The gut microbiome produces short-chain fatty acids (SCFAs), which serve as a substantial energy source and provide a link between the microbiome and (cardiac) metabolism. It has been demonstrated that the composition of the microbiome is altered in patients with heart failure (HF), but whether circulating levels of SCFAs are altered in HF is unknown.

Serum concentrations of the SCFAs acetate, propionate, and butyrate were measured in 205 patients with HF and in 54 healthy controls, using isotope dilution liquid chromatography-tandem mass spectrometry. Of the patients with HF, 99 had HF with a reduced ejection fraction (HFrEF) and 106 had HF with mildly-reduced or preserved ejection fraction (HFmrEF/HFpEF). Healthy controls were age and sex matched to the HFrEF patients. Serum concentrations of acetate and propionate were significantly lower in patients with HF than in healthy controls, whereas butyrate levels were higher in patients with HF. Analyses by HF type revealed that acetate and propionate levels were lower in both HFrEF and HFpEF/HFmrEF patients in comparison to healthy controls. However, butyrate levels were observed to be lower in patients with HFmrEF/HFpEF in comparison to healthy controls, while they were higher in patients with HFrEF.

In patients with HF, serum levels of acetate and propionate are lower across the HF spectrum, whereas serum butyrate levels are elevated in HFrEF, but lower in HFmrEF/HFpEF. These alterations in SCFA profiles suggest a microbiome-driven metabolic dysregulation, which appears to differ between HF subtypes.

The aim of this study was to investigate the structure, physicochemical properties, and changes in vitro digestion and fermentation between unfermented tea residue dietary fiber (UDF) and fermented tea residue soluble dietary fiber (FSDF). The results showed that soluble dietary fiber in FSDF was increased from 2.54 % to 15.65 % after fermentation modification. Monosaccharide composition analysis showed that xylose and glucose accounted for a higher proportion in FSDF. FSDF had smaller particle size, lower crystallinity and higher thermal stability. The water holding capacity, oil holding capacity and water swelling capacity of FSDF were significantly increased. Rheological properties showed that FSDF exhibited higher viscosity and better elastic than UDF. Furthermore, FSDF generated more short-chain fatty acids, and the structure was looser than UDF, which was easier to be utilized by intestinal flora. These findings provided higher value of dietary fiber in tea residue by fermentation modification as functional products.

Parkinson's disease (PD) is characterized by the aggregation of α-synuclein (α-syn) and the loss of dopaminergic (DA) neurons, with growing evidence suggesting a significant role of gut microbiota and their metabolites in the disease's pathogenesis. This study explores the effects of short-chain fatty acids (SCFAs) on PD progression, focusing on the G protein-coupled receptor 43 (GPR43) and the NLRP3 signaling pathway in both in vitro and in vivo models. Employing the1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model and SH-SY5Y cells with SCFAs-treated, this study investigated the impact of SCFAs on α-syn deposition, DA loss, and neuroinflammation. In vitro, supernatant from STC-1 cells was administered to SH-SY5Y cells, and the effects were assessed following the knockdown of NLRP3 or GPR43. In vivo, mice were treated with NLRP3 or GPR43 inhibitors after feeding with SCFAs, and the motor deficits, α-syn pathology, DA neuronal loss, and inflammatory responses were observed. SCFAs were found to exacerbate motor and gastrointestinal dysfunctions in PD models, intensifying α-syn pathology and neuroinflammation. The activation of the NLRP3 inflammasome through GPR43 emerged as a key pathological mechanism, with inhibition of these molecules mitigating the observed effects. Such interventions reduced α-syn accumulation, DA loss, and inflammatory responses, highlighting the pivotal role of the SCFA/GPR43-NLRP3 pathway in PD. The findings from this study elucidate a critical link between gut-derived metabolic changes and neuroinflammatory processes in PD via the SCFA/GPR43-NLRP3 pathway. Targeting this pathway offers a promising therapeutic strategy and enriches our understanding of the gut-brain axis' role in PD progression.

In this study, maltotriosyl-erythritol (EG3) was synthesized as a novel prebiotic candidate via transglycosylation using recombinant amylomaltase (AMase) from Thermus sp. Tapioca starch served as the glucosyl donor, and erythritol as the acceptor. High-performance liquid chromatography (HPLC) revealed an EG3 yield of 14.0 % with a concentration of 2.8 mg/mL. Mass spectrometry confirmed the molecular weight of EG3 as 608 Da, and its strucopture was verified by 1H and 13C NMR analysis. EG3 exhibited greater resistance to acid, heat, and digestive enzymes compared to erythritol glucosides (EG1-2) and significantly promoted the growth of Lactobacillus casei BCC36987. Fermentation of EG3 resulted in the highest levels of lactic acid and total short-chain fatty acids, which may contribute to reduced pH levels. These findings suggest that erythritol-receptor products formed via AMase-catalyzed reactions, particularly EG3, are promising prebiotic ingredients, with the prebiotic activity of erythritol derivatives being influenced by the length of the carbohydrate chain.

Silicosis is a pulmonary disease characterized by inflammation and progressive fibrosis. Previous studies have shown that polydatin (PD) has potential biological activity in key signaling pathways regulating inflammation and apoptosis. To investigate the effect of PD on rats with silicosis, this study used network pharmacology and molecular docking methods to determine the target of PD treatment for silicosis. The therapeutic effect of PD on silicosis was confirmed by measuring the lung injury score, hydroxyproline content, and mRNA expression levels of key targets. In addition, metagenomic sequencing and gas chromatography-mass spectrometry were used to determine the gut microbiota composition and targeted metabolomics analysis, respectively. The results showed that PD could inhibit the expression of inflammation-related indexes and apoptosis-related indexes at protein and mRNA levels. PD also regulates the diversity of the intestinal flora and the content of short-chain fatty acids. In conclusion, the current data suggest that PD has a protective effect against silica-induced lung injury and plays a protective role in regulating intestinal flora diversity and short-chain fatty acid levels through the gut-lung axis.

Probiotics have been increasingly recognized for positively influencing many aspects of human health. Lactiplantibacillus plantarum (L. plantarum), a non-pathogenic bacterium, previously known as Lactobacillus plantarum, is one of the lactic acid bacteria commonly used in fermentation. The probiotic properties of L. plantarum have highlighted its health benefits to humans when consumed in adequate amounts. L. plantarum strains primarily enter the body orally and alter intestinal microflora and modulate the immune responses in their host; thereby benefiting human health. Furthermore, the use of L. plantarum as vaccine vectors delivering mucosal antigens has been shown to be a promising strategy. These aspects, from Immunomodulation to vaccine delivery by L. plantarum in preclinical settings, are highlighted in this review. Along these lines, construction of a recombinant L. plantarum strain expressing a B cell multi-peptide, as a future vaccine to modulate immunity and confer anti-tumor effect by targeting Her-2/neu-overexpressing cancers in local and distal sites, is also presented and discussed.

Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation in the gastrointestinal tract, and is usually accompanied by dysbiosis in the gut microbiome, a factor that contributes to disease progression. Excessive production of reactive oxygen species (ROS) because of gut microbiome dysbiosis-one of the hallmark features of IBD-promotes chronic inflammation and facilitates the transformation of normal cells into senescent cells. Cellular senescence is associated with the development of various chronic and age-related diseases. We hypothesise that senolytic agents, specifically dasatinib (D) and quercetin (Q), could have a beneficial effect on both the gut microbiome and intestinal cells in IBD. The modulatory effects of a combination of D + Q was assessed in the M-SHIME model with faecal microbiota sourced from Crohn's disease patients. D + Q significantly modulated butyrate and lactate levels in the samples from specific patients. In addition, metabolomic analysis showed that D + Q positively impacted the abundance of anti-inflammatory bacteria while also significantly reducing the several species of pathogenic bacteria. Findings from a Caco-2 cell/THP1 co-culture model of IBD demonstrated that D + Q exerted strong immunomodulatory effects on the gut epithelium, evidenced by reduced NF-kB activity, and lower levels of the pro-inflammatory markers TNF-α, CXCL-10, and MCP-1. Furthermore, D + Q induced the secretion of anti-inflammatory cytokines, including IL-6 and IL-10. However, it should be noted that D + Q also led to the secretion of the pro-inflammatory cytokines IL-8. These findings suggest that D + Q could offer a novel therapeutic approach for advanced IBD management by modulating both the gut microbiome and inflammatory pathways. The results support the potential repurposing of senotherapeutic agents as a strategy for addressing the chronic inflammation central to IBD pathogenesis.

Diabetic kidney disease is the main cause of end-stage renal disease, and its prevention and treatment are still a major clinical problem. The human intestine has a complex flora of hundreds of millions of microorganisms, and intestinal microorganisms, and their derivatives are closely related to renal inflammatory response, immune response, and material metabolism. Brown adipose tissue is the main part of adaptive thermogenesis. Recent studies have shown that activating brown fat by regulating intestinal flora has good curative effects in diabetic kidney disease-related diseases. As an emerging medical concept, the "gut-fat-kidney" axis has received increasing attention in diabetic kidney disease and related diseases. However, the specific mechanism involved needs further study. A new theoretical basis for the prevention and treatment of diabetic kidney disease is presented in this article, based on the "gut-fat-kidney" axis.

Chronic diarrhea (CD), a common chronic condition resulting from various mechanisms, has chronic inflammation as a primary determinant. Despite recent research exploring the potential mechanisms linking lipids and diarrhea, clinical studies on the relationship between lipids and the onset of CD are limited. This study aimed to investigate the association between the atherogenic index of plasma (AIP) and CD risk.

This cross-sectional study used data from the 2005-2010 NHANES. The association between AIP and CD was examined through multiple linear regression analyses. A smooth curve-fitting algorithm was applied to assess the potential non-linear dose-response relationship between AIP and CD, and subgroup analyses were conducted.

Among 5,948 participants, 440 (7.4%) had CD. After adjusting for potential confounders, AIP was significantly associated with CD (OR, 1.57; 95% CI, 1.08-2.30; P = 0.018). The highest AIP quartile (Q4; 0.18 to 0.92) showed an adjusted OR for CD of 1.51 (95% CI, 1.10-2.07; P = 0.011) versus the lowest quartile (Q1; -1.15 to -0.25). Subgroup analyses indicated that diabetic individuals with higher AIP had a higher CD risk (OR, 3.84; 95% CI, 1.45-10.15), with an observed additive interaction (P for interaction = 0.045).

This study demonstrates a significant association between AIP and CD risk. AIP may serve as a promising indicator for assessing CD risk, offering valuable insights for prevention and treatment strategies.

Chronic obstructive pulmonary disease (COPD) is a global health challenge with the high morbidity and mortality. Cordyceps militaris (CM) is a medicinal fungus that has been widely used in Asia for centuries. It has the effects of tonifying the lung and kidney, replenishing essence, resolving phlegm, and stopping bleeding. CM has been used clinically for alleviating COPD in China. However, the potential mechanism of CM in treating COPD remains indistinct.

This article aimed to evaluate the efficacy and investigate the underlying mechanism of CM in treatment of COPD.

The ingredients in CM were identified by LC Q/TOF-MS. The effect of CM in COPD was evaluated. Untargeted metabolomics assay and 16S rDNA sequencing were employed to examine the changes in metabolites and gut microbiota in COPD mice. Gut microbiota ablation experiment and quantification of short chain fatty acids (SCFAs) were integrated to elucidate the systematic mechanism of CM in treatment of COPD.

A total of 22 ingredients were identified in CM. CM alleviated COPD significantly by improving lung function and inhibiting pulmonary inflammation. Subsequently, 11 differential metabolites regulated by CM were mainly associated with amino acid metabolism. CM ameliorated the dysbiosis of intestinal microbiota in COPD mice, which contributed to the treatment of COPD. Moreover, CM increased the contents of SCFAs, including acetate, propionate, butyrate and isobutyrate. Spearman correlation indicated a close relationship among pulmonary function, differential metabolites, and gut microbiota.

This study revealed that CM alleviated COPD by regulating amino acid metabolism, ameliorating the imbalance of gut microbiota and increasing the SCFAs. These findings not only establish a foundation for the research of CM but also provide a basis for new treatment strategies of COPD.

To investigate the causal relationships between gut microbiota and novel adult-onset type 2 diabetes mellitus(T2DM) subtypes.

We conducted Mendelian randomization (MR) analyses using genome-wide association data from European populations. Initial MR analyses examined associations between gut microbiota and four T2DM subtypes, followed by validation analyses using type 1 diabetes mellitus(T1DM) and T2DM GWAS data. We also performed bidirectional MR analyses and tested for heterogeneity and pleiotropy across all analyses.

Our MR analyses revealed distinctive associations between gut microbiota and T2DM subtypes: six bacterial taxa with severe insulin-deficient diabetes (SIDD), four with severe insulin-resistant diabetes (SIRD), eight with mild obesity-related diabetes (MOD), and eight with mild age-related diabetes (MARD). These associations were distinct from T1DM findings. Six bacterial taxa were validated in T2DM analyses, with four showing directionally consistent effects: Class Clostridia (OR = 0.57, P = 0.045) and Order Clostridiales (OR = 0.57, P = 0.045) were associated with reduced MOD risk, while species Catus (OR = 1.80, P = 0.007) was associated with increased MOD risk, and genus Holdemania (OR = 2.51, P = 0.004) was associated with increased SIRD risk. No significant heterogeneity or pleiotropy was observed across analyses.

Our MR analyses reveal novel causal relationships between gut microbiota and adult-onset T2DM subtypes, though further validation studies are warranted.

Identifying potential connections between microbe-drug pairs play an important role in drug discovery and clinical treatment.Techniques like graph neural networks effectively derive accurate node representations from sparse topologies,however, they struggle with over-smoothing and over-compression, and their interpretability is relatively poor.Conversely, mathematical methods with low-rank approximations are interpretable but often get trapped in local optima.To address these issues, we propose a new prediction model named NNSFMDA,in which, the bounded nuclear norm minimization and the simplified transformer were combined to infer possible drug-microbe associations. In NNSFMDA, we first constructed a heterogeneous microbe-drug network by integrating multiple microbe and drug similarity metrics,according to which, we subsequently transformed the prediction problem to a matrix filling problem, and then, iteratively approximated the matrix by minimizing the number of bounded nuclear norm. Finally, based on the newly-filled matrix, we introduced a simplified transformer to estimate possible scores of microbe-drug pairs. Results showed that NNSFMDA could achieve reliable AUC value of 0.98, Which outperformed existing state-of-the-art competitive methods. In the experimental section, ablation experiments and modular analyses further demonstrate the superiority of the model, and case studies of microbe-drug associations confirm the validity of the model. These tests have all highlighted the potential of the NNSFMDA to predict latent microbe-drug associations in the future.

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition linked to gut microbiota dysbiosis and altered production of bacterial metabolites, including succinate, which is also a key intermediate in human mitochondrial energy metabolism in human cells. Succinate levels in the gut are influenced by microbial community dynamics and cross-feeding interactions, highlighting its dual metabolic and ecological importance. Extracellular succinate acts as a key signaling metabolite linking microbial metabolism to host physiology, with transient rises supporting metabolic regulation but chronic elevations contributing to metabolic disorders and disease progression. Succinate signals through its cognate receptor SUCNR1, which mediates adaptive metabolic responses under normal conditions but drives inflammation and fibrosis when dysregulated. IBD patients display a dysbiotic gut microbiota characterized by an increased prevalence of succinate-producing bacteria, contributing to elevated succinate levels in the gut and circulation. This imbalance drives inflammation, worsens IBD severity, and contributes to complications like Clostridioides difficile infection and fibrosis. Emerging evidence highlights the potential of intestinal and systemic succinate levels as indicators of microbial dysbiosis, with a bidirectional relationship between microbial composition and succinate metabolism. Understanding the factors influencing succinate levels and their interaction with dysbiosis shows promise in the development of therapeutic strategies to restore microbial balance. Approaches such as dietary fiber enrichment, prebiotics, and probiotics to enhance succinate-consuming bacteria, combined with targeted modulation of succinate pathways (e.g. SDH inhibitors, SUCNR1 antagonists), hold promise for mitigating inflammation and improving gut health in IBD.

Exposure to arsenic causes health problems and is associated with adverse effects on fertility and development. Humans are facing increasing exposure to arsenic from multiple sources, such as drinking water, food products, and industrial processes. The mechanisms behind arsenic-induced reproductive toxicity and its impact on fertility and the development of future generations are investigated by the protective role of metformin (200 mg/kg) against arsenic-induced (20 ppm As2O3) ovarian damage in both maternal and offspring generations. Results showed arsenic exposure caused significant weight loss, increased mortality, reduced serum anti-Mullerian hormone (AMH) levels, and heightened oxidative stress, indicated by increased reactive oxygen species (ROS), malondialdehyde (MDA), and reduced ovarian antioxidant activity. Gene expression changes related to apoptosis and inflammation, such as BAX, Bcl-2, Bcl-2, caspase-3, tumor necrosis factor-alpha (TNF-α), and interleukin-1 (IL-1), were also noted, along with a decrease in HO-1 expression. Arsenic exposure led to a reduction in ovarian follicles and an increase in atretic follicles and uterine thickness. However, metformin significantly reduced ROS and MDA levels, enhanced antioxidant capacity, and protected ovarian tissue by upregulating heme oxygenase-1 (HO-1) and Bcl-2, modulating apoptotic and inflammatory genes, and preserving AMH levels. The possible protective role of metformin against arsenic-induced toxicity and its detrimental effects aims to improve therapeutic approaches to alleviate the harmful consequences of environmental pollutants, especially arsenic.

Bacteriophage therapy is a promising approach for targeting antibiotic-resistant bacteria and modulating gut microbiota in metabolic diseases such as obesity. This study evaluated the impact of a two-phage cocktail on an ex vivo colonic simulation model of gut microbiota derived from obese individuals, both in its normalized state and after enrichment with Enterobacter cloacae, an obesity-related bacteria. Microbiological analyses confirmed that the phage cocktail remained active throughout the colonic regions over three digestion cycles and effectively reduced enterobacterial populations in the enriched microbiota. Metabarcoding of the 16S rRNA gene revealed that phage therapy did not significantly alter the abundance of dominant genera, but selectively reduced E. cloacae across all colonic regions. Alpha diversity was significantly affected only in the enriched microbiota, while beta diversity analysis indicated significant compositional shifts during therapy, with reduced dispersion in the final treatment stage. Short-chain fatty acid profiling demonstrated region- and group-specific metabolic responses, with increased lactic and butyric acid concentrations in the ascending colon of the enriched microbiota following phage treatment. This study provides the first ex vivo evidence that a two-phage cocktail can selectively eliminate E. cloacae while preserving overall microbiota structure and functionality. These findings establish a foundation for future in vivo studies exploring the role of phage therapy in reshaping gut microbial communities and metabolic profiles, highlighting its potential as a precision tool for managing gut dysbiosis in metabolic disorders.

Acute respiratory distress syndrome (ARDS) survivors often suffer from long-term psychiatric disorders such as depression, but the underlying mechanisms remain unclear. Here, we found marked alterations in the composition of gut microbiota in both ARDS patients and mouse models. We investigated the role of one of the dramatically changed bacteria-Akkermansia muciniphila (AKK), whose abundance was negatively correlated with depression phenotypes in both ARDS patients and ARDS mouse models. Specifically, while fecal transplantation from ARDS patients into naive mice led to depressive-like behaviors, microglial activation, and intestinal barrier destruction, colonization of AKK or oral administration of its metabolite-propionic acid-alleviated these deficits in ARDS mice. Mechanistically, AKK and propionic acid decreased microglial activation and neuronal inflammation through inhibiting the Toll-like receptor 4/nuclear factor κB signaling pathway. Together, these results reveal a microbiota-dependent mechanism for ARDS-related depression and provide insight for developing a novel preventative strategy for ARDS-related psychiatric symptoms.

Chlorella vulgaris is a source of potential bioactive compounds that can reach the large intestine and interact with colonic microbiota. However, the effects of consumption of this microalga on gastrointestinal function have scarcely been studied. This paper simulates, for the first time, the passage of C. vulgaris through the gastrointestinal tract, combining the INFOGEST method and in vitro colonic fermentation to evaluate potential effects on the human colonic microbiota composition by 16S rRNA gene sequencing and its metabolic functionality. The results show that the presence of this microalga increased the release of short-chain fatty acids (SCFAs), such as acetic, propionic, butyric, and isobutyric fatty acids, after 48 h colonic fermentation, being indicators of gut health. In correlation with the release of SCFAs, a significant reduction in bacterial groups causing intestinal imbalance, such as Enterobacteriaceae, Enterococcus spp., and Staphylococcus spp., was observed. In addition, digests from C. vulgaris favored intestinal health-related taxa, such as Akkermansia and Lactobacillus. C. vulgaris is, therefore, a promising food ingredient for good intestinal health and the maintenance of a balanced colonic microbiota.

Cardiovascular diseases are a leading cause of death worldwide, and the process of cardiac remodeling lies at the core of most of these diseases. Sustained cardiac remodeling almost unavoidably ends in progressive muscle dysfunction, heart failure, and ultimately death. Therefore, in order to attenuate cardiac remodeling and reduce mortality, different therapies have been used, but it is important to identify adjuvant factors that can help to modulate this process. One of these factors is the inclusion of affordable foods in the diet with potential cardioprotective properties. Orange juice intake has been associated with several beneficial metabolic changes, which may influence cardiac remodeling induced by cardiovascular diseases. Current opinion highlights how the metabolites and metabolic pathways modulated by orange juice consumption could potentially attenuate cardiac remodeling. It was observed that orange juice intake significantly modulates phospholipids, energy metabolism, endocannabinoid signaling, amino acids, and gut microbiota diversity, improving insulin resistance, dyslipidemia, and metabolic syndrome. Specifically, modulation of phosphatidylethanolamine (PE) metabolism and activation of PPARα and PPARγ receptors, associated with improved energy metabolism, mitochondrial function, and oxidative stress, showed protective effects on the heart. Furthermore, orange juice intake positively impacted gut microbiota diversity and led to an increase in beneficial bacterial populations, correlated with improved metabolic syndrome. These findings suggest that orange juice may act as a metabolic modulator, with potential therapeutic implications for cardiac remodeling associated with cardiovascular diseases.

Inhalational anesthetic sevoflurane is commonly used in pediatric anesthesia. Multiple exposures to sevoflurane in early postnatal life have been associated with long-term abnormalities in myelin development and cognitive and memory impairments, although the underlying mechanisms remain incompletely elucidated. Disruption of gut microbiota is recognized as an important contributor to neurological diseases. Here, we explore the potential mechanisms underlying the abnormal myelin development induced by multiple sevoflurane exposures in neonatal rats by analyzing gut homeostasis.

Six-day-old (P6) C57BL/6 mice were exposed to 3% sevoflurane for 2 hours per day for three consecutive days. Mice exposed to a mixture of 60% nitrogen and oxygen under the same conditions and duration served as controls. Behavioral tests were conducted between P32 and P42. At P9 (24 hours after the last sevoflurane exposure) and P42 (after the completion of behavioral tests), intestinal and brain examinations were performed to investigate the effects of sevoflurane exposure during the lactation and adolescent periods on gut homeostasis and myelin development in mice. Subsequently, the ameliorative effects of butyrate supplementation on sevoflurane-induced abnormalities in myelin development and cognitive and memory impairments were observed.

After repeated exposure to sevoflurane, neonatal mice developed persistent gut microbiota imbalance accompanied by a decrease in short-chain fatty acids. Short-term intestinal inflammation emerged, with damage to the mucus layer and barrier function. In the hippocampus and prefrontal cortex, the expression of genes and transcription factors related to oligodendrocyte differentiation and myelin development was significantly affected, and these changes persisted even after the exposure ended. There was a reduction in proteins associated with oligodendrocytes and myelin formation, which had a certain impact on memory and cognitive behavior. This study also explored the potential connections between microbiota, metabolism, the gut, the brain, and behavior. Timely supplementation with butyrate could effectively reverse these changes, indicating that gut homeostasis is crucial for brain neurodevelopment.

Multiple exposures to sevoflurane in neonatal mice disrupt gut homeostasis and affect oligodendrocyte differentiation and myelin development in the hippocampus and prefrontal cortex, inducing cognitive and memory impairments. Supplementation with butyrate can alleviate these changes.

The gut microbiota is the collective term for the microorganisms that reside in the human gut. In recent years, advances in sequencing technology and bioinformatics gradually revealed the role of gut microbiota in human health. Dramatic changes in the gut microbiota occur during pregnancy due to hormonal and dietary changes, and these changes have been associated with certain gestational diseases such as preeclampsia (PE) and gestational diabetes mellitus (GDM). Modulation of gut microbiota has also been proposed as a potential treatment for these gestational diseases. The present article aims to review current reports on the association between gut microbiota and gestational diseases, explore possible mechanisms, and discuss the potential of probiotics in gestational diseases. Uncovering the link between gut microbiota and gestational diseases could lead to a new therapeutic approach.

Recent studies have highlighted the prebiotic potential of natural plant polysaccharides, demonstrating their role in promoting beneficial gut microbiota and improving health. However, research on the digestive properties and prebiotic activities of Imperatae Rhizoma Polysaccharides (IRPs) remains limited. This study investigated fresh Imperatae Rhizoma as the research object. After processing, dry Imperatae Rhizoma and carbonized Imperatae Rhizoma were prepared. Three polysaccharides from the fresh, dry, and carbonized Imperatae Rhizoma were extracted with traditional hot water. And another polysaccharide was obtained by cold water extraction from fresh Imperatae Rhizoma. Total four IRPs were extracted and named: IRPs-F, IRPs-D, IRPs-C, and IRPs-J. This study evaluated the prebiotic activity of four polysaccharides derived from the roots of thatch, demonstrating their resistance to digestion, their ability to promote probiotic growth, and their enhancement of short-chain fatty acid (SCFA) production. The final results show that four IRPs exhibit strong resistance to digestion and IRPs-F ability to promote the growth of beneficial probiotics, making it a promising candidate for functional foods aimed at improving intestinal health, immune regulation, and metabolic benefits. This research is highly relevant to food microbiology and holds significant potential for application in the functional food and gut health sectors.

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

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

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

As a traditional drug-food homologous plant, Dendrobium officinale is widely recognized for its nutritional and medicinal value. Specifically, D. officinale polysaccharide (DOP) has garnered attention as a potential prebiotic for its protective effects on gut microbiota and the nervous system. However, the underlying mechanism by which DOP improves cognitive dysfunction in Alzheimer's disease (AD) remains unclear. This study intends to elucidate the beneficial effects of DOP on AD mice from the perspectives of metabolomics and the intestinal microbiome. The results showed that DOP significantly ameliorated cognitive dysfunction, attenuated hippocampal neuronal damage and Aβ plaque deposition, and restored intestinal barrier integrity in AD mice. The antibiotic-cocktail-induced germ-free mouse model confirmed that the neuroprotective effect of DOP was dependent on gut microbiota. Further investigations demonstrated that DOP influenced the composition of gut microbiota and restored its diversity. Additionally, DOP reshaped metabolic profile disorders in AD mice and increased the short-chain fatty acids (SCFAs) content. Correlation analysis further highlighted that specific gut microbiota was associated with the metabolism of AD mice. In conclusion, this study sheds light on the positive impact of DOP in reshaping the gut microbiota and enhancing cognitive function, offering important perspectives for the possible advancement and utilization of DOP.

Studies on gut microbiome changes in neonatal Korean indigenous calves with diarrhea are rare. In this study, 14 normal calves and 11 calves with diarrhea were selected from Korean indigenous calves up to 30 days of age and classified into three groups at 10-day intervals (1-10, 11-20, and 21-30 days). Feces from 25 calves were collected, and the diversity, similarity, structure, and correlation of the gut microbiome were analyzed. Firmicutes, Bacteroidetes, and Proteobacteria were predominant in the taxonomic composition of the gut microbiome of the calves regardless of the presence of diarrhea. However, Proteobacteria increased and Bacteroidetes and Actinobacteria decreased in calves with diarrhea. In addition, calves with diarrhea showed a significant decrease in the diversity of the gut microbiome, especially for anaerobic microorganisms Faecalibacterium prausnitzii, Gemmiger formicilis, and Collinsella aerofaciens. The microbial communities in calves with diarrhea and normal calves were distinct. By analyzing the microorganisms that showed correlation with diarrhea and age using linear discriminant analysis effect size, at the genus level, Prevotella and Lachnospiraceae_uc were significantly related in the normal (11-20 days) group whereas Enterobacterales, Gammaproteobacteria, Enterobacteriaceae, Escherichia, and Proteobacteria were significantly associated with diarrhea in the 11-20 days group. Futhermore, the normal (21-30 days) group showed significant correlation with Blautia, Provotellaceae, Muribaculaceae, Christensenellaceae, and Catenella, whereas the diarrhea (21-30 days) group showed significant correlation with Dorea. The microorganisms associated with diarrhea in calves were mainly known as harmful microorganisms, we confirmed that there is a relationship between the increase in harmful bacteria and diarrhea. These results show that diarrhea significantly affects the gut microbiome of Korean indigenous calves. The changes in the gut microbiome of Korean indigenous calves observed in this study could be helpful in predicting and managing diarrhea calves, and furthermore, in establishing preventive measures for calf diarrhea through management of gut microbiome.

The objective of this research was to investigate the relationship between remnant cholesterol (RC) levels and suicide attempts (SA) made by Chinese patients with untreated first-episode major depressive disorder (UFE MDD).

This study included 1718 patients with UFE MDD. Demographic, clinical characteristics, and blood lipid parameters were collected. The 17-item Hamilton Depression Rating Scale (HAMD), the 14-item Hamilton Anxiety Rating Scale (HAMA), and the positive subscale of the Positive and Negative Syndrome Scale (PANSS) were used to assess their depression, anxiety, and psychotic symptoms, respectively. Multivariable binary logistic regression analysis was used to estimate the association between RC and the risk of SA. A two-piecewise linear regression model was used to investigate the threshold effects if non-linear associations existed.

Univariate logistic regression analysis showed a significant positive correlation between RC and SA, but after controlling for confounding factors, the association between them was not statistically significant. After dividing the RC into quartiles, only the RC in the Q4 group was significantly positively correlated with suicide attempts (OR = 1.73, 95% CI: 1.13-2.65, P = 0.012, vs. Q1) in a fully adjusted model. Curve fitting analysis also showed a nonlinear relationship between RC and suicide attempts with an inflection point at 1.99 mmol/L in RC. On the left of the inflection point, a significant positive correlation was observed between RC and SA (OR: 1.36, 95% CI: 1.09-1.69, p=0.006). However, on the right of the inflection point, no significant correlation was found (OR: 0.79, 95% CI: 0.55-1.14, p=0.214).

This study demonstrates a non-linear association between RC levels and SA in patients with untreated first-episode major depressive disorder. When RC was less than 1.99 mmol/L, they showed a significant positive correlation.

Stroke represents a predominant cause of mortality and disability on a global scale, impacting millions annually and exerting a considerable strain on healthcare systems. The incidence of stroke exhibits regional variability, with ischemic stroke accounting for the majority of occurrences. Post-stroke complications, such as cognitive impairment, motor dysfunction, and recurrent stroke, profoundly affect patients' quality of life. Recent advancements have elucidated the microbiota-gut-brain axis (MGBA), underscoring the complex interplay between gut health and brain function. Dysbiosis, characterized by an imbalance in gut microbiota, is significantly linked to an elevated risk of stroke and unfavorable outcomes. The MGBA plays a crucial role in modulating immune function, neurotransmitter levels, and metabolic byproducts, which may intensify neuroinflammation and impair cerebral health. This review elucidates the role of MGBA in stroke pathophysiology and explores potential gut-targeted therapeutic strategies to reduce stroke risk and promote recovery, including probiotics, prebiotics, pharmacological interventions, and dietary modifications. However, the current prevention and treatment strategies based on intestinal flora still face many problems, such as the large difference of individual intestinal flora, the stability of efficacy, and the long-term safety need to be considered. Further research needs to be strengthened to promote its better application in clinical practice.

Exercise is a widely recognized non-pharmacological treatment for Parkinson's Disease (PD). The bidirectional regulation between the brain and peripheral organs has emerged as a promising area of research, with the mechanisms by which exercise impacts PD closely linked to the interplay between peripheral signals and the central nervous system.

This review aims to summarize the mechanisms by which exercise influences peripheral-central crosstalk to improve PD, discuss the molecular processes mediating these interactions, elucidate the pathways through which exercise may modulate PD pathophysiology, and identify directions for future research.

This review examines how exercise-induced cytokine release promotes neuroprotection in PD. It discusses how exercise can stimulate cytokine secretion through various pathways, including the gut-brain, muscle-brain, liver-brain, adipose-brain, and bone-brain axes, thereby alleviating PD symptoms. Additionally, the potential contributions of the heart-brain, lung-brain, and spleen-brain axes, as well as multi-axis crosstalk-such as the brain-gut-muscle and brain-gut-bone axes-are explored in the context of exercise therapy. The study highlights the need for further research into peripheral-central crosstalk and outlines future directions to address challenges in clinical PD therapy.

Hyperlipidemia is regarded as one of the crucial factors leading to atherosclerosis and other cardiovascular diseases. Gut microbiota plays an important role in regulating host lipid metabolism. Nevertheless, the exact mechanisms behind this remain unclear.

In the present study, a hyperlipidemic zebrafish model was established using a high-cholesterol diet (HCD) to evaluate the anti-hyperlipidemic effects of Lactobacillus fermentum E15 (L. fermentum E15).

Results showed that L. fermentum E15 effectively reduced lipid accumulation in the blood vessels and liver of HCD-fed zebrafish larvae. Meanwhile, L. fermentum E15 improved abnormal lipid levels, and normalized liver enzyme activity. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis revealed that L. fermentum E15 downregulated the expression of sterol regulatory element-binding factor (SREBP-1), peroxisome proliferator-activated receptor-gamma (PPAR-γ), and fatty acid synthase (Fasn), while upregulated peroxisome proliferator-activated receptor-alpha (PPAR-α). Additionally, metabolomic analysis revealed that L. fermentum E15 produced a series of short-chain fatty acids (SCFAs), including acetic acid, propionic acid, butyric acid, and isovaleric acid. Notably, isovaleric acid contributed to the reduction of lipid droplet accumulation in the liver and blood vessels of HCD-fed zebrafish larvae. In contrast, blocking G-protein coupled receptor 43 (GPR43) with pertussis toxin (PTX) abolished the effects of L. fermentum E15 and isovaleric acid on reducing lipid accumulation in HCD-fed zebrafish larvae. RT-qPCR results further suggested that both L. fermentum E15 and isovaleric acid promoted the expression of GPR43 and leptin A, which was inhibited by PTX.

These findings suggested that L. fermentum E15 alleviates HCD-induced hyperlipidemia by activating GPR43 through SCFAs.

Accumulating evidence indicates that patients with liver diseases exhibit distinct microbiological profiles, which can be attributed to the bidirectional relationship of the gut-liver axis. Porto-sinusoidal vascular disease (PSVD) has recently been introduced to describe a group of vascular diseases of the liver, involving the portal venules and sinusoids. Although the pathophysiology of PSVD is not yet fully understood, several predisposing conditions, including immunodeficiency, inflammatory bowel disease, abdominal bacterial infections are associated with the increasing in intestinal permeability and microbial translocation, supporting the role of altered gut microbiota and gut-derived endotoxins in PSVD etiopathogenesis. Recent studies have proposed that the gut microbiome may play a crucial role in the pathophysiology of intrahepatic vascular lesions, potentially influencing the onset and progression of PSVD in this context. This review aims to summarize the current understanding of the gut microbiome's potential role in the pathogenesis of hepatic microvascular abnormalities and thrombosis, and to briefly describe their interactions with PSVD. The insights into gut microbiota and their potential influence on the onset and progression of PSVD may pave the way for new diagnostic, prognostic, and therapeutic strategies.

This study investigates the impact of maternal gestation diets with varying fiber contents on gene expression and chromatin accessibility in fetuses and piglets fed a low fiber diet post weaning. High-fiber maternal diets, enriched with sugar beet pulp or pea internal fiber, were compared to a low-fiber maternal diet to evaluate their effects on liver and muscle tissues. The findings demonstrate that maternal high-fiber diets significantly alter chromatin accessibility, predicted transcription factor activity and transcriptional landscape in both fetuses and piglets. A gene set enrichment analysis revealed over-expression of gene ontology terms related to metabolic processes and under-expression of those linked to immune responses in piglets from sows given the high-fiber diets during gestation. This suggests better metabolic health and immune tolerance of the fetus and offspring, in line with the documented epigenetic effects of short chain fatty acids on immune and metabolic pathways. A deconvolution analysis of the bulk RNA-seq data was performed using cell-type specific markers from a single cell transcriptome atlas of adult pigs. These results confirmed that the transcriptomic and chromatin accessibility data do not reflect different cell type compositions between maternal diet groups but rather phenotypic changes triggered by maternal nutrition in shaping the epigenetic and transcriptional environment of fetus and offspring. Our findings have implications for improving animal health and productivity as well as broader implications for human health, suggesting that optimizing maternal diet with high-fiber content could enhance metabolic health and immune function in the formative years after birth and potentially to adulthood.

The relationship between the gut microbiome and ocular health has garnered increasing attention within the scientific community. Recent research has focused on the gut-eye axis, examining whether imbalances within the gut microbiome can influence the development, progression and severity of ocular diseases, including dry eye disease, uveitis, and glaucoma. Dysbiosis within the gut microbiome is linked to immune dysregulation, chronic inflammation, and epithelial barrier dysfunction, all of which contribute to ocular pathology. This review synthesises current evidence on these associations, exploring how gut microbiome alterations drive disease mechanisms. Furthermore, it examines the therapeutic potential of microbiome-targeted interventions, including antibiotics, prebiotics, probiotics, and faecal microbiota transplantation, all of which aim to restore microbial balance and modulate immune responses. As the prevalence of these conditions continues to rise, a deeper understanding of the gut-eye axis may facilitate the development of novel, targeted therapies to address unmet needs in the management of ocular diseases.

Environmental factors can play fundamental role in health in childhood and adulthood during critical developmental periods like lactation. The maternal intake of probiotics like kefir during lactation could benefit newborns' intestinal health. This study aimed to evaluate the effects of maternal kefir intake during lactation on bacterial breast milk composition and the gut microbiota of offspring Wistar male rats at weaning. Lactating Wistar rats and their pups were divided into four groups based on litter size and maternal kefir intake. Sequencing of the 16S rRNA gene in breast milk revealed the predominance of the Proteobacteria, Firmicutes, and Actinobacteriota phyla. Offspring gut microbiota exhibited clustering tendencies in kefir groups with varying genus abundance. Additionally, maternal kefir intake led to increased levels of butyrate acid in offspring faeces (> +30%, p > 0.05). These findings show that the lactation period could be a window of opportunity to program intestinal health through microbiota modulation.

An alteration in the composition of the intestinal microbiota has been observed in patients with multiple sclerosis (pwMS) with respect to healthy controls (HC). Microorganism-derived metabolites such as short-chain fatty acids (SCFA) have been suggested to play a role in the disease. Thus, to analyze the association of SCFA with clinical and radiological parameters of the disease and with those related to the inflammatory response of the immune system.

Multicentric observational retrospective cross-sectional study. In addition 161 pwMS and 130 HC were included. The following plasma SCFA were analyzed using liquid chromatography coupled to mass spectrometry: acetate (AA), propionate (PA) and butyrate (BA). Blood cell subpopulations and cytokine expression were analyzed by flow cytometry.

Plasma PA and PA/AA ratio was lower in pwMS than in HC (P = 0.0001, and P = 0.00005, respectively). PA/AA and BA/AA ratios were lower in pwMS with higher disability (P = 0.001, and P = 0.001, respectively). T2 lesion load inversely correlated with PA/AA (r = -0.353; P = 0.002) and BA/AA (r = -0.322; P = 0.005) ratios. Plasma PA/AA and/or BA/AA ratios negatively correlated with the following pro-inflammatory cytokines producing cells: GM-CSF+CD4+T, GM-CSF+CD8+T, TNF-alpha+CD4+T, TNF-alpha+CD8+T, IFN-gamma+CD4+T, IFN-gamma+CD8+T, and TNF-alpha+B cells.

In MS, plasma PA/AA and BA/AA ratios are unbalanced, promoting an environment that could be boosting the mechanisms underlying the pathogenesis of the disease. Since we have found statistical significant associations with the EDSS and the number of T2 lesions, but not with the number of relapses or gadolinium enhancing lesions, PA/AA and BA/AA ratios could be more associated with those mechanisms of the disease related to the neurodegenerative processes than those related with the activity of the disease.

Perinatal depression and anxiety pose significant risks to maternal health and may lead to suicide. The gut microbiota may play a crucial role in perinatal depression and anxiety. However, the relationship between the alterations in gut microbiota and perinatal depression and anxiety remains unclear. This study aimed to investigate the dynamic changes of gut microbiota over various perinatal stages and their associations with perinatal depression and anxiety symptoms, especially suicide ideation.

A total of 177 pregnant and 19 postpartum women were recruited in this study, with 48 of them participating longitudinally. Maternal depression and anxiety symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS), 9-item Patient Health Questionnaire (PHQ-9), and 7-item Generalized Anxiety Disorder Scale (GAD-7). Fecal samples collected during the perinatal period were analyzed using 16S rRNA gene sequencing.

Significant changes in microbial diversity and multi-taxonomic levels were observed during pregnancy. The random forest regression model showed significant associations of some gut microbial features with depression and anxiety symptoms. Several genera were significantly associated with gestation age and perinatal depression and anxiety, such as Akkermansia, Bifidobacterium and Streptococcus. In addition, Erysipelotrichaceae_UCG-003 and Eubacterium_hallii_group were positively associated with suicidal ideation. The glycine biosynthesis pathway might act as a mediator between Eubacterium_hallii_group and suicidal ideation (ab = 3.27, p < 0.05).

The gut microbiota undergoes a programmed shift during pregnancy, which may play a critical role in perinatal depression and anxiety. Our findings underscore the impact of certain bacterial genera and metabolic pathways on perinatal mental health, which may help to develop new diagnostic tools and targeted interventions to reduce perinatal mental disorders and improve the outcomes for both mothers and infants.

Loureirin B (LB), an active component of Resina Draconis, exhibits hypoglycemic and hypolipidemic effects; however, its mode of action remains unclear. Here, ob/ob mice were utilized to investigate the effects of LB on the regulation of glucolipid metabolism disorders. Non-targeted metabolomics and 16S rDNA sequencing were performed to elucidate the potential mechanisms involved. Results indicated that LB treatment (45 mg/kg) significantly improved glucose intolerance and insulin resistance, reduced lipid levels, and alleviated hepatic steatosis. Non-targeted metabolomics analysis revealed that LB treatment regulated bile acid levels. Quantification of liver bile acids demonstrated that LB treatment significantly decreased the ratio of 12α-OH to non-12α-OH bile acids in the liver. 16S rDNA sequencing results showed that LB treatment increased the abundance of short-chain fatty acid-producing microbiota while decreasing the abundance of bile salt hydrolase (BSH) enzyme-producing microbiota. In conclusion, LB ameliorates glucolipid metabolism disorders by regulating liver bile acid levels and modulating the composition of the gut microbiota.

Multiple stressors are believed to deteriorate production performance and cause substantial economic losses in commercial poultry farming. Folic acid (FA) is an antioxidant compound that can improve oocyte function and regulate gut microbiota composition. The current study was conducted to investigate the role of FA in alleviating stress and improving production performance. Sixty Hyline Brown laying hens at 21 weeks of age were randomly divided into three groups, with 10 replicates in each group and each replicate containing two chickens. Each group received basic diet and saline injection (Con group), basic diet with dexamethasone (DXM) injection (DXM group), or basic diet supplemented with FA (13 mg/kg in the premix) with DXM injection (FA group). The feeding trial lasted five weeks. Birds in the DXM and FA groups receiving subcutaneous DXM injections at a dosage of 4.50 mg/kg per day during the first seven days of the trial. Results showed that the levels of corticosterone, triglyceride, total cholesterol, and malondialdehyde in serum were significantly increased in the DXM group (P < 0.05), while the concentrations of FA and 5-methyltetrahydrofolate were decreased in the DXM group (P < 0.05). Laying hens in the DXM group had lower laying rates and egg quality, including egg weight, eggshell thickness, eggshell strength, albumen height, and Haugh units (P < 0.05). Conversely, FA alleviated these negative impacts. Through transcriptome analysis, a total of 247 and 151 differentially expressed genes were identified among the three groups, and 32 overlapped genes were further identified. Moreover, 44 and 59 differential metabolites were influenced by DXM and FA, respectively. Kyoto Encyclopedia of Genes and Genomes enrichment from the transcriptome and metabolomics showed that the reduced production performance may be due to the disturbance of oocyte production, calcium metabolism, and oxidative stress. Analysis of 16S rRNA gene amplicon sequences revealed the differential microbial composition and potential functional changes among the different groups. LEfSe analysis showed that Mucispirillum and Nautella were the predominant bacteria in the DXM group, while Clostridium was the predominant bacteria in the FA group. Functional prediction demonstrated that stressors enhanced fatty acid biosynthesis, while betaine biosynthesis and retinol metabolism were elevated in the FA group. Dietary FA reversed the elevated levels of bile acids (BA), including cholic acid, taurodeoxycholic acid, and taurochenodeoxycholic acid (P < 0.05). The DXM group showed an overall decrease in short-chain fatty acids (SCFA), but FA restored the concentrations of acetic acid, propionic acid, and isobutyric acid (P < 0.05). In conclusion, this study reveals that dietary FA can alleviate the degradation of production performance caused by stress through improving circulating antioxidant capacity, maintaining intestinal microbiota homeostasis, and regulating SCFA and BA biosynthesis. Thus, highlighting the prominent role of gut microbe-host interactions in alleviating multi-stresses.

Nontyphoidal Salmonella strains (NTS) are among the most common foodborne enteropathogens and constitute a major cause of global morbidity and mortality, imposing a substantial burden on global health. The increasing antibiotic resistance of NTS bacteria has attracted a lot of research on understanding their modus operandi during infection. Growth in the gut lumen is a critical phase of the NTS infection. This might offer opportunities for intervention. However, the metabolic richness of the gut lumen environment and the inherent complexity and robustness of the metabolism of NTS bacteria call for modeling approaches to guide research efforts. In this study, we reconstructed a thermodynamically constrained and context-specific genome-scale metabolic model (GEM) for S. Typhimurium SL1344, a model strain well-studied in infection research. We combined sequence annotation, optimization methods and in vitro and in vivo experimental data. We used GEM to explore the nutritional requirements, the growth limiting metabolic genes, and the metabolic pathway usage of NTS bacteria in a rich environment simulating the murine gut. This work provides insight and hypotheses on the biochemical capabilities and requirements of SL1344 beyond the knowledge acquired through conventional sequence annotation and can inform future research aimed at better understanding NTS metabolism and identifying potential targets for infection prevention.

Kawasaki disease (KD) is an acute systemic immune vasculitis with predominant involvement of the medium and small arteries. It mostly affects pediatric patients, representing the most common form of pediatric vasculitis in children less than 5 years old. Numerous diseases, especially those related to the immune system, have established links with the intestinal flora. Recent studies have investigated the intestinal flora changes throughout the management of KD. There was gut microbiota dysbiosis in pediatric KD at the acute phase, particularly the downregulation of short-chain fat acids-producing microbiota and the over-proliferation of opportunistic pathogens. The relationship between the response to therapies in individuals with KD and specific microbiota remains uncertain. Targeted microbial supplements and dietary regulation may serve as potential measures to alleviate KD complications and thus improve prognosis. This review provides an overview of the current understanding of the interplay of the gut microbiota and KD. Furthermore, it discusses the possibility of altering the gut microbiota to reinstate a healthy condition.

In 2023, the World Obesity Atlas Federation concluded that more than 50% of the world's population would be overweight or obese within the next 12 years. At the heart of this epidemic lies the gut microbiota, a complex ecosystem that profoundly influences obesity-related metabolic health. Its multifaced role encompasses energy harvesting, inflammation, satiety signaling, gut barrier function, gut-brain communication, and adipose tissue homeostasis. Recognizing the complexities of the cross-talk between host physiology and gut microbiota is crucial for developing cutting-edge, microbiome-targeted therapies to address the global obesity crisis and its alarming health and economic repercussions. This narrative review analyzed the current state of knowledge, illuminating emerging research areas and their implications for leveraging gut microbial manipulations as therapeutic strategies to prevent and treat obesity and related disorders in humans. By elucidating the complex relationship between gut microflora and obesity, we aim to contribute to the growing body of knowledge underpinning this critical field, potentially paving the way for novel interventions to combat the worldwide obesity epidemic.

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

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

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

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