The brain imaging subtypes of schizophrenia have been widely investigated using data-driven approaches. However, the heterogeneity of SZ in multiple biological data is largely unknown.

A data-driven model was used to classify brain imaging, gut microbiota, and brain-gut fusion data obtained through a dot product fusion method, identifying significant subtypes and calculating their correlations with clinical symptoms and cognitive performance.

These subtypes remain relatively independent and demonstrate typical features and biomarkers, which are significantly associated with clinical symptoms and cognitive performance. Two brain subtypes with opposite structural and functional changes are identified: (1) a structural variant-dominant brain subtype with negative symptoms and cognitive deficits and (2) a functional alteration-dominant brain subtype with positive symptoms. The three gut subtypes include the following: (1) Collinsella-dominant; (2) Prevotella-dominant with positive symptoms; and (3) Streptococcus-dominant. Two brain-gut subtypes show different abnormalities in brain‒genus linkages: (1) strong connectivity of "brain function in the temporal and parietal lobes-Prevotella" with reduced attention scores and (2) strong connectivity of "brain structure and function in the frontal and parietal lobes-multiple genera" with positive symptoms. Notably, brain subtypes and brain-gut subtypes are most relevant to clinical symptoms, whereas gut subtypes reveal more cognitive biomarkers.

These findings show the potential to identify multiple biological subtypes with distinct biomarkers, thereby suggesting the possibility of personalized and precise treatment for SZ patients.

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

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.

The aim of this study was to evaluate the effects of lactic acid and glyceryl lactate on growth performance, antioxidant capacity, and intestinal health in piglets. This study included 240 castrated male piglets (initial body weight: 7.50 ± 0.54 kg) assigned to four groups: CON (basal diet), LA (basal diet + 0.5% lactic acid), GL (basal diet + 0.5% glyceryl lactate), and LG (basal diet + 0.5% lactic acid + 0.5% glyceryl lactate). Each group had six replicates of 10 piglets. The trial lasted 28 days. Compared with the control group, the GL and LG groups showed enhanced growth performance and reduced diarrhea rate in piglets. The LA and LG groups showed decreased intestinal chyme pH and increased digestive enzyme activities. Moreover, the GL and LG groups displayed elevated jejunal mRNA levels of the tight junction protein occludin and mucin MUC2, enhanced expression levels of Nrf2 signaling pathway genes, increased activities of the antioxidant enzymes GPX and CAT, and reduced MDA content. Acidifier supplementation also modulated cecal bacterial abundance and short-chain fatty acid (SCFA) content. Genera such as Faecalibaculum, Nocardiopsis, Collinsella, CAG269, Allobaculum, and Enterococcus were affected. In conclusion, glyceryl lactate and its combination with lactic acid improved piglet growth performance by enhancing intestinal barrier function, antioxidant capacity, microbial community structure, and SCFA production.

Gut microbiota plays a crucial role in resisting the invasion of pathogens, particularly multidrug-resistant (MDR) bacteria, which pose a significant threat to public health. While exercise offers numerous health benefits, its impact on host colonization resistance remains largely unclear. In this study, we demonstrate that moderate exercise significantly reduces gut colonization by methicillin-resistant Staphylococcus aureus (MRSA), a clinically important MDR pathogen. Moreover, we identify an understudied strain of the intestinal probiotic Dubosiella newyorkensis (L8) as a critical factor in mediating exercise-induced colonization resistance against MRSA. Mechanistically, L8 enhances the deprivation of fucose, a crucial carbon source essential for MRSA growth and pathogenicity. This process relies on the high binding affinity of pyruvate to the ILE257 site of the lactate dehydrogenase in L8. Overall, our work highlights the importance of moderate exercise in maintaining host colonization resistance and demonstrates L8 as a probiotic in protecting against MRSA colonization.

Traditional risk models for immunoglobulin A nephropathy (IgAN), which primarily rely on renal indicators, lack comprehensive assessment and therapeutic guidance, necessitating more refined and integrative approaches.

This study integrated network biomarkers with unsupervised learning clustering (k-means clustering based on network biomarkers [KMN]) to refine risk stratification in IgAN and explore its clinical value.

Involving a multicenter prospective cohort, we analyzed 1460 patients and validated the approach externally with 200 additional patients. Deeper metabolic and microbiomic insights were gained from 2 distinct cohorts: 63 patients underwent ultraperformance liquid chromatography-mass spectrometry, while another 45 underwent fecal 16S RNA sequencing. Our approach used hierarchical clustering and k-means methods, using 3 sets of indicators: demographic and renal indicators, renal and extrarenal indicators, and network biomarkers derived from all indicators.

Among 6 clustering methods tested, the KMN scheme was the most effective, accurately reflecting patient severity and prognosis with a prognostic accuracy area under the curve (AUC) of 0.77, achieved solely through cluster grouping without additional indicators. The KMN stratification significantly outperformed the existing International IgA Nephropathy Prediction Tool (AUC of 0.72) and renal function-renal histology grading schemes (AUC of 0.69). Clinically, this stratification facilitated personalized treatment, recommending angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for lower-risk groups and considering immunosuppressive therapy for higher-risk groups. Preliminary findings also indicated a correlation between IgAN progression and alterations in serum metabolites and gut microbiota, although further research is needed to establish causality.

The effectiveness and applicability of the KMN scheme indicate its substantial potential for clinical application in IgAN management.

The association between the human brain and gut microbiota, known as the "brain-gut-microbiota axis", is involved in the neuropathological mechanisms of schizophrenia (SZ); however, its association patterns and correlations with symptom severity and neurocognition are still largely unknown. In this study, 43 SZ patients and 55 normal controls (NCs) were included, and resting-state functional magnetic resonance imaging (rs-fMRI) and gut microbiota data were acquired for each participant. First, the brain features of brain images and functional brain networks were computed from rs-fMRI data; the gut features of gut microbiota abundance and the gut microbiota network were computed from gut microbiota data. Second, we propose a novel methodology to construct an individual brain-gut microbiota network (BGMN) for each participant by combining the brain and gut features via multiple strategies. Third, discriminative models between SZ patients and NCs were built using the connectivity matrices of the BGMN as input features. Moreover, the correlations between the most discriminative features and the scores of symptom severity and neurocognition were analyzed in SZ patients. The results showed that the best discriminative model between SZ patients and NCs was achieved using the connectivity matrices of the BGMN when all the brain and gut features were integrated, with an accuracy of 0.90 and an area under the curve value of 0.97. The most discriminative features were related primarily to the genera Faecalibacterium and Collinsella, in which the genus Faecalibacterium was linked to the visual system and subcortical cortices and the genus Collinsella was linked to the default network and subcortical cortices. Furthermore, parts of the most discriminative features were significantly correlated with the scores of neurocognition in the SZ patients. The methodology for constructing individual BGMNs proposed in this study can help us reveal the associations between the brain and gut microbiota and understand the neuropathology of SZ.

Exercise is a key component of lifestyle management in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but neither its therapeutic effect on the active stage of the disease, that is metabolic dysfunction-associated steatohepatitis (MASH) nor the mediating mechanisms have been characterized. Therefore, we performed multi-omic phenotyping of patients with MASLD-MASH on an exercise program.

Fifteen patients with MASLD conducted high-intensity interval training (HIIT) combined with home-based training for 12 weeks. MASLD was evaluated using histology, transient elastography, and multiparametric magnetic resonance imaging (MRI) before and after the intervention. Change in maximal oxygen consumption (VO2max) and MRI-determined liver fat were compared with a control group of patients with MASLD (n = 22). RNA sequencing was performed on liver, muscle, and fat biopsies of patients in the exercise group. Stool was analyzed by shotgun metagenomics and untargeted metabolomics was performed on plasma, urine, adipose, and stool.

HIIT increased VO2max by 10.1% and improved mitochondrial metabolism in skeletal muscle, indicating improved cardiorespiratory fitness and adherence. VO2max increased significantly in the exercise group compared with controls. Histologically, no reduction in steatosis, MASH, or liver fibrosis was observed; however, transient elastography tended to improve. MRI-determined liver fat did not change in the exercise group compared with controls. HIIT induced changes in mRNA expression of genes related to beiging of adipose tissue and fibrogenesis in liver. In addition, specific gut microbial taxa and metabolites changed.

HIIT increased cardiorespiratory fitness and induced beneficial gene expression changes in muscle, adipose tissue, and liver, but without translation into histological improvement of MASLD. Longer exercise intervention trials are warranted to validate or refute current recommendations for exercise as a cornerstone treatment for MASLD-MASH.

Despite exercise being considered as a key component of lifestyle management for steatotic liver disease, neither the clinical effects nor the mechanisms involved are completely understood. We show that a high-intensity interval training (HIIT) program in 15 patients with metabolic dysfunction-associated steatotic liver disease (MASLD) improved cardiorespiratory fitness, compared with 22 control patients with MASLD who did not participate in an exercise program, however, it did not improve MASLD. HIIT induced a positive effect on fat tissue and muscle metabolism which was accompanied with changes in certain gut bacteria and metabolites in blood and urine. These findings improve our understanding of the effects of exercise on the whole-body metabolism in relation to steatotic liver disease. As such, this study provides a basis for future exercise interventions in patients with MASLD, required to thoroughly test current guideline advice for exercise as a cornerstone treatment for MASLD of all stages.

Dutch Trial Register (registration number NL7932).

We aimed to investigate whether gut microbiota could predict the treatment response to pharmacological agents among metabolic dysfunction-associated steatotic liver disease (MASLD) patients without diabetes mellitus (DM), as data are lacking.

We prospectively followed up non-diabetic MASLD patients who used empagliflozin. Clinical, anthropometric, laboratory assessments and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) were performed from baseline to week 52 (EOT). Baseline stool samples were collected, and shotgun DNA metagenomic sequencing was performed to profile microbiome. The primary outcome was treatment response to empagliflozin at EOT, defined as MRI-PDFF decline ≥ 30% at EOT from baseline. Linear discriminant analysis [LDA] effect size was used to identify putative bacterial species. Multivariable logistic regression was used to derive adjusted odds ratio (aOR) of outcome with bacterial species by adjusting for clinical factors.

Twenty-two (48.9%) of 45 patients (median age: 56.9 years [IQR: 51.0-63.2]; male: 23 [51.1%]) achieved treatment response at EOT. There was difference in alpha diversity (Shannon index: p < 0.001; Simpson index: p = 0.001) and beta diversity (p = 0.048) in baseline microbiome between treatment response and non-response groups. Faecalibacterium prausnitzii (log10LDAscore = 4.27), Lachnospira pectinoschiza (log10LDAscore = 3.99), Anaerostipes hadrus (log10LDAscore = 3.98), Roseburia faecis (log10LDAscore = 3.97), Roseburia inulinivorans (log10LDAscore = 3.58) and Agathobaculum butyriciproducens (log10LDAscore = 2.77) were enriched in the treatment response group. L. pectinoschiza (aOR: 34.1; p = 0.015), A. hadrus (aOR:35.0; p = 0.032) and A. butyriciproducens (aOR:22.3; p = 0.023) independently predicted treatment response but not clinical factors. These three species collectively predicted treatment response with AUROC of 0.89 (95% CI: 0.80-0.99).

Certain gut bacterial species, particularly the combination of A. hadrus, L. pectinoschiza and A. butyriciproducens, may predict treatment response to empagliflozin in MAFLD patients without DM.

Non-alcoholic fatty liver disease (NAFLD) without special drugs shows symptoms of liver fat accumulation and steatosis in patients without alcohol intake. Ultrasound evaluation is a critical method in the early diagnosis of NAFLD stages as well as image processing and should be encouraged. Olive oil is an important component of the Mediterranean diet and has a beneficial role in the prevention of NAFLD progression. Physical activity and exercise can have anti-oxidant and anti-inflammatory effects to reduce liver fat and body weight via regulation of mitochondrial capacity in the development of NAFLD. Both the Mediterranean diet and physical exercise should be combined to achieve the ideal fat content reduction and weight loss in patients with NAFLD.

The purpose of this article is to present selected food additives as disruptors of normal intestinal homeostasis with a potential impact on the development of metabolic dysfunction-associated steatotic liver disease (MASLD). A comprehensive literature search was conducted in three major electronic databases: PubMed, ScienceDirect, and Google Scholar. MASLD is a prevalent liver condition that is closely related to the global rise in obesity. Its pathogenesis is multifactorial, with genetic, environmental, and metabolic factors playing a key role. The "multiple-hit" hypothesis suggests that a Western-style diet, rich in ultra-processed foods, saturated fats, and food additives, combined with low physical activity, contributes to obesity, which promotes lipid accumulation in the liver. Recent studies underscore the role of impaired intestinal homeostasis in the development of MASLD. Food additives, including preservatives, emulsifiers, and sweeteners, affect gut health and liver function. Selected preservatives inhibit pathogenic microorganisms but disrupt the intestinal microbiota, leading to changes in intestinal permeability and liver dysfunction. Some emulsifiers and thickeners can cause inflammation and alter the gut microbiome, contributing to liver steatosis. Furthermore, the use of sweeteners such as sucralose and aspartame has been linked to changes in liver metabolism and intestinal microbial composition, which in turn promotes metabolic disorders.

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) with a global prevalence of 30% is multifactorial and the involvement of gut bacteria has been recently proposed. However, finding robust bacterial signatures of NAFLD has been a great challenge, mainly due to its co-occurrence with other metabolic diseases.

Here, we collected public metagenomic data and integrated the taxonomy profiles with in silico generated community metabolic outputs, and detailed clinical data, of 1206 Chinese subjects w/wo metabolic diseases, including NAFLD (obese and lean), obesity, T2D, hypertension, and atherosclerosis. We identified highly specific microbiome signatures through building accurate machine learning models (accuracy = 0.845-0.917) for NAFLD with high portability (generalizable) and low prediction rate (specific) when applied to other metabolic diseases, as well as through a community approach involving differential co-abundance ecological networks. Moreover, using these signatures coupled with further mediation analysis and metabolic dependency modeling, we propose synergistic defined microbial consortia associated with NAFLD phenotype in overweight and lean individuals, respectively.

Our study reveals robust and highly specific NAFLD signatures and offers a more realistic microbiome-therapeutics approach over individual species for this complex disease. Video Abstract.

Hepatocellular carcinoma (HCC) is a heterogeneous tumor associated with several risk factors, with non-alcoholic fatty liver disease (NAFLD) emerging as an important cause of liver tumorigenesis. Due to the obesity epidemics, the occurrence of NAFLD has significantly increased with nearly 30% prevalence worldwide. HCC often arises in the background of chronic liver disease (CLD), such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Gut microbiome (GM) alterations have been linked to NAFLD progression and HCC development, with several investigations reporting a crucial role for the gut-liver axis and microbial metabolites in promoting CLD. Moreover, the GM affects liver homeostasis, energy status, and the immune microenvironment, influencing the response to immunotherapy with interesting therapeutic implications. In this review, we summarize the main changes in the GM and derived metabolites (e.g., short-chain fatty acids and bile acids) occurring in HCC patients and influencing NAFLD progression, emphasizing their potential as early diagnostic biomarkers and prognostic tools. We discuss the weight loss effects of diet-based interventions and healthy lifestyles for the treatment of NAFLD patients, highlighting their impact on the restoration of the intestinal barrier and GM structure. We also describe encouraging preclinical findings on the modulation of GM to improve liver functions in CLD, boost the antitumor immune response (e.g., probiotic supplementations or anti-hypercholesterolemic drug treatment), and ultimately delay NAFLD progression to HCC. The development of safe and effective strategies that target the gut-liver axis holds promise for liver cancer prevention and treatment, especially if personalized options will be considered.

Non-alcoholic fatty liver disease (NAFLD) is a multisystem metabolic disorder, marked by abnormal lipid accumulation and intricate inter-organ interactions, which contribute to systemic metabolic imbalances. NAFLD may progress through several stages, including simple steatosis (NAFL), non-alcoholic steatohepatitis (NASH), cirrhosis, and potentially liver cancer. This disease is closely associated with metabolic disorders driven by overnutrition, with key pathological processes including lipid dysregulation, impaired lipid autophagy, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and local inflammation. While hepatic lipid metabolism in NAFLD is well-documented, further research into inter-organ communication mechanisms is crucial for a deeper understanding of NAFLD progression. This review delves into intrahepatic networks and tissue-specific signaling mediators involved in NAFLD pathogenesis, emphasizing their impact on distal organs.

Rationale: Physical exercise is essential for skeletal integrity and bone health. The gut microbiome, as a pivotal modulator of overall physiologic states, is closely associated with skeletal homeostasis and bone metabolism. However, the potential role of intestinal microbiota in the exercise-mediated bone gain remains unclear. Methods: We conducted microbiota depletion and fecal microbiota transplantation (FMT) in ovariectomy (OVX) mice and aged mice to investigate whether the transfer of gut ecological traits could confer the exercise-induced bone protective effects. The study analyzed the gut microbiota and metabolic profiles via 16S rRNA gene sequencing and LC-MS untargeted metabolomics to identify key microbial communities and metabolites responsible for bone protection. Transcriptome sequencing and RNA interference were employed to explore the molecular mechanisms. Results: We found that gut microbiota depletion hindered the osteogenic benefits of exercise, and FMT from exercised osteoporotic mice effectively mitigated osteopenia. Comprehensive profiling of the microbiome and metabolome revealed that the exercise-matched FMT reshaped intestinal microecology and metabolic landscape. Notably, alterations in bile acid metabolism, specifically the enrichment of taurine and ursodeoxycholic acid, mediated the protective effects on bone mass. Mechanistically, FMT from exercised mice activated the apelin signaling pathway and restored the bone-fat balance in recipient MSCs. Conclusion: Our study underscored the important role of the microbiota-metabolic axis in the exercise-mediated bone gain, heralding a potential breakthrough in the treatment of osteoporosis.

Pneumatic resistance training (PRT) facilitates a longer time under tension that might lead to greater changes in body composition when compared to traditional resistance training (TRT), possibly enhancing serum metabolite concentrations indicative of healthy metabolic function. To assess the impact of PRT and TRT on muscular strength, body composition, and serum metabolome, 69 men (age: 31.8±7.2 years, height: 179.7±5.4 cm, weight: 81.1±9.9 kg) were randomized into two 10-week intervention groups (PRT:n=24 and TRT:n=24) and one control group (CON:n=21). Serum metabolite concentrations were assessed before and after the training intervention by high-throughput nuclear magnetic resonance. Fat mass and lean mass were obtained by bioimpedance analysis. The training intervention resulted in an increase in lean mass for both PRT (1.85±2.69%; p=0.003) and TRT (2.72±4.53%; p=0.004), while only PRT reduced statistically significantly in body fat percentage (PRT: -5.08±10.76%; p=0.019). Only in PRT and TRT significant increases in small high-density lipoproteins (S-HDL-L) and small HDL particles (S-HDL-P) were observed. When controlling for fat and lean mass, the effects on S-HDL-L/S-HDL-P diminished. Network analysis may suggest that PRT and TRT result in an increase in network connectivity and robustness. It appears that the observed improvements are associated with changes in body composition.

Extracellular vesicles (EVs) are involved in the progression of various diseases. Tumor cell-derived EVs (TEVs) are a particular concern, as they can induce fatty liver by promoting liver macrophages to secrete tumor necrosis factor (TNF), thus enhancing the toxicity of chemotherapy. Therefore, reducing pathogenic EV production is a potential strategy for treating EV-related diseases. However, there are currently no effective clinical reagents to obtain this purpose. In addition, EVs are also natural and ideal drug-delivery vehicles. Improving the delivery efficiency of EVs remains a challenge. Proton pump inhibitors (PPIs) have been demonstrated to promote cell uptake of EVs by inducing micropinocytosis. Here, we show that PPIs can accelerate TEV clearance, reduce TEV uptake by liver macrophages and decrease the mRNA expression of TNF in liver macrophages of tumor-bearing mice. Correspondingly, the fatty liver phenotypes are alleviated, and the tolerance to chemotherapy is improved in these mice. Furthermore, our findings indicate that PPIs facilitate the uptake of red blood cell-derived EVs (RBC-EVs) loaded with antisense oligonucleotides of Trim21 (Trim21-ASOs) by the liver macrophages of obesity. Consequently, the inhibition of macrophage inflammatory responses in obese mice mediated by RBC-EVs/Trim21-ASOs was further enhanced by PPIs, resulting in a more profound improvement in obesity and related metabolic disorders. In conclusion, our findings demonstrated that PPIs can effectively clear pathogenic EVs and enhance the delivery efficacy of EV vehicles, making them a highly promising clinical prospect.

The effects of physical activity and sedentary behavior on human health are well known, however, the molecular mechanisms are poorly understood. Growing evidence points to physical activity as an important modulator of the composition and function of microbial communities, while evidence of sedentary behavior is scarce. We aimed to synthesize and meta-analyze the current evidence about the effects of physical activity and sedentary behavior on microbiome across different body sites and in different populations.

A systematic search in PubMed, Web of Science, Scopus and Cochrane databases was conducted until September 2022. Random-effects meta-analyses including cross-sectional studies (active vs. inactive/athletes vs. non-athletes) or trials reporting the chronic effect of physical activity interventions on gut microbiome alpha-diversity in healthy individuals were performed.

Ninety-one studies were included in this systematic review. Our meta-analyses of 2632 participants indicated no consistent effect of physical activity on microbial alpha-diversity, although there seems to be a trend toward a higher microbial richness in athletes compared to non-athletes. Most of studies reported an increase in short-chain fatty acid-producing bacteria such as Akkermansia, Faecalibacterium, Veillonella or Roseburia in active individuals and after physical activity interventions.

Physical activity levels were positively associated with the relative abundance of short-chain fatty acid-producing bacteria. Athletes seem to have a richer microbiome compared to non-athletes. However, high heterogeneity between studies avoids obtaining conclusive information on the role of physical activity in microbial composition. Future multi-omics studies would enhance our understanding of the molecular effects of physical activity and sedentary behavior on the microbiome.

Background/Objectives: The human gut microbiome is a complex ecosystem of microorganisms that can influence our health and exercise habits. On the other hand, physical exercise can also impact our microbiome, affecting our health. Our narrative review examines the bidirectional relationship between physical activity and the gut microbiome, as well as the potential for targeted probiotic regimens to enhance sports performance. Methods: We conducted a comprehensive literature review to select articles published up till January 2024 on the topics of physical exercise, sports, probiotics, and gut microbiota from major scientific databases, incorporating over 100 studies. Results: We found that the impact of physical activity on the gut microbiome varies with the type and intensity of exercise. Moderate exercise promotes a healthy immune system, while high-intensity exercise for a long duration can cause a leaky gut and consequent systemic inflammation, which may disrupt the microbial balance. Combining aerobic and resistance training significantly affects bacterial diversity, linked to a lower prevalence of chronic metabolic disorders. Furthermore, exercise enhances gut microbiome diversity, increases SCFA production, improves nutrient utilization, and modulates neural and hormonal pathways, improving gut barrier integrity. Our findings also showed probiotic supplementation is associated with decreased inflammation, enhanced sports performance, and fewer gastrointestinal disturbances, suggesting that the relationship between the gut microbiome and physical activity is mutually influential. Conclusions: The bidirectional relationship between physical activity and the gut microbiome is exemplified by how exercise can promote beneficial bacteria while a healthy gut microbiome can potentially enhance exercise ability through various mechanisms. These findings underscore the importance of adding potential tailored exercise regimens and probiotic supplementation that consider individual microbiome profiles into exercise programs.

The prevalence, health and socioeconomic burden of metabolic dysfunction-associated fatty liver disease (MAFLD) is growing, increasing the need for novel evidence-based lifestyle approaches. Lifestyle is the cornerstone for MAFLD management and co-existing cardiometabolic dysfunction. The aim of this review was to evaluate the evidence for lifestyle management of MAFLD, with a specific lens on 24-hour integrated behaviour and provide practical recommendations for implementation of the evidence.

Weight loss ≥ 7-10% is central to lifestyle management; however, liver and cardiometabolic benefits are attainable with improved diet quality and exercise even without weight loss. Lifestyle intervention for MAFLD should consider an integrated '24-h' approach that is cognisant of diet, physical activity/exercise, sedentary behavior, smoking, alcohol intake and sleep. Dietary management emphasises energy deficit and improved diet quality, especially the Mediterranean diet, although sociocultural adaptations to meet preferences should be considered. Increasing physical activity and reducing sedentary behavior can prevent MAFLD, with strongest evidence in MAFLD supporting regular structured moderate-vigorous aerobic exercise for 150-240 min/week. Resistance training in addition to aerobic exercise should be considered and prioritised for those who are losing body mass via diet and/or pharmacological approaches and those with sarcopenia, to minimise bone and lean mass loss. Limited evidence suggests that sleep is important for MAFLD prevention. Emerging novel approaches to diet and exercise may address some of the key barriers to behaviour change (e.g. lack of time, access to resources and social support).

Large-scale multidisciplinary trials in people with MAFLD with long-term follow-up, that can be scaled up into mainstream healthcare, are required. Future management guidelines should consider the heterogeneity of MAFLD and specialised models of care that coordinate the health workforce to manage the increased and growing MAFLD population.

This review examines the complexities of Type 2 Diabetes Mellitus (T2DM), focusing on the critical role of integrating omics technologies with traditional experimental methods. It underscores the advancements in understanding the genetic diversity of T2DM and emphasizes the evolution towards personalized treatment modalities. The paper analyzes a variety of omics approaches, including genomics, methylation, transcriptomics, proteomics, metabolomics, and intestinal microbiomics, delineating their substantial contributions to deciphering the multifaceted mechanisms underlying T2DM. Furthermore, the review highlights the indispensable role of non-omics experimental techniques in comprehending and managing T2DM, advocating for their integration in the development of tailored medicine and precision treatment strategies. By identifying existing research gaps and suggesting future research trajectories, the review underscores the necessity for a comprehensive, multidisciplinary approach. This approach synergistically combines clinical insights with cutting-edge biotechnologies, aiming to refine the management and therapeutic interventions of T2DM, and ultimately enhancing patient outcomes. This synthesis of knowledge and methodologies paves the way for innovative advancements in T2DM research, fostering a deeper understanding and more effective treatment of this complex condition.

Gut microbiota plays key functions in the human body, and its alteration is associated with several human disorders. Moreover, its manipulation is being investigated as a potential therapeutic strategy. In this narrative review we will dissect the involvement of the gut microbiota and of the gut-liver axis on metabolic dysfunction-associated steatotic liver disease (MASLD). Additionally, we will review the effects of lifestyle interventions commonly used for MASLD (i.e. Mediterranean diet and physical exercise) on gut microbiome, to understand if their beneficial effect can be microbially mediated. Finally, we will discuss the role and the available evidence of therapeutic microbiome modulators, including prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT), in the management of MASLD.

This study aims to identify the gut enterotypes that explain differential responses to intervention with whole grain rye by proposing an "enterotype - metabolic" model.

A 12-week randomized controlled trial is conducted in Chinese adults, with 79 subjects consuming whole grain products with fermented rye bran (FRB) and 77 consuming refined wheat products in this exploratory post-hoc analysis. Responders or non-responders are identified according to whether blood glucose decreased by more than 10% after rye intervention. Compared to non-responders, responders in FRB have higher baseline Bacteroides (p < 0.001), associated with reduced blood glucose (p < 0.001), increased Faecalibacterium (p = 0.020) and Erysipelotrichaceae_UCG.003 (p = 0.022), as well as deceased 7β-hydroxysteroid dehydrogenase (p = 0.033) after intervention. The differentiated gut microbiota and metabolites between responders and non-responders after intervention are enriched in aminoacyl-tRNA biosynthesis.

The work confirms the previously suggested importance of microbial enterotypes in differential responses to whole grain interventions and supports taking enterotypes into consideration for improved efficacy of whole grain intervention for preventing type 2 diabetes. Altered short-chain fatty acids and bile acid metabolism might be a potential mediator for the beneficial effects of whole grain rye on glucose metabolism.

Gut microbiota plays a crucial role in maintaining host homeostasis, impacting the progression and therapeutic outcomes of diseases, including inflammatory bowel disease, cancer, hepatic conditions, obesity, cardiovascular pathologies, and neurologic disorders, via immune, neural, and metabolic mechanisms. Hence, the gut microbiota is a promising target for disease therapy. The safety and precision of traditional microbiota regulation methods remain a challenge, which limits their widespread clinical application. This limitation has catalyzed a shift toward the development of multifunctional delivery systems that are predicated on microbiota modulation. Guided by bioinspired strategies, an extensive variety of naturally occurring materials and mechanisms have been emulated and harnessed for the construction of platforms aimed at the monitoring and modulation of gut microbiota. This review outlines the strategies and advantages of utilizing bioinspired principles in the design of gut microbiota intervention systems based on traditional regulation methods. Representative studies on the development of bioinspired therapeutic platforms are summarized, which are based on gut microbiota modulation to confer multiple pharmacological benefits for the synergistic management of diseases. The prospective avenues and inherent challenges associated with the adoption of bioinspired strategies in the refinement of gut microbiota modulation platforms are proposed to augment the efficacy of disease treatment.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease globally, characterized by the accumulation of lipids, oxidative stress, and mitochondrial dysfunction in the liver. Celastrus orbiculatus Thunb. (COT) and its active compound celastrol (CEL) have demonstrated antioxidant and anti-inflammatory properties. Our prior research has shown the beneficial effects of COT in mitigating NAFLD induced by a high-fat diet (HFD) in guinea pigs by reducing hepatic lipid levels and inhibiting oxidative stress. This study further assessed the effects of COT on NAFLD and explored its underlying mitochondria-related mechanisms.

COT extract or CEL was administered as an intervention in C57BL/6J mice fed a HFD or in HepG2 cells treated with sodium oleate. Oral glucose tolerance test, biochemical parameters including liver enzymes, blood lipid, and pro-inflammatory factors, and steatosis were evaluated. Meanwhile, mitochondrial ultrastructure and indicators related to oxidative stress were tested. Furthermore, regulators of mitochondrial function were measured using RT-qPCR and Western blot.

The findings demonstrated significant reductions in hepatic steatosis, oxidative stress, and inflammation associated with NAFLD in both experimental models following treatment with COT extract or CEL. Additionally, improvements were observed in mitochondrial structure, ATP content, and ATPase activity. This improvement can be attributed to the significant upregulation of mRNA and protein expression levels of key regulators including FGF21, AMPK, PGC-1α, PPARγ, and SIRT3.

These findings suggest that COT may enhance mitochondrial function by activating the FGF21/AMPK/PGC-1α signaling pathway to mitigate NAFLD, which indicated that COT has the potential to target mitochondria and serve as a novel therapeutic option for NAFLD.

Monascus red pigments (MRP) may have benefits against NAFLD with an unclear mechanism. This study aimed to explore the protective effect of MRP supplementation against NAFLD through regulation of gut microbiota and metabolites. The C57BL/6 mice animals were randomly allocated into the normal diet (NC), HFHS diet-induced NAFLD model, and MRP intervention group fed with HFHS diet. Serum lipid profiles and liver function parameters were measured. Liver and colon histopathology analysis was conducted to determine the injury in the liver and colon. 16S rRNA gene sequencing was employed to analyze gut microbial composition from fecal samples. Untargeted metabonomics was performed to analyze changes in metabolites in serum and fecal samples. MRP supplementation significantly improved the HFHS-induced alterations in body weight, lipid profiles, and liver function (p < .01). MRP supplementation decreased the abundance of Akkermansia, Candidatus saccharimonas, Dubosiella, and Oscillibacter, while increasing Lactobacillus, Lachnospiraceae NK4A136 group, and Rikenella in mice fed the HFHS diet. Furthermore, MRP supplementation improved the serum and fecal metabolic profiles induced by the HFHS diet, primarily involving the arachidonic acid metabolism, unsaturated fatty acid biosynthesis, and adipocyte lipolysis pathways. Liver function and lipid profiles were closely associated with the abundance of Lactobacillus, Streptococcus, Oscillibacter, Akkemansia, and Desulfovibrio (p < .01). These findings revealed that MRP supplementation may help restore gut microbiota composition and balance its metabolites, thereby improving NAFLD. This study presents a novel outlook on the potential benefits of MRP supplementation in ameliorating NAFLD and supports the application of MRP as a new functional food.

The effective treatment of non-alcoholic fatty liver disease (NAFLD) is an unmet medical need. Qushi Huayu (QSHY) is an empirical herbal formula with promising effects in NAFLD rodent models and a connection to gut microbiota regulation.

This study aimed to evaluate the effects of QSHY in patients with NAFLD through a multicenter, randomized, double-blind, double-dummy clinical trial.

A total of 246 eligible patients with NAFLD and liver dysfunction were evenly divided to receive either QSHY and Dangfei Liganning capsule (DFLG) simulant or QSHY simulant and DFLG (an approved proprietary Chinese medicine for NAFLD in China) for 24 weeks. The primary outcomes were changes in liver fat content, assessed using vibration-controlled transient elastography, and serum alanine aminotransferase (ALT) levels from baseline to Week 24.

Both QSHY and DFLG led to reductions in liver fat content and liver enzyme levels post-intervention (p < 0.05). Compared to DFLG, QSHY treatment improved ALT (β, -0.128 [95 % CI, -0.25, -0.005], p = 0.041), aspartate transaminase (β, -0.134 [95 % CI, -0.256 to -0.012], p = 0.032), and fibrosis-4 score (β, -0.129 [95 % CI, -0.254 to -0.003], p = 0.044) levels. QSHY markedly improved gut dysbiosis compared to DFLG, with changes in Escherichia-Shigella and Bacteroides abundance linked to its therapeutic effect on reducing ALT. Patients with a high ALT response after QSHY treatment showed superior reductions in peripheral levels of phenylalanine and tyrosine, along with an elevation in the related microbial metabolite p-Hydroxyphenylacetic acid.

Our results demonstrate favorable clinical potential for QSHY in the treatment of NAFLD.

Bronchiectasis is marked by bronchial dilatation, recurrent infections and significant morbidity, underpinned by a complex interplay between microbial dysbiosis and immune dysregulation. The identification of distinct endophenotypes have refined our understanding of its pathogenesis, including its heterogeneous disease mechanisms that influence treatment and prognosis responses. Next-generation sequencing (NGS) has revolutionised the way we view airway microbiology, allowing insights into the "unculturable". Understanding the bronchiectasis microbiome through targeted amplicon sequencing and/or shotgun metagenomics has provided key information on the interplay of the microbiome and host immunity, a central feature of disease progression. The rapid increase in translational and clinical studies in bronchiectasis now provides scope for the application of precision medicine and a better understanding of the efficacy of interventions aimed at restoring microbial balance and/or modulating immune responses. Holistic integration of these insights is driving an evolving paradigm shift in our understanding of bronchiectasis, which includes the critical role of the microbiome and its unique interplay with clinical, inflammatory, immunological and metabolic factors. Here, we review the current state of infection and the microbiome in bronchiectasis and provide views on the future directions in this field.

Liver diseases contribute to ~2 million deaths each year and account for 4% of all deaths globally. Despite various treatment options, the management of liver diseases remains challenging. Physical exercise is a promising nonpharmacological approach to maintain and restore homeostasis and effectively prevent and mitigate liver diseases. In this review, we delve into the mechanisms of physical exercise in preventing and treating liver diseases, highlighting its effects on improving insulin sensitivity, regulating lipid homeostasis, and modulating immune function. In addition, we evaluate the impact of physical exercise on various liver diseases, including liver ischemia/reperfusion injury, cardiogenic liver disease, metabolic dysfunction-associated steatotic liver disease, portal hypertension, cirrhosis, and liver cancer. In conclusion, the review underscores the effectiveness of physical exercise as a beneficial intervention in combating liver diseases.

The ongoing debate surrounding the use of immunosuppressive treatments for IgA nephropathy (IgAN) underscores the demand for personalized and effective strategies.

Analyzed data from 807 IgAN patients over 5+ years using three methods: Random Forest with molecular biomarkers, network biomarkers with graph engineering, and an auto-encoder model. All models were trained using identical demographic, clinical, and pathological data, employing an 80-20 split for training and testing purposes.

In the comprehensive assessment of IgAN prognosis, the Random Forest model, employing molecular biomarkers, demonstrated strong performance metrics (AUC = 0.83, sensitivity = 0.51, specificity = 0.96). However, traditional graph feature engineering on patient-specific networks outperformed these results with an AUC of 0.90, sensitivity of 0.64, and specificity of 0.94. The Auto-encoder model showed the best accuracy (AUC = 0.91, sensitivity = 0.46, specificity = 0.96). The findings highlighted the superior predictive capabilities of network biomarkers over molecular biomarkers for adverse renal outcome prediction in IgAN. Consequently, we integrated Auto-encoder-derived Network Biomarkers with Random Forest Models to enhance prognostic precision in diverse IgAN treatment scenarios. The prediction for the prognosis of patients receiving supportive care, glucocorticoid therapy, and immunosuppressant treatment yielded AUC values of 0.95, 0.96, and 1, respectively, indicating high specificity. Drawing from these insights, we pioneered the development of an innovative decision support model for IgAN treatment. This model demonstrated the ability to make medical decisions comparable to those by experienced nephrologists, enabling the customization of personalized disease management strategies.

Our system accurately predicted IgAN prognosis and evaluated various treatment efficacies, aiding physicians in devising optimal therapeutic strategies for patients.

This study aimed to assess the response patterns of circulating lipids to exercise and diet interventions in nonalcoholic fatty liver disease (NAFLD).

The 8.6-month four-arm randomized controlled study comprised 115 NAFLD patients with prediabetes who were assigned to aerobic exercise (AEx; n = 29), low-carbohydrate diet (Diet; n = 28), AEx plus low-carbohydrate diet (AED; n = 29), and nonintervention (NI, n = 29) groups. Hepatic fat content (HFC) was quantified by proton magnetic resonance spectroscopy. Serum lipidomic analytes were measured using liquid chromatography-mass spectrometry.

After intervention, the total level of phosphatidylcholine (PC) increased significantly in the AEx group ( P = 0.043), whereas phosphatidylethanolamine (PE) and triacylglycerol decreased significantly in the AED group ( P = 0.046 and P = 0.036, respectively), and phosphatidylserine decreased in the NI group ( P = 0.002). Changes of 21 lipid metabolites were significantly associated with changes of HFC, among which half belonged to PC. Most of the molecules related to insulin sensitivity belonged to sphingomyelin (40 of 79). Controlling for the change of visceral fat, the significant associations between lipid metabolites and HFC remained. In addition, baseline serum lipids could predict the response of HFC to exercise and/or diet interventions (PE15:0/18:0 for AED, area under the curve (AUC) = 0.97; PE22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0 for AEx, AUC = 0.90; and PC14:1(9Z)/19:1(9Z) for Diet, AUC = 0.92).

Changes of lipidome after exercise and/or diet interventions were associated with HFC reductions, which are independent of visceral fat reduction, particularly in metabolites belonging to PC. Importantly, baseline PE could predict the HFC response to exercise, and PC predicted the response to diet. These results indicate that a circulating metabolomics panel can be used to facilitate clinical implementation of lifestyle interventions for NAFLD management.

Unhealthy lifestyles represent a key element fueling Non-alcoholic fatty liver disease (NAFLD) onset and worsening. We aimed to evaluate the effects of forced acute lifestyle changes on NAFLD evolution.

187 NAFLD patients were followed two years pre- and two years during the lockdown social restrictions in three Italian medical centers. For each patient, biochemical, clinical, non-invasive liver fibrosis, nutritional, and body composition data were collected.

An increase in fats and carbohydrate intake associated with impaired weekly physical activity during the lockdown was demonstrated as well as an increase in body mass index and waist-hip-ratio (p < 0.0001 for all). Total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, glucose, insulin, homeostatic model assessment for insulin resistance, and transaminases worsened during the lockdown (glucose: p = 0.0007; p < 0.0001 for the others). Moreover, NAFLD fibrosis score, liver stiffness, and controlled attenuation parameter were also impaired during the same period (p < 0.0001 for all). The bioelectrical impedance analysis (BIA) evidenced an increase of fat mass (FM), and a reduction of free fat mass (FFM) and body cell mass (BCM) (p < 0.0001 for all). The lockdown overall hepatocellular carcinoma (HCC) and Milan-out HCC occurrence revealed Hazard Ratio (HR): 2.398, 95% Confidence Interval (CI):1.16-5, p = 0.02, and HR:5.931, CI:2-17.6, p = 0.008 respectively. A liver disease stage and comorbidities independent association between both the assessed outcomes and body composition analysis in terms of mean values and variation (T1-T2 Δ) was demonstrated.

The acute lifestyle changes impacted NAFLD evolution via body composition modifications negatively influencing the HCC occurrence.

The equilibrium between gut microbiota (GM) and the host plays a pivotal role in maintaining overall health, influencing various physiological and metabolic functions. Emerging research suggests that exercise modulates the abundance and functionality of gut bacteria, yet the comprehensive effects on GM diversity remain to be synthesized.

The study aims to quantitatively examine the effect of exercise on the diversity of gut microbiota of adults using a systemic review and meta-analysis approach.

PubMed, Ebsco, Embase, Web of Science, Cochrane Central Register of Controlled Trials, the China National Knowledge Infrastructure, and Wanfang Data were searched from their inception to September 2023. Exercise intervention studies with a control group that describe and compare the composition of GM in adults, using 16S rRNA gene sequencing, were included in this meta-analysis.

A total of 25 studies were included in this meta-analysis with a total of 1044 participants. Based on a fixed-effects model [Chi2 = 29.40, df = 20 (p = 0.08); I2 = 32%], the pooled analysis showed that compared with the control group, exercise intervention can significantly increase the alpha diversity of adult GM, using the Shannon index as an example [WMD = 0.05, 95% CI (0.00, 0.09); Z = 1.99 (p = 0.05)]. In addition, exercise interventions were found to significantly alter GM, notably decreasing Bacteroidetes and increasing Firmicutes, indicating a shift in the Firmicutes/Bacteroidetes ratio. The subgroup analysis indicates that females and older adults appear to exhibit more significant changes in the Shannon Index and observed OTUs.

Exercise may be a promising way to improve GM in adults. In particular, the Shannon index was significantly increased after exercise. Distinct responses in GM diversity to exercise interventions based on gender and age implicated that more research was needed.

Recently, photogranules composed of bacteria and microalgae for carbon-negative nitrogen removal receive extensive attention worldwide, yet which type of bacteria is helpful for rapid formation of photogranules and whether they depend on signaling communication remain elusive. Varied signaling communication was analyzed using metagenomic method among bacteria and microalgae in via of two types of experimentally verified signaling molecule from bacteria to microalgae, which include indole-3-acetic acid (IAA) and N-acyl homoserine lactones (AHLs) during the operation of photo-bioreactors. Signaling communication is helpful for the adaptability of bacteria to survive with algae. Compared with non-signaling bacteria, signaling bacteria more easily adapt to the varied conditions, evidenced by the increased abundance in the operated reactors. Signaling bacteria are easier to enter the phycosphere, and they dominate the interactions between bacteria and algae rather than non-signaling bacteria. The co-abundance groups (CAGs) with signaling bacteria possess higher abundance than that without signaling bacteria (22.27 % and 6.67 %). Importantly, signaling bacteria accessibly interact with microalgae, which possess higher degree centralities and 32.50 % of them are keystone nodes in the network, in contrast to only 18.66 % of non-signaling bacteria. Thauera carrying both IAA and AHLs synthase genes are highly enriched and positively correlated with nitrogen removal rate. Our work not only highlights the essential roles of signaling communication between microalgae and bacteria in the development of photogranules, but also enriches our understanding of microbial sociobiology.

Regular exercise has both immediate and long-lasting benefits on cardiometabolic health, and has been recommended as a cornerstone of treatment in the management of diabetes and cardiovascular conditions. Exerkines, which are defined as humoral factors responsive to acute or chronic exercise, have emerged as important players conferring some of the multiple cardiometabolic benefits of exercise. Over the past decades, hundreds of exerkines released from skeletal muscle, heart, liver, adipose tissue, brain, and gut have been identified, and several exerkines (such as FGF21, IL-6, and adiponectin) have been exploited therapeutically as exercise mimetics for the treatment of various metabolic and cardiovascular diseases. Recent advances in metagenomics have led to the identification of gut microbiota, a so-called "hidden" metabolic organ, as an additional class of exerkines determining the efficacy of exercise in diabetes prevention, cardiac protection, and exercise performance. Furthermore, multiomics-based studies have shown the feasibility of using baseline exerkine signatures to predict individual responses to exercise with respect to metabolic and cardiorespiratory health. This review aims to explore the molecular pathways whereby exerkine networks mediate the cardiometabolic adaptations to exercise by fine-tuning inter-organ crosstalk, and discuss the roadmaps for translating exerkine-based discovery into the therapeutic application and personalized medicine in the management of the cardiometabolic disease.