the Newcastle-Ottawa Scale (NOS). Weighted standardized mean differences (SMDs) and 95% confidence intervals (CIs) for α-diversity index were estimated using a random effects model. Qualitative synthesis was conducted for β-diversity and the correlation between gut microbiota and muscle parameters. The relative abundance of the gut microbiota was analyzed quantitatively and qualitatively, respectively.

Pooled estimates showed that α-diversity was significantly lower in older people with sarcopenia (SMD: -0.41, 95% CI: -0.57 to -0.26, I²: 71%, P < 0.00001). The findings of β-diversity varied across included studies. In addition, our study identified gut microbiota showing a potential and negative correlation with sarcopenia, such as Prevotella, Slackia, Agathobacter, Alloprevotella, Prevotella copri, Prevotellaceae sp., Bacteroides coprophilus, Mitsuokella multacida, Bacteroides massiliensis, Bacteroides coprocola Conversely, a potential and positive correlation was observed with opportunistic pathogens like Escherichia-Shigella, Eggerthella, Eggerthella lenta and Collinsella aerofaciens.

This study showed that α-diversity is decreased in sarcopenia, probably predominantly due to diminished richness rather than evenness. In addition, although findings of β-diversity varied across included studies, the overall trend toward a decrease in SCFAs-producing bacteria and an increase in conditionally pathogenic bacteria. This study provides new ideas for targeting the gut microbiota for the prevention and treatment of sarcopenia.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42024573090, identifier CRD42024573090.

Pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis. Induction and maintenance of remission is a crucial therapeutic goal. We investigated curcumin's efficacy in treatment of pouchitis.

The double-blind trial included an induction cohort of refractory pouchitis patients and a maintenance cohort of patients without pouchitis after IPAA. Patients received either placebo or curcumin for 8 weeks. The pouchitis activity were assessed before and after and was compared between cohorts or groups. Laboratory inflammation indicators, nutritional status and quality of life were also appraised.

52 patients were included, with 39 and 13 patients entering the maintenance cohort and induction cohort, respectively. In maintenance cohort, the proportion of clinical remission elevated from 11 to 89% in curcumin group (p = 0.005), whereas there was no significant difference in placebo group (10% vs 5%, p = 1).In induction cohort, 67% (4/6) patients achieved clinical response after 8 weeks' intervention of curcumin, whereas none treated with placebo (p = 0.021). Patients treated with curcumin appeared less inflammation and there was no significant difference in indicators changes between two cohorts.

Curcumin has preventive and therapeutic effects on pouchitis. Curcumin supplementation can reduce the disease activity and improve the nutritional status of patients with after IPAA.

ChiCTR, ChiCTR1900022243. Registered 31 March 2019, https://www.chictr.org.cn/historyversionpub.aspx?regno=ChiCTR1900022243.

The gut microbiome plays a crucial role in health and disease, influencing digestion, metabolism, and immune function. Traditional microbiome analysis methods are often expensive, time-consuming, and require specialized expertise, limiting their practical application in clinical settings. Evolving artificial intelligence (AI) technologies present opportunities for developing alternative methods. However, the lack of transparency in these technologies limits the ability of clinicians to incorporate AI-driven diagnostic tools into their healthcare systems. The aim of this study was to investigate an AI approach that rapidly predicts different bacterial genera and bacterial groups, specifically butyrate producers, from digital images of fecal smears of rhesus macaques (Macaca mulatta). In addition, to improve transparency, we employed explainability analysis to uncover the image features influencing the model's predictions.

By integrating fecal image data with corresponding metagenomic sequencing information, the deep learning (DL) and machine learning (ML) algorithms successfully predicted 16 individual bacterial genera (area under the curve (AUC) > 0.7) among the 50 most abundant genera in rhesus macaques (Macaca mulatta). The model was successful in predicting functional groups, major butyrate producers (AUC 0.75) and a mixed group including fermenters and short-chain fatty acid (SCFA) producers (AUC 0.81). For both models of butyrate producers and mixed fermenters, the explainability experiments revealed no decline in the AUC when random noise was added to the images. Increased blurring led to a gradual decline in the AUC. The model's performance was robust against the impact of fecal shape from smearing, with a stable AUC maintained until patch 4 for all groups, as assessed through scrambling. No significant correlation was detected between the prediction probabilities and the total fecal weight used in the smear; r = 0.30 ± 0.3 (p > 0.1) and r = 0.04 ± 0.36 (p > 0.8) for the butyrate producers and mixed fermenters, respectively.

Our approach demonstrated the ability to predict a wide range of clinically relevant microbial genera and microbial groups in the gut microbiome based on digital images from a fecal smear. The models proved to be robust to the smearing method, random noise and the amount of fecal matter. This study introduces a rapid, non-invasive, and cost-effective method for microbiome profiling, with potential applications in veterinary diagnostics.

Avian pathogenic Escherichia coli (APEC) threatens both poultry production and human health. Xylooligosaccharides (XOS) may suppress pathogenic bacteria through prebiotic actions. However, the influences of single degree of polymerization (DP) on the inhibition of APEC by XOS remain unknown. This study aimed to probe if XOS and their major monomers (xylobiose, xylotriose and xylotetraose) could differentially combat APEC via prebiotic actions using an in vitro fermentation model with chicken cecal microbiota.

Microbiota were randomly divided into 7 groups (5 replicate tubes/group). Control group (CON) received no treatment; XOS group received commercial XOS mixtures; APEC group received APEC; XA, X2, X3 and X4 groups received APEC combined with commercial XOS mixtures, xylobiose, xylotriose and xylotetraose, respectively.

XOS and their major monomers mitigated APEC-induced decline (p < 0.05) in gut microbial α-diversity, with xylotetrose showing the least effect. Gut microbiota in XA, X2, X3 and X4 groups clustered together, with a relative separation observed in X4 group. XOS and their monomers elevated (p < 0.05) the abundances of Firmicutes, Bacteroidota and several probiotics (Lactobacillus, Bacteroides and Megamonas), but reduced (p < 0.05) the abundances of Proteobacteria and Escherichia-Shigella, with xylotetraose exhibiting the least efficacy. Besides, xylotriose and xylotetrose had an advantage over xylotetraose in promoting microbial production of short-chain fatty acids. Metabolomics analysis revealed that APEC challenge mainly downregulated (p < 0.05) several amino acids metabolism pathways of gut microbiota, while xylotriose had an inferiority to XOS in upregulating (p < 0.05) histidine metabolism pathway. Furthermore, microbial fermentation metabolites of all XOS monomers lowered (p < 0.05) certain virulence genes expression in APEC, with xylotriose being the most advantageous.

XOS and their major monomers differentially improved gut microbiota and metabolite profiles in chicken gut against APEC challenge. Overall, xylotriose exhibited the greatest inhibition against APEC abundance and virulence. Our findings underscore the role of single DP in influencing the prebiotic actions of XOS against APEC, providing a basis for the reasonable application of XOS in diets to combat bacterial challenge.

Nonalcoholic Steatohepatitis (NASH) is a progressive liver disease characterized by inflammation and liver damage. Allicin, a bioactive compound derived from garlic, has demonstrated anti-inflammatory and antioxidant properties. This study explores the effects of allicin on NASH and gut microbiota dysbiosis induced by a high-fat, high-fructose diet (HFFD) in mice. Allicin supplementation significantly alleviated hepatic inflammation, improved glucose metabolism, and modulated the circadian rhythm gene Rev-erbα, which plays a critical role in regulating inflammation. The anti-inflammatory effects of allicin were diminished in Si-Rev-erbα-treated HepG2 cells, highlighting the importance of circadian regulation in mediating these effects. Allicin's anti-inflammatory effects were associated with increased levels of short-chain fatty acids (SCFAs) and the restoration of diurnal oscillations in proinflammatory cytokines and gut microbiota composition, particularly in genera, such as Akkermansia, Bacteroidetes, and Lactobacillus. These findings suggest that allicin could be a promising therapeutic approach for managing NASH, liver dysfunction, and related metabolic disorders through the modulation of circadian rhythms and the gut microbiome.

Metabolomics describes the metabolic profile of an organism at a given time by the concentrations of its constituent metabolites. When studied over time, metabolite concentrations can help understand the dynamical evolution of a biological process. However, metabolites are involved into sequences of chemical reactions, called metabolic pathways, related to a given biological function. Accounting for these pathways into statistical methods for metabolomic data is thus a relevant way to directly express results in terms of biological functions and to increase their interpretability.

We propose a new method, phoenics, to perform differential analysis for longitudinal metabolomic data at the pathway level. In short, phoenics proceeds in two steps: First, the matrix of metabolite quantifications is transformed by a dimension reduction approach accounting for pathway information. Then, a mixed linear model is fitted on the transformed data.

This method was applied to semi-synthetic NMR data and two real NMR datasets assessing the effects of antibiotics and irritable bowel syndrome on feces. Results showed that phoenics properly controls the Type I error rate and has a better ability to detect differential metabolic pathways and to extract new impacted biological functions than alternative methods. The method is implemented in the R package phoenics available on CRAN.

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, type 2 diabetes mellitus, 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, 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, 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.

Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease (KD) an acute pediatric vasculitis, remains unclear.

We used the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to assess the contribution of the intestinal microbiota to the development of vascular inflammation. We evaluated the severity of vasculitis in microbiota-depleted mice. 16S rRNA gene sequencing was used to characterize the fecal microbiome composition of LCWE-injected mice. Some groups of mice were orally treated with selected live or pasteurized bacteria, short-chain fatty acids, or Amuc_1100, the Toll-like receptor 2 signaling outer membrane protein from Akkermansia muciniphila, and their impact on vasculitis development was assessed.

We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking KD vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Oral supplementation with either of these live or pasteurized individual bacteria or with short-chain fatty acids produced by them attenuated cardiovascular inflammation, as reflected by decreased local immune cell infiltrations. Treatment with Amuc_1100 also reduced the severity of vascular inflammation.

This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in KD vasculitis pathogenesis and identifies specific intestinal commensals that regulate vasculitis in mice by producing metabolites or via extracellular proteins capable of enhancing and supporting gut barrier function.

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

Delayed neutrophil recovery during acute lymphoblastic leukemia (ALL) treatment increases the risk of infection and causes delay in chemotherapy. Emerging evidence implicates gut microbiota in neutrophil reconstitution after chemotherapy. We explored the interplay between the gut microbiota and neutrophil dynamics, including neutrophil chemoattractants, in 51 children with newly diagnosed ALL. Daily absolute neutrophil count (ANC), weekly plasma chemokines (CXCL1 and CXCL8), granulocyte colony-stimulating factor (G-CSF), and fecal samples were monitored until day 29 during ALL induction treatment. Fecal sequencing using 16S ribosomal RNA revealed an overall significant reduction in bacterial diversity and Enterococcus overgrowth throughout the induction treatment. Prolonged neutropenia (ANC <0.5 × 109 cells per L at day 36) and elevated chemokine levels were associated with a decreased abundance of genera from the Ruminococcaceae and Lachnospiraceae families, decreased Veillonella genus, and Enterococcus overgrowth from diagnosis and throughout induction treatment. G-CSF was upregulated in response to neutropenia but was unrelated to microbiota changes. Overall, this study revealed that a diminished abundance of specific intestinal commensals and Enterococcus overgrowth is associated with delayed neutrophil reconstitution and increased chemokine signaling, indicating that disruption of the microbiota may contribute to prolonged neutropenia. These findings lay the groundwork for future investigations into the mechanisms underlying these associations and their clinical implications for developing gut-sparring strategies to minimize the impact of gut dysbiosis on immune recovery.

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.

Ecological resilience is the capacity of an ecosystem to maintain its state and recover from disturbances. This concept can be applied to the gut microbiome as a marker of health.

Several metrics have been proposed to quantify microbiome resilience, based on the prior choice of some salient feature of the trajectories of microbiome change. We propose a data-driven approach based on compositional and functional data analysis to quantify microbiome resilience. We demonstrate the validity of our approach through applications to sled dogs undergoing three types of exercise: running on an exercise wheel, pulling an all-terrain vehicle, and pulling a sled.

Microbiota composition was clearly impacted by each exercise type. Log-ratio analysis was utilized for dimensionality reduction and identified 33 variables (taxa) explaining 90% of the variance. Functional principal component analysis identified two scores (FPCA 1 and FPCA2) which explained 76% and 19% of the variability of the trajectories, respectively. More resilient trajectories corresponded to low values of FPCA1 and FPCA2 values close to zero. Levels of chemokines MCP-1 and KC-like, which increased significantly after exercise and returned to pre-exercise levels within 24 h, were significantly associated with FPCA scores as well.

To our knowledge, this is the first study proposing a principled approach to quantify microbiome resilience in healthy dogs and associate it with immune response to exercise-related stress.

Alzheimer's disease (AD) is a cognitive disease with high morbidity and mortality. In AD patients, the diversity of the gut microbiota is altered, which influences pathology through the gut-brain axis. Probiotic therapy alleviates pathological and psychological consequences by restoring the diversity of the gut microbial flora. This study addresses the role of altered gut microbiota in the progression of neuroinflammation, which is a major hallmark of AD. This process begins with the activation of glial cells, leading to the release of proinflammatory cytokines and the modulation of cholinergic anti-inflammatory pathways. Short-chain fatty acids, which are bacterial metabolites, provide neuroprotective effects and maintain blood‒brain barrier integrity. Furthermore, the gut microbiota stimulates oxidative stress and mitochondrial dysfunction, which promote AD progression. The signaling pathways involved in gut dysbiosis-mediated neuroinflammation-mediated promotion of AD include cGAS-STING, C/EBPβ/AEP, RAGE, TLR4 Myd88, and the NLRP3 inflammasome. Preclinical studies have shown that natural extracts such as Ganmaidazao extract, isoorentin, camelia oil, Sparassis crispa-1, and xanthocerasides improve gut health and can delay the worsening of AD. Clinical studies using probiotics such as Bifidobacterium spp., yeast beta-glucan, and drugs such as sodium oligomannate and rifaximine have shown improvements in gut health, resulting in the amelioration of AD symptoms. This study incorporates the most current research on the pathophysiology of AD involving the gut microbiota and highlights the knowledge gaps that need to be filled to develop potent therapeutics against AD.

Rheumatoid arthritis (RA) is a prevalent chronic autoimmune disease characterized by symmetric polyarthritis, resulting in pain and swelling in the synovial joints. Flemingia philippinensis, a traditional Chinese medicine, has been shown to be an effective treatment approach for anti-rheumatoid arthritis (RA), which still needs further research in its active ingredient and regulatory mechanisms.

This study aimed at investigate the pharmacodynamic basis and intricate mechanism of action of Flemingia philippinensis (FPTF) in the treatment of RA based on integrated omics technologies.

UPLC-Q-Orbitrap HRMS was first established to identify the active components of FPTF in blood and network pharmacology was then used to predict the key therapeutic targets and corresponding pathways of FPTF in treatment of RA. To substantiate the pharmacodynamic effects, a collagen-induced arthritis (CIA) animal model was employed to observe the anti-RA effects of FPTF through a series of indicators, including rat body weight, arthritis scoring, paw swelling, histopathological analysis of synovial tissue, and serum inflammatory factors. Subsequently, the potential mechanisms underlying the anti-RA efficacy of FPTF was elucidated by integrating metabolomics analysis with 16S rRNA gene sequencing. Specifically, the RT-qPCR experiment was further conducted to validate the pathways predicted by serum pharmacochemistry, network pharmacology, metabolomics and 16S rRNA gene sequencing.

A total of 10 compounds derived from FPTF were identified by serum sample analysis. Utilizing network pharmacology, we identified 117 common targets for FPTF in the treatment of RA. Notably, KEGG analysis highlighted the PI3K/AKT signaling pathway and the IL17 signaling pathway as key pathways associated with the anti-RA effects of FPTF. Pharmacodynamic studies showed that FPTF can significantly alleviate CIA-induced arthritis. Compared with the CIA model group, FPTF treatment significantly improved the expression of mRNA in the PI3K/AKT and IL-17 signaling pathways. Further investigation unveiled a total of 28 differential metabolites in serum samples, among which 21 metabolites were observed to be reversed following FPTF administration. Metabolomic profiling revealed pronounced perturbations in amino acid metabolism, fatty acid metabolism, and glycerophospholipid metabolism pathways in CIA rats, which were partially rectified by FPTF treatment. Additionally, 16S rRNA gene sequencing analysis indicated that FPTF could restore the gut microbiota balance disrupted by RA. RT-qPCR further confirmed that FPTF can modulate key enzymes in metabolic pathway analysis and gut microbiota metabolic pathways.

This study pioneeringly elucidates the potential pharmacodynamic material basis of FPTF for treatment of RA, detailing the regulated metabolic pathways and key gut microbiota genera involved. The findings provide a comprehensive understanding of mechanisms underlying the effects of FPTF in RA treatment.

Perioperative neurocognitive disorders (PND) refer to a constellation of symptoms that primarily affect the elderly and typically manifest as common complications after exposure to surgery and anesthesia. PND is associated with high morbidity, mortality, and progression to neurodegenerative diseases, thus exerting significant financial strains on families as well as the healthcare system. Given that an ageing global population is an inevitable trend and, with the latest advances in the healthcare system, an ever-growing number of elderly people present for surgery and anesthesia, PND is of prominent concern. The two-way communication between the intestinal flora and the brain, also known as the microbiota-gut-brain axis, plays an important role in central nervous system development, and multiple studies have highlighted the influence exerted by gut microbiome in both health and disease. Pertinent studies have corroborated the fact that anesthesia and surgery disrupt the harmony of the gut ecology, which sets off a cascade of events that initiate neuroinflammation, eventually leading to PND. Probiotics, which are live microorganisms that promote the host's health, have been shown as a viable option to restore or minimise the disruption of gut flora. Evidence exists that probiotics exhibit immunomodulatory and anti-inflammatory benefits. Given the effectiveness of probiotics in reducing neuroinflammation, research has also focused on their impact on the development of PND. This review aims to compile the data from relevant clinical trials focusing on the influence of probiotics on PND to determine whether the derived findings might be applied for the prevention and treatment of PND.

Lifestyle interventions, such as diet and exercise, are currently the main therapies against metabolic dysfunction-associated steatotic liver disease (MASLD). However, not much is known about the combined impact of fiber and exercise on the modulation of gut-liver axis and MASLD amelioration. Here, we studied the impact of the combination of exercise training and a fiber-rich diet on the amelioration of MASLD. Male APOE*3-Leiden.CETP mice were fed a high-fat high-cholesterol diet with or without the addition of fiber (10% inulin) and exercise trained on a treadmill, or remained sedentary. Exercise training and fiber supplementation reduced fat mass gain and lowered plasma glucose levels. Only the combination treatment, however, induced fat loss and decreased plasma triglyceride and cholesterol levels compared with sedentary control mice. Exercise training with and without the addition of fiber had a similar ameliorating effect on the MASLD score. Only exercise without fiber decreased the hepatic expression of inflammatory markers. Fiber diet was mainly responsible for remodeling the gut microbial composition, with an increase in the relative abundance of the short-chain fatty acid (SCFA)-producing genera Anaerostipes and Muribaculaceae, whereas, surprisingly, exercise training alone and with fiber resulted in the highest increase of SCFA production. Overall, the combination of exercise training and dietary fiber decreases fat mass and improves glucose and lipid homeostasis but does not have an additional synergistic positive effect on liver health compared with exercise training alone.NEW & NOTEWORTHY The combination of dietary fiber intake and exercise training has a synergetic beneficial effect on the metabolic health, resulting in fat loss, lowered blood glucose, and lowered plasma lipid levels in mice with steatotic liver disease. However, fiber supplementation, despite a positive remodulation of the gut-liver axis, does not have an additional positive effect on liver health compared with exercise training alone.