Next-generation live biotherapeutics are promising to aid the treatment of obesity and metabolic diseases. Here, we reported a novel anti-obesity probiotic candidate, Roseburia hominis, that was depleted in stool samples of obese subjects compared with lean controls, and its abundance was negatively correlated with body mass index and serum triglycerides. Supplementation of R. hominis prevented body weight gain and disorders of glucose and lipid metabolism, prevented fatty liver, inhibited white adipose tissue expansion and brown adipose tissue whitening in mice fed with high-fat diet, and boosted the abundance of lean-related species. The effects of R. hominis could be partially attributed to the production of nicotinamide riboside and upregulation of the Sirtuin1/mTOR signaling pathway. These results indicated that R. hominis is a promising candidate for the development of next-generation live biotherapeutics for the prevention of obesity and metabolic diseases.

It has been suggested that the dietary approaches to stop hypertension (DASH) diet as a plant-based dietary pattern can be useful in improvement of risk factors of metabolic syndrome (MetS). We designed a study to evaluate the effect of the DASH diet on insulin resistance and lipid accumulation product (LAP) in subjects with MetS. 60 subjects with MetS were assigned into two groups including the intervention group and the control group. The intervention group received DASH diet and the control group received a common healthy diet for 12 weeks. We measured fasting plasma glucose (FPG), triglyceride and glucose (TyG) index, metabolic score for insulin resistance (METS-IR) and LAP before and after intervention. We utilized SPSS software version 24 and an intention-to-treat method for data analysis. A total of 59 subjects completed the trial. After intervention a significant difference was observed between groups in FPG (P < 0.001), TyG index (P < 0.001) and LAP (P = 0.01). However, there was no significant difference between groups in values of METS-IR (P = 0.27). There was a significant reduction in the intervention group compared to the control group in FPG (-7.86 ± 10.08 vs. 0.97 ± 15.51; P = 0.01), TyG index (-0.20 ± 0.14 vs. 0.02 ± 0.11; P < 0.001), METS-IR (-2.50 ± 1.99 vs. -0.53 ± 2.21; P = 0.001) and LAP (-20.06 ± 12.02 vs. -5.87 ± 15.17; P < 0.001). Adherence to DASH diet can reduce some cardiovascular risk factors in subjects with MetS. Further clinical trials are required to reach a firm conclusion.

Fat composition of milk replacer (MR) for calves differs from that of bovine milk fat, resulting in lower levels of butyric (C4:0) and caproic acid (C6:0). These fatty acids play a critical role in the gastrointestinal and metabolic development of calves by supporting rumen epithelial growth, enhancing energy metabolism, and promoting overall gut health. The objective of this study was to evaluate the effects of inclusion of a spray-dried fat concentrate containing tributyrin (TB) and tricaproin (TC) in a high-fat MR on growth, feed intake, and metabolic profiles of ad libitum-fed calves. Forty-eight newborn Holstein calves were blocked based on arrival sequence. Within each block of 2 calves, calves were randomly assigned to a control MR (CON, n = 24) including vegetable fats from palm, coconut, and linseed fats, or to an experimental MR including the same fat blend, to which TB and TC (TRI, n = 24) was added to the same levels found in milk fat. Both MR contained 23.7% crude protein, 27.7% fat, and 35.6% lactose (DM basis) and were fed at 13.5% solids. Calves were group housed and fed ad libitum MR with automated feeders. Weaning was gradual and induced between wk 7-10, after which calves were only fed solid feeds. Starter feed, chopped straw, and water were offered ad libitum throughout the whole study period. Calves were weighed and blood was collected once weekly at 1300h. Calves fed TRI showed a ∼50% reduction in therapeutic intervention days compared with CON. In addition, calves fed TRI consumed significantly more MR and starter feed, resulting in a greater growth. Serum NEFA and plasma total cholesterol were lower, whereas the enzymatic activity of serum ALP was higher in calves fed TRI than in CON. In addition, calves fed TRI had lower serum ghrelin and higher insulin-like growth factor-I concentrations. Incorporating TB and TC is a suitable strategy to increase solid feed intake upon weaning, resulting in better growth performance in ad libitum systems, and to improve health of dairy rearing calves.

Obesity (OB) has become a serious health issue owing to its ever-increasing prevalence over the past few decades due to its contribution to severe metabolic and inflammatory disorders such as cardiovascular disease, type 2 diabetes, and cancer. The unbalanced energy metabolism in OB is associated with substantial epigenetic changes mediated by the gut microbiome (GM) structure and composition alterations. Remarkably, experimental evidence also indicates that OB-induced epigenetic modifications in adipocytes can lead to cellular "memory" alterations, predisposing individuals to weight regain after caloric restriction and subsequently inducing inflammatory pathways in the liver. Various environmental factors, especially diet, play key roles in the progression or prevention of OB and OB-related disorders by modulating the GM structure and composition and affecting epigenetic mechanisms. Here, we will first focus on the key role of epigenetic aberrations in the development of OB. Then, we discuss the association between abnormal alterations in the composition of the microbiome and OB and the interplays between the microbiome and the epigenome in the development of OB. Finally, we review promising strategies, including prebiotics, probiotics, a methyl-rich diet, polyphenols, and herbal foods for the prevention and/or treatment of OB via modulating the GM and their metabolites influencing the epigenome.

Dysbiosis, which refers to an imbalance in the composition of the gut microbiome, has been associated with a range of metabolic disorders, including type 2 diabetes, obesity, and metabolic syndrome. Although the exact mechanisms connecting gut dysbiosis to these conditions are not fully understood, various lines of evidence strongly suggest a substantial role for the interaction between the gut microbiome, mitochondria, and epigenetics. Current studies suggest that the gut microbiome has the potential to affect mitochondrial function and biogenesis through the production of metabolites. A well-balanced microbiota plays a pivotal role in supporting normal mitochondrial and cellular functions by providing metabolites that are essential for mitochondrial bioenergetics and signaling pathways. Conversely, in the context of illnesses, an unbalanced microbiota can impact mitochondrial function, leading to increased aerobic glycolysis, reduced oxidative phosphorylation and fatty acid oxidation, alterations in mitochondrial membrane permeability, and heightened resistance to cellular apoptosis. Mitochondrial activity can also influence the composition and function of the gut microbiota. Because of the intricate interplay between nuclear and mitochondrial communication, the nuclear epigenome can regulate mitochondrial function, and conversely, mitochondria can produce metabolic signals that initiate epigenetic changes within the nucleus. Given the epigenetic modifications triggered by metabolic signals from mitochondria in response to stress or damage, targeting an imbalanced microbiota through interventions could offer a promising strategy to alleviate the epigenetic alterations arising from disrupted mitochondrial signaling.

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

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

Black raspberry as a functional food is a potential modulator of human metabolic disease. However, the role of black raspberry polyphenols (HSM) in shaping metabolic dysregulation and perturbation in gut microbiota (GM) to promote lipid metabolism and liver regeneration is unclear. In this work, the effects of HSM in mitigating metabolic disturbances and hepatic damage induced by a high-fat diet (HFD) and antibiotics (Abs) in mice were measured. HSM significantly alleviated HFD-induced obesity, insulin resistance, lipid and glucose metabolic dysregulation, as well as hepatic damage by activating the PI3K/AKT pathway and pregnane X receptor (PXR)-farnesoid X receptor (FXR) axis with improved GM, which was evidenced by short-chain fatty acids, 16S, and nontarget metabolism analysis. Excellent results were also evident in mice treated with Abs. Besides, HSM markedly inhibited key digestive enzymes associated with metabolic syndrome and also significantly enhanced antioxidant capacity after metabolized by GM. The discoveries underscored the potential of dietary HSM to manage lipid metabolism and liver regeneration within GM homeostasis.

Alexander disease (AxD) is a rare leukodystrophy caused by heterozygous mutations in the GFAP gene. To date, several in vitro and in vivo models have been generated in an attempt to unravel the main mechanisms underlying this complex disease. However, none of these models is suitable for investigating the global dysregulation caused by AxD. To address this shortcoming, we have generated a stable transgenic zebrafish line (zAxD) carrying the human GFAP p.R239C mutation, which is associated with severe phenotypes of AxD type I patients. We then performed transcriptomics and proteomics analyses on the whole larvae of our zAxD model, confirming the involvement of several pathways such as the immune system response and inflammation, oxidative stress, extracellular matrix, lipoxidation and lipid metabolism, which were previously reported in more limited omic studies. Interestingly, new pathways emerged as well, including tyrosine and butanoate metabolic processes. Biochemical assays confirmed alterations in cell respiration and lipid metabolism as well as elevated oxidative stress. These findings confirm the reliability of the zAxD model to apply a whole-organism approach to investigate the molecular basis of the disease.

Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern that is closely linked to metabolic syndrome, yet no approved pharmacological treatment exists. The Mediterranean diet (MD) emerged as a first-line dietary intervention for NAFLD, offering metabolic and hepatoprotective benefits. Now conceptualized as a complex chemical matrix rich in bioactive compounds, the MD exerts antioxidant and anti-inflammatory effects, improving insulin sensitivity and lipid metabolism. Mitochondria play a central role in NAFLD pathophysiology, influencing energy metabolism, oxidative stress, and lipid homeostasis. Emerging evidence suggests that the MD's bioactive compounds enhance mitochondrial function by modulating oxidative phosphorylation, biogenesis, and mitophagy. However, most research has focused on individual compounds rather than the MD as a whole, leaving gaps in understanding its collective impact as a complex dietary pattern. This narrative review explores how the MD and its bioactive compounds influence mitochondrial health in NAFLD, highlighting key pathways such as mitochondrial substrate control, dynamics, and energy efficiency. A literature search was conducted to identify relevant studies on the MD, mitochondria, and NAFLD. While the search was promising, our understanding remains incomplete, particularly when current knowledge is limited by the lack of mechanistic and comprehensive studies on the MD's holistic impact. Future research integrating cutting-edge experimental approaches is needed to elucidate the intricate diet-mitochondria interactions. A deeper understanding of how the MD influences mitochondrial health in NAFLD is essential for developing precision-targeted nutritional strategies that can effectively prevent and manage the disease.

Short-chain fatty acids have been reported to have anti-inflammatory and antioxidant functions; whether isobutyrate, a short-chain fatty acid, is protective against liver injury in a dextran sodium sulfate (DSS)-induced colitis and its molecular mechanism is unknown. In this study, DSS was used to induce a liver injury from a colitis model in piglets, which was expected to prevent and alleviate DSS-induced liver injury by feeding sodium isobutyrate in advance.

The results showed that sodium isobutyrate could restore DSS-induced histopathological changes in the liver, inhibit the activation of the toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa-B signaling pathway, and then reduce the DSS-induced release of pro-inflammatory cytokines tumor necrosis factor-α, interleukin 1β, and interleukin 6, reducing inflammatory response. Moreover, we found that sodium isobutyrate could play an antioxidant and apoptosis-reducing role by maintaining reduced mitochondrial function.

In conclusion, sodium isobutyrate has a preventive and protective effect on liver injury in a DSS-induced colitis. There is a potential application prospect for it in treating ulcerative-colitis-induced liver injuries. © 2024 Society of Chemical Industry.

The harsh conditions of the Qinghai-Tibet Plateau pose significant physiological challenges to local fauna, often resulting in gastrointestinal disorders. However, Tibetan pigs have exhibited remarkable adaptability to the high-altitude stress of the Tibetan Plateau, a phenomenon that remains not fully understood in terms of their gastrointestinal microbiota. This study collected 57 gastrointestinal tract samples from Tibetan pigs (n = 6) and plain black pigs (n = 6) with comparable genetic backgrounds. Samples from the stomach, jejunum, cecum, colon, and rectum, underwent comprehensive metagenomic analysis to elucidate the gut microbiota-related adaptive mechanisms in Tibetan pigs to the extreme high-altitude environment. A predominance of Pseudomonadota was observed within gut microbiome of Tibetan pigs. Significant differences in the microbial composition were also identified across the tested gastrointestinal segments, with 18 genera and 141 species exhibiting differential abundance. Genera such as Bifidobacterium, Megasphaera, Fusobacterium, and Mitsuokella were significantly more abundant in Tibetan pigs than in their lowland counterparts, suggesting specialized adaptations. Network analysis found greater complexity and modularity in the microbiota of Tibetan pigs compared to black pigs, indicating enhanced ecological stability and adaptability. Functional analysis revealed that the Tibetan pig microbiota was particularly enriched with bacterial species involved in metabolic pathways for propionate and butyrate, key short-chain fatty acids that support energy provision under low-oxygen conditions. The enzymatic profiles of Tibetan pigs, characterized by elevated levels of 4-hydroxybutyrate dehydrogenase and glutaconyl-CoA decarboxylase, highlighted a robust fatty acid metabolism and enhanced tricarboxylic acid cycle activity. In contrast, the gut microbiome of plain black pigs showed a reliance on the succinate pathway, with a reduced butyrate metabolism and lower metabolic flexibility. Taken together, these results demonstrate the crucial role of the gastrointestinal microbiota in the adaptation of Tibetan pigs to high-altitude environments by optimizing carbohydrate metabolism and short-chain fatty acid production for efficient energy utilization. This study not only highlights the metabolic benefits conferred by the gut microbiota of Tibetan pigs in extreme environments, but also advances our understanding of the adaptive gastrointestinal mechanisms in plateau-dwelling animals. These insights lay the foundation for exploring metabolic interventions to support health and performance in high-altitude conditions.

Evidence is accumulating that short-chain fatty acids (SCFAs) produced by the gut microbiota play pivotal roles in host metabolism. They contribute to the metabolic regulation and energy homeostasis of the host not only by preserving intestinal health and serving as energy substrates but also by entering the systemic circulation as signaling molecules, affecting the gut-brain axis and neuroendocrine-immune network. This review critically summarizes the current knowledge regarding the effects of SCFAs in the fine-tuning of the pathogenesis of type 2 diabetes mellitus (T2DM) and insulin resistance, with an emphasis on the complex relationships among diet, microbiota-derived metabolites, T2DM inflammation, glucose metabolism, and the underlying mechanisms involved. We hold an optimistic view that elucidating how diet can influence gut bacterial composition and activity, SCFA production, and metabolic functions in the host will advance our understanding of the mutual interactions of the intestinal microbiota with other metabolically active organs, and may pave the way for harnessing these pathways to develop novel personalized therapeutics for glucometabolic disorders.

Metabolic syndrome (MetS) constitutes a spectrum of interconnected conditions comprising obesity, dyslipidemia, hypertension, and insulin resistance (IR). While a singular, all-encompassing treatment for MetS remains elusive, an integrative approach involving tailored lifestyle modifications and emerging functional food therapies holds promise in preventing its multifaceted manifestations. Our main objective was to scrutinize the efficacy of cranberry proanthocyanidins (PAC, 200 mg/kg/day for 12 weeks) in mitigating MetS pathophysiology in male mice subjected to standard Chow or high-fat/high-fructose (HFHF) diets while unravelling intricate mechanisms. The administration of PAC, in conjunction with an HFHF diet, significantly averted obesity, evidenced by reductions in body weight, adiposity across various fat depots, and adipocyte hypertrophy. Similarly, PAC prevented HFHF-induced hyperglycemia and hyperinsulinemia while also lessening IR. Furthermore, PAC proved effective in alleviating key risk factors associated with cardiovascular diseases by diminishing plasma saturated fatty acids, as well as levels of triglycerides, cholesterol, and non-HDL-C levels. The rise in adiponectin and drop in circulating levels of inflammatory markers showcased PAC's protective role against inflammation. To better clarify the mechanisms behind PAC actions, gut-liver axis parameters were examined, showing significant enhancements in gut microbiota composition, microbiota-derived metabolites, and marked reductions in intestinal and hepatic inflammation, liver steatosis, and key biomarkers associated with endoplasmic reticulum (ER) stress and lipid metabolism. This study enhances our understanding of the complex mechanisms underlying the development of MetS and provides valuable insights into how PAC may alleviate cardiometabolic dysfunction in HFHF mice.

β-Glucan is a fermentable polysaccharide with prebiotic properties that has been shown to improve metabolic indicators. This study evaluated the effects of spent brewer's yeast β-glucan (BGL) and Lactobacillus acidophilus LA-5 (106 CFU/g) (LA5) alone and in combination (LA5-BGL) on the composition of the fecal microbiome of adults with type 2 diabetes mellitus (T2DM) using the Human Gut Microbial Ecosystem Simulator (SHIME®). Short-chain fatty acids (SCFAs), ammonium ions, and cytokines (IL-6 and IL-10) were measured. BGL, LA5, and LA5-BGL increased (p < 0.05) the richness and diversity of microbial communities in the gut microbiome of individuals with T2DM. All treatments increased (p < 0.05) the abundance of Bacteroides, Alistipes, Lactobacillus, Subdoligranulum, and Acidaminococcus, along with increased (p < 0.05) production of SCFAs and anti-inflammatory cytokine (IL-10) compared to the control group. BGL treatments showed a greater increase in microbial diversity, SCFAs levels (butyric, propionic, and acetic acid), and the anti-inflammatory cytokine (IL-10). LA5 showed the highest decrease in ammonium ion levels. Results indicate that BGL may have a prebiotic and immunomodulatory effect on the fecal microbial community and metabolic indicators in adults with type 2 diabetes mellitus (T2DM). Findings underscore the role of BGL as a prebiotic food.

The rising global concern over antibiotic resistance has heightened scrutiny of antibiotic growth promoters (AGPs) in poultry farming, prompting a shift toward alternative feed additives to ensure sustainable and safe poultry production. This trend aligns with the increasing demand for free-range and naturally raised chicken meat in various regions, including Indonesia. In response, Indonesian breeders have turned to medium-sized male layer chickens (MLCs) as substitutes for traditional free-range chickens. This practice, coupled with the need to replace AGPs, highlights the critical importance of exploring innovative and natural solutions to enhance poultry growth and health.

This study investigated the effects of probiotics as an alternative to AGPs on the growth performance, carcass traits, and immune organs of male ISA Brown layer chickens.

The 180-day-old male ISA Brown layer chickens were used for the study. The intervention included six treatments. T1 basal feed, T2 2.5 g AGP/kg feed, T3 1 ml probiotic/kg feed, T4 3 ml probiotic/kg feed, T5 4 ml probiotic/kg feed, and T6 5 ml probiotic/kg feed. Probiotics used were Lactobacillus acidophilus, Bifidobacterium sp., and Lactobacillus plantarum at a concentration of 1.2 × 109 CFU/ml. The feeding trial lasted for 21 days for chickens aged 21-42 days, assessing growth performance [body weight, feed consumption, digestibility, and feed conversion ratio (FCR)], carcass traits, non-edible organs, and immune organs.

The findings demonstrate that probiotic supplementation significantly outperformed the AGP-treated group (T2) in enhancing growth performance, carcass weight, pectoral weight development, FCR, internal and immune organ weights, nutrient intake, and digestibility. While AGPs showed improvements over the control (T1), probiotic- supplemented groups, particularly T6, achieved superior results across all parameters, indicating that probiotics are not only a viable alternative to AGPs but also a more effective and sustainable approach for poultry production.

The probiotics used in the study at 4 and 5 ml/kg of feed significantly enhanced the performance, immune organ development, and carcass attributes of MLCs, demonstrating their effectiveness as a viable alternative to AGPs. These findings highlight the potential of probiotics to improve poultry production sustainability by reducing reliance on antibiotics, enhancing growth and health outcomes, and promoting animal welfare through natural and efficient dietary interventions.

This study investigated the effects of long-term NaHCO3 stress on serum immunity, antioxidant capacity, intestinal tight junction, intestinal microbiota, mitochondrial function and autophagy in crucian carp. A total of 240 fish (31.19 ± 1.03 g) were randomly allocated to two groups and treated with 0 mmol/L (CK) and 50 mmol/L NaHCO3 (CA) respectively, to simulate the carbonate alkaline water environment. All of the experimental fish were cultured for 8 weeks. The results showed that compared to the control group, NaHCO3 stress significantly decreased the levels of the serum immunity indices (AKP, ACP, C3, C4, IgM, LZM) and the antioxidant capacity indices (CAT, GSH-PX, SOD, T-AOC), while markedly increasing the content of MDA. Additionally, NaHCO3 influenced the mRNA expression of HSP90, Nrf2, Keap1, and HO-1. Compared to the control group, the levels of ZO-1, Claudin-2, Occludin-a, and Occludin-b mRNA significantly decreased in the NaHCO3 stress group. The levels of ATG5, ATG7, and Beclin1 mRNA and protein were significantly increased along with the levels of LC3b mRNA and the ratio of protein LC3 II /LC3 I. Compared to the control group, intestinal mitochondria in the NaHCO3 stress group were visibly swollen and largely broken, with reductions in ridges and a large proportion of the area dissolved in the matrix. The mitochondrial membrane potential and the activities of ATPase were significantly decreased, leading to mitochondria dysfunction. In addition, 3147 differentially expressed genes were identified from transcriptome sequencing, among which several genes related to mitochondria and autophagy were significantly enriched. Compared to the control group, the NaHCO3 stress decreased the ACE index and increased the abundance of Proteobacteria while decreased the abundance of Actinobacteria and Firmicutes. In conclusion, NaHCO3 induced oxidative damage, microbiota alterations, mitochondria dysfunction, and autophagy in the intestines of crucian carp. The results of this study have characterized the molecular mechanisms of intestinal injury in crucian carp caused by NaHCO3 stress, and thus provide empirical support for aquaculture in saline-alkali waters.

The gut microbiota influences aspects of metabolic disease, including tissue inflammation, adiposity, blood glucose, insulin, and endocrine control of metabolism. Prebiotics or probiotics are often sought to combat metabolic disease. However, prebiotics lack specificity and can have deleterious bacterial community effects. Probiotics require live bacteria to find a colonization niche sufficient to influence host immunity or metabolism. Postbiotics encompass bacterial-derived components and molecules, which are well-positioned to alter host immunometabolism without relying on colonization efficiency or causing widespread effects on the existing microbiota. Here, we summarize the potential for beneficial and detrimental effects of specific postbiotics related to metabolic disease and the underlying mechanisms of action. Bacterial cell wall components, such as lipopolysaccharides, muropeptides, lipoteichoic acids and flagellin, have context-dependent effects on host metabolism by engaging specific immune responses. Specific types of postbiotics within broad classes of compounds, such as lipopolysaccharides and muropeptides, can have opposing effects on endocrine control of host metabolism, where certain postbiotics are insulin sensitizers and others promote insulin resistance. Bacterial metabolites, such as short-chain fatty acids, bile acids, lactate, glycerol, succinate, ethanolamine, and ethanol, can be substrates for host metabolism. Postbiotics can fuel host metabolic pathways directly or influence endocrine control of metabolism through immunomodulation or mimicking host-derived hormones. The interaction of postbiotics in the host-microbe relationship should be considered during metabolic inflammation and metabolic disease.

It is critical to sustain the diversity of the microbiota to maintain host homeostasis and health. Growing evidence indicates that changes in gut microbial biodiversity may be associated with the development of several pathologies, including type 2 diabetes mellitus (T2DM). Metformin is still the first-line drug for treatment of T2DM unless there are contra-indications. The drug primarily inhibits hepatic gluconeogenesis and increases the sensitivity of target cells (hepatocytes, adipocytes and myocytes) to insulin; however, increasing evidence suggests that it may also influence the gut. As T2DM patients exhibit gut dysbiosis, the intestinal microbiome has gained interest as a key target for metabolic diseases. Interestingly, changes in the gut microbiome were also observed in T2DM patients treated with metformin compared to those who were not. Therefore, the aim of this review is to present the current state of knowledge regarding the association of the gut microbiome with the antihyperglycemic effect of metformin. Numerous studies indicate that the reduction in glucose concentration observed in T2DM patients treated with metformin is due in part to changes in the biodiversity of the gut microbiota. These changes contribute to improved intestinal barrier integrity, increased production of short-chain fatty acids (SCFAs), regulation of bile acid metabolism, and enhanced glucose absorption. Therefore, in addition to the well-recognized reduction of gluconeogenesis, metformin also appears to exert its glucose-lowering effect by influencing gut microbiome biodiversity. However, we are only beginning to understand how metformin acts on specific microorganisms in the intestine, and further research is needed to understand its role in regulating glucose metabolism, including the impact of this remarkable drug on specific microorganisms in the gut.

Butyrate, a short-chain fatty acid, is a crucial product of gut microbial fermentation with significant implications for various metabolic and physiological processes. Dietary sources of butyrate are limited, primarily derived from the fermentation of dietary fibers by butyrate-producing gut bacteria. Butyrate exerts its effects primarily as a histone deacetylase (HDAC) inhibitor and through signaling pathways involving G protein-coupled receptors (GPCRs). Its diverse benefits include promoting gut health, enhancing energy metabolism, and potentially alleviating complications associated with obesity. However, the exact role of butyrate in obesity is still under investigation, with a limited number of human trials necessitating further research to determine its efficacy and safety profile. Moreover, butyrate impact on the gut-brain axis and its modulation of microbiome effect on behavior highlight its broader importance in regulating host physiology. A thorough understanding of the metabolic pathways and mechanisms of butyrate is essential for developing targeted interventions for metabolic disorders. Continued research is crucial to fully realize its therapeutic potential and optimize its clinical applications in human health. In summary, this review illuminates the multifaceted role of butyrate as a potential mediator of obesity and related metabolic changes.

Type 2 diabetes is characterized by elevated blood glucose levels, leading to an increased risk of cardiovascular diseases. Sodium butyrate, the sodium salt of the short-chain fatty acid butyric acid produced by gut microbiota fermentation, has shown promising effects on metabolic diseases, including type 2 diabetes and cardiovascular diseases. Sodium butyrate demonstrates anti-inflammatory, anti-oxidative, and lipid-lowering properties and can improve insulin sensitivity and reduce hepatic steatosis. In this review, we investigate how sodium butyrate influences cardiovascular complications of type 2 diabetes, including atherosclerosis (AS), heart failure (HF), hypertension, and angiogenesis. Moreover, we explore the pathophysiology of cardiovascular disease in type 2 diabetes, focusing on hyperglycemia, oxidative stress, inflammation, and genetic factors playing crucial roles. The review suggests that sodium butyrate can be a potential preventive and therapeutic agent for cardiovascular complications in individuals with type 2 diabetes.

Osteoarthritis (OA) is a progressive degenerative disease affected by many factors, and there is currently no effective treatment. In recent years, the latest progress in metabolomics in OA research has revealed several metabolic pathways and new specific metabolites involved in OA. Metabolites play significant roles in the identification and management of OA. This review looks back on the development history of metabolomics and the progress of this technology in OA as well as its potential clinical applications. It summarizes the applications of metabolites in the field of OA and future research directions. This understanding will advance the identification of metabolic treatment goals for OA.

The development of metabolomics offers possibilities for the treatment of OA. This article reviews the relationship between metabolites associated with chondrocytes and OA. Selectively altering these three metabolic pathways and their associated metabolites may hold great potential as new focal points for OA treatment.

Obesity is a multifactorial condition influenced by genetic, environmental, and microbiome-related factors. The gut microbiome plays a vital role in maintaining intestinal health, increasing mucus creation, helping the intestinal epithelium mend, and regulating short-chain fatty acid (SCFA) production. These tasks are vital for managing metabolism and maintaining energy balance. Dysbiosis-an imbalance in the microbiome-leads to increased appetite and the rise of metabolic disorders, both fuel obesity and its issues. Furthermore, childhood obesity connects with unique shifts in gut microbiota makeup. For instance, there is a surge in pro-inflammatory bacteria compared to children who are not obese. Considering the intricate nature and variety of the gut microbiota, additional investigations are necessary to clarify its exact involvement in the beginnings and advancement of obesity and related metabolic dilemmas. Currently, therapeutic methods like probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), dietary interventions like Mediterranean and ketogenic diets, and physical activity show potential in adjusting the gut microbiome to fight obesity and aid weight loss. Furthermore, the review underscores the integration of microbial metabolites with pharmacological agents such as orlistat and semaglutide in restoring microbial homeostasis. However, more clinical tests are essential to refine the doses, frequency, and lasting effectiveness of these treatments. This narrative overview compiles the existing knowledge on the multifaceted role of gut microbiota in obesity and much more, showcasing possible treatment strategies for addressing these health challenges.

Butyrate has been proposed as a drug therapy by acting as a lysine deacetylase (KDAC) inhibitor and elevating protein acetylation, in particular on histones. Nonetheless, recent studies suggest that tissues such as the gut can utilize butyrate as a metabolite. We have previously shown that the addition of butyrate induces a rapid increase of oxygen consumption in whole Drosophila melanogaster heads. Here we show that while head oxygen consumption is increased by the addition of butyrate, no apparent changes are observed on the proteome and acetylome. Instead, we show that butyrate is metabolized and incorporated into the tricarboxylic acid (TCA) cycle. Collectively our data supports the notion that the therapeutic benefits of acute butyrate treatment may be also mediated by improving metabolic rates, rather than solely targeting the epigenome or acetylome.

Cognitive dysfunction is an important comorbidity of type 2 diabetes mellitus (T2DM). Sodium butyrate (NaB) is a short-chain fatty acid and has an effect improving T2DM-associated cognitive dysfunction. Using a high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM mouse model, the present study investigated the mechanism involved in the beneficial effect of butyrate on diabetic cognitive dysfunction, with a focus on ameliorating mitochondrial damage through regulating the adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1α (AMPK/PGC-1α) pathway considering the important role of mitochondrial impairments in the occurrence of T2DM-associated cognitive dysfunction. We found, based on reconfirmation of the improvement of NaB on cognitive impairment, that NaB treatment improved damaged synaptic structural plasticity including the decrease in dendritic spine density and downregulation in the expression of postsynaptic density protein 95 and synaptophysin in the hippocampus in the model mice. NaB treatment also ameliorated mitochondrial ultrastructural damage, increased mitochondrial membrane potential and adenosine 5'-triphosphate content, and improved mitochondrial biogenesis and dynamics in the model mice. Furthermore, the expression of phosphorylated AMPK and PGC-1α was upregulated after NaB treatment in the model mice. In particular, the above beneficial effects of NaB were blocked by the inhibition of either AMPK or PGC-1α. In conclusion, NaB treatment improved cognitive impairment and damaged synaptic structural plasticity in the hippocampus by ameliorating damage to mitochondrial morphology and function through regulating the AMPK/PGC-1α pathway in HFD/STZ-induced T2DM mice.

The study will be to observe the effect of Sodium butyrate (NaB) on bone loss in lipopolysaccharide (LPS)-treated rats.

In the rat model, we observed that changes in the expression of oxidative stress regulators, inflammatory markers and target genes were measured by immunofluorescence and RT-PCR after treatment. Changes in viability and osteogenesis of MC3T3-E1, osteoclast differentiation in RAW264.7 cells in the presence of LPS were evaluated using CCK-8, ALP staining, RES staining, and TRAP staining.

In vitro experiments have shown that LPS-induced inhibition of JC-1, SIRT1, GPX1 and SOD2 is associated with increased levels of inflammation and oxidative stress. In addition, NaB has been found to suppress oxidative stress, inflammation and Mito SOX, promote osteogenic differentiation, and inhibit osteoclast differentiation. In addition, NaB significantly promoted SITR1 expression, repaired impaired bone metabolism, and improved bone strength and bone mineral density.

Given all this experimental evidence, the results strongly suggest that NaB can restore osteogenic activity in the presence of LPS by reducing intracellular ROS, inhibiting osteoclast differentiation and reducing bone loss in LPS-treated rat models.

With the advancement of metagenomics and metabolomics techniques, the crucial role of the gut microbiome in intestinal, cardiovascular, and metabolic disorders has been extensively explored. Vascular calcification (VC) is common in atherosclerosis, hypertension, diabetes mellitus, and chronic kidney disease. Moreover, it is a significant cause of cardiovascular diseases and mortality. Roseburia intestinalis, as a promising candidate for the next generation of probiotics, plays a substantial role in inhibiting the systemic inflammatory response and holds great potential in the treatment of intestinal diseases, cardiovascular diseases, and metabolic disorders. Its primary metabolite, butyrate, acts on specific receptors (GPR43, GPR41, GPR109a). It enters cells via transporters (MCT1, SMCT1), affecting gene expression through HDACs, PPARγ and Nrf2, promoting energy metabolism and changing the concentration of other metabolites (including AGEs, LPS, BHB) in the circulation to affect the body's life activities. In this paper, we focus on the possible mechanism of the primary metabolite butyrate of Roseburia intestinalis in inhibiting VC, which may become a potential therapeutic target for the treatment of VC and the ways to enhance its effect.

Butyric acid as a short-chain fatty acid (SCFA) is one of the key microbial metabolites of ruminants. Numerous studies indicate that butyrate is crucial in muscle growth and development, and plays an important molecular regulatory role mainly by inhibiting histone deacetylation. DNA methylation, a major epigenetic modification, is involved in cell differentiation. Butyrate, in addition to its role in acetylation modifications, can alter the DNA methylation status of cells. However, the impact of butyrate on the DNA methylation of bovine skeletal muscle satellite cells (SMSCs) remains unclear. In this study, we developed a differentiation model of SMSCs and employed RNA sequencing (RNA-seq) alongside whole genome bisulfite sequencing (WGBS) to explore the effects of butyrate treatment on DNA methylation status and its relationship with gene expression. Treatment of SMSCs with sodium butyrate (NaB) at 1.0 mM for 2 days significantly inhibited the expression of DNA methyltransferases (DNMT1, DNMT2, DNMT3A) at the mRNA and protein levels while promoting the expression of demethylases (TET1, TET2, TET3) at mRNA levels. WGBS identified 4292 differentially methylated regions (DMRs), comprising 2294 hypermethylated and 1998 hypomethylated regions. These DMRs were significantly enriched in the MAPK, cAMP, and Wnt signaling pathways, all of which are implicated in myogenesis and development. Combining RNA-seq and WGBS data revealed a total of 130 overlapping genes, including MDFIC, CREBBP, DMD, LTBP2 and KLF4. These genes are predominantly involved in regulating the FoxO, MAPK, PI3K-Akt, and Wnt signaling pathways. This study provides new insights into the effects of butyrate-mediated DNA methylation on SMSC development and enhances our understanding of butyrate as an epigenetic modifier beyond its role in acetylation.

This study provides a comprehensive assessment of how urban-rural divides influence gut microbial diversity and composition across the distinct geographical landscapes of Kazakhstan, elucidating the intricate interplay between lifestyle, environment, and gut microbiome. In this prospective cohort study, we enrolled 651 participants from urban centers and rural settlements across Kazakhstan, following ethical approval and informed consent. Comprehensive demographic, dietary, and stool sample data were collected. 16S rRNA gene sequencing and shotgun metagenomics techniques were employed to delineate the intricate patterns of the gut microbiome. A rigorous statistical framework dissected the interplay between urbanization gradients, geography, dietary lifestyles, and microbial dynamics. Our findings demonstrate a stark microbial divide between urban and rural gut ecosystems. The study found significant differences in gut microbiome diversity and composition between urban and rural populations in Kazakhstan. Urban microbiomes exhibited reduced diversity, higher Firmicutes/Bacteroidetes ratios, and increased prevalence of genera Coprococcus and Parasutterella. In contrast, rural populations had greater microbial diversity and abundance of Ligilactobacillus, Sutterella, and Paraprevotella. Urbanization also influenced dietary patterns, with urban areas consuming more salt, cholesterol, and protein, while rural areas had diets richer in carbohydrates and fiber. The study also identified distinct patterns in the prevalence of antibiotic resistance genes and virulence factors between urban and rural gut microbiomes. This study sheds light on how urbanization may be deeply involved in shaping the intricate mosaic of the gut microbiome across Kazakhstan's diverse geographical and dietary landscapes, underscoring the complex interplay between environmental exposures, dietary lifestyles, and the microbial residents inhabiting our intestines.

The study examined gut microbiome composition across diverse geographical locations in Kazakhstan, spanning urban centers and rural settlements. This allows for thoroughly investigating how urbanization gradients and geographic factors shape the gut microbiome. The study's examination of the gut resistome and prevalence of virulence-associated genes provide essential insights into the public health implications of urbanization-driven microbiome alterations. Collecting comprehensive demographic, dietary, and stool sample data enables the researchers to better understand the relationships between urbanization, nutritional patterns, and gut microbiome composition. The findings have important implications for understanding how urbanization-driven microbiome changes may impact human health and well-being, paving the way for tailored interventions to restore a balanced gut microbial ecology.

PM2.5 exposure has been found to cause gut dysbiosis and impair glucose homeostasis in human and animals, yet their underlying biological connection remain unclear. In the present study, we aim to investigate the biological significance of gut microbiota in PM2.5-induced glucose metabolic abnormalities. Our results showed that microbiota depletion by antibiotics treatment significantly alleviated PM2.5-induced glucose intolerance and insulin resistance, as indicated by the intraperitoneal glucose tolerance test, glucose-induced insulin secretion, insulin tolerance test, insulin-induced phosphorylation levels of Akt and GSK-3β in insulin sensitive tissues. In addition, faecal microbiota transplantation (FMT) from PM2.5-exposed donor mice successfully remodeled the glucose metabolism abnormalities in recipient mice, while the transplantation of autoclaved faecal materials did not. Faecal microbiota analysis demonstrated that the composition and alpha diversity of the gut bacterial community were altered by PM2.5 exposure and in FMT recipient mice. Furthermore, short-chain fatty acids levels analysis showed that the circulating acetate was significantly decreased in PM2.5-exposed donor and FMT recipient mice, and supplementation of sodium acetate for 3 months successfully improved the glucose metabolism abnormalities induced by PM2.5 exposure. These results indicate that manipulating gut microbiota or its metabolites could be a potential strategy for preventing the adverse health effects of ambient PM2.5.

Recent advances have led to greater recognition of the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD). There has been evidence that CKD is also associated with dysbiosis. Here, we aimed to evaluate whether probiotic supplements can have protective effects against kidney injury via improving mitochondrial function.

An animal model of CKD was induced by feeding C57BL/6 mice a diet containing 0.2% adenine. KBL409, a strain of Lactobacillus acidophilus, was administered via oral gavage at a dose of 1 × 109 CFU daily. To clarify the underlying mechanisms by which probiotics exert protective effects on mitochondria in CKD, primary mouse tubular epithelial cells stimulated with TGF-β and p-cresyl sulfate were administered with butyrate.

In CKD mice, PGC-1α and AMPK, key mitochondrial energy metabolism regulators, were down-regulated. In addition, mitochondrial dynamics shifted toward fission, the number of fragmented cristae increased, and mitochondrial mass decreased. These alterations were restored by KBL409 administration. KBL409 supplementation also improved defects in fatty acid oxidation and glycolysis and restored the suppressed enzyme levels involved in TCA cycle. Accordingly, there was a concomitant improvement in mitochondrial respiration and ATP production assessed by mitochondrial function assay. These favorable effects of KBL409 on mitochondria ultimately decreased kidney fibrosis in CKD mice. In vitro analyses with butyrate recapitulated the findings of animal study.

This study demonstrates that administration of the probiotic Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function.

The human gut microbiota is increasingly recognized as a pivotal factor in diabetes management, playing a significant role in the body's response to treatment. However, it is important to understand that long-term usage of medicines like metformin and other diabetic treatments can result in problems, gastrointestinal discomfort, and dysbiosis of the gut flora. Advanced sequencing technologies have improved our understanding of the gut microbiome's role in diabetes, uncovering complex interactions between microbial composition and metabolic health. We explore how the gut microbiota affects glucose metabolism and insulin sensitivity by examining a variety of -omics data, including genomics, transcriptomics, epigenomics, proteomics, metabolomics, and metagenomics. Machine learning algorithms and genome-scale modeling are now being applied to find microbiological biomarkers associated with diabetes risk, predicted disease progression, and guide customized therapy. This study holds promise for specialized diabetic therapy. Despite significant advances, some concerns remain unanswered, including understanding the complex relationship between diabetes etiology and gut microbiota, as well as developing user-friendly technological innovations. This mini-review explores the relationship between multiomics, precision medicine, and machine learning to improve our understanding of the gut microbiome's function in diabetes. In the era of precision medicine, the ultimate goal is to improve patient outcomes through personalized treatments.

Milk and its derivatives are included in a balanced diet of humans as excellent sources of proteins, vitamins, and essential minerals that are functional nutrients. Knowledge about the nutritional benefits or harms due to milk consumption has been expanding in recent years. We previously explored, in rodent models, the metabolic effects of isoenergetic intake of milk derived from cows, donkeys, or humans, while the impact of goat's milk intake has remained unexplored. The aim of this work was to investigate, in an animal model, the effects of dietary supplementation with goat's milk on energy homeostasis and inflammatory state, focusing on the modulation of mitochondrial functions in most metabolically active organs, such as skeletal muscle and the liver. In addition, we highlighted a link between nutrient intake, substrate metabolism, and the orexinergic system. Our results indicate that goat milk improves mitochondrial oxidative capacity and reduces inflammation and oxidative stress in both organs. Notably, goat milk lowers the circulating levels of Orexin-A, a neuropeptide that plays a crucial role in regulating peripheral energy balance and central nervous system mechanisms. These data provide the first evidence that the anti-inflammatory and antioxidant effects of goat milk are mediated by the modulation of mitochondrial functions and orexinergic signaling.

Among the non-communicable neurological diseases, epilepsy is characterized by abnormal brain activity with several peripheral implications. The role of peripheral inflammation in the relationship between seizure development and nonalcoholic fatty liver disease based on sex difference remains still overlooked. Severe early-life infections lead to increased inflammation that can aggravate epilepsy and hepatic damage progression, both related to increased odds of hospitalization for epileptic patients with liver diseases. Here, we induced a post-natal-day 3 (PND3) infection by LPS (1 mg/kg, i.p.) to determine the hepatic damage in a genetic model of young epileptic WAG/Rij rats (PND45). We evaluated intra- and inter-gender differences in systemic and liver inflammation, hepatic lipid dysmetabolism, and oxidative damage related to mitochondrial functional impairment. First, epileptic rats exposed to LPS, regardless of gender, displayed increased serum hepatic enzymes and altered lipid profile. Endotoxin challenge triggered a more severe inflammatory and immune response in male epileptic rats, compared to females in both serum and liver, increasing pro-inflammatory cytokines and hepatic immune cell recruitment. Conversely, LPS-treated female rats showed significant alterations in systemic and hepatic lipid profiles and reduced mitochondrial fatty acid oxidation. The two different sex-dependent mechanisms of LPS-induced liver injury converge in increased ROS production and related mitochondrial oxidative damage in both sexes. Notably, a compensatory increase in antioxidant defense was evidenced only in female rats. Our study with a translational potential demonstrates, for the first time, that early post-natal infections in epileptic rats induced or worsened hepatic disorders in a sex-dependent manner, amplifying inflammation, lipid dysmetabolism, and mitochondrial impairment.

Metabolic syndrome refers to the pathological state of metabolic disorder of protein, fat, carbohydrate, and other substances in the human body. It is a syndrome composed of a group of complex metabolic disorders, whose pathogenesis includes multiple genetic and acquired entities falling under the category of insulin resistance and chronic low-grade inflammationand. It is a risk factor for increased prevalence and mortality from diabetes and cardiovascular disease. Cardiovascular diseases are the predominant cause of morbidity and mortality globally, thus it is imperative to investigate the impact of metabolic syndrome on alleviating this substantial disease burden. Despite the increasing number of scientists dedicating themselves to researching metabolic syndrome in recent decades, numerous aspects of this condition remain incompletely understood, leaving many questions unanswered. In this review, we present an epidemiological analysis of MetS, explore both traditional and novel pathogenesis, examine the pathophysiological repercussions of metabolic syndrome, summarize research advances, and elucidate the mechanisms underlying corresponding treatment approaches.

The various roles of the mitochondria and the microbiome in health and disease have been thoroughly investigated, though they are often examined independently and in the context of chronic disease. However, the mitochondria and microbiome are closely connected, namely, through their evolution, maternal inheritance patterns, overlapping role in many diseases and their importance in the maintenance of human health. The concept known as the "mitochondria-microbiome crosstalk" is the ongoing bidirectional crosstalk between these two entities and warrants further exploration and consideration, especially in the context of primary mitochondrial disease, where mitochondrial dysfunction can be detrimental for clinical manifestation of disease, and the role and composition of the microbiome is rarely investigated. A potential mechanism underlying this crosstalk is the role of metabolites from both the mitochondria and the microbiome. During digestion, gut microbes modulate compounds found in food, which can produce metabolites with various bioactive effects. Similarly, mitochondrial metabolites are produced from substrates that undergo biochemical processes during cellular respiration. This review aims to provide an overview of current literature examining the mitochondria-microbiome crosstalk, the role of commonly studied metabolites serve in signaling and mediating these biochemical pathways, and the impact diet has on both the mitochondria and the microbiome. As a final point, this review highlights the up-to-date implications of the mitochondria-microbiome crosstalk in mitochondrial disease and its potential as a therapeutic tool or target.

Metabolic syndrome (MetS) as a multifactorial disorder is associated with non-communicable diseases. The dietary approaches to stop hypertension (DASH) diet is a healthy dietary pattern. We investigated the effect of the DASH diet on fatty liver and cardiovascular risk factors in subjects with MetS.

60 Subjects with MetS were assigned into the intervention group (DASH diet) or the control group (a healthy diet). Fatty liver index (FLI), hepatic steatosis index (HSI), waist circumference (WC), weight, body mass index (BMI), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) were evaluated at the beginning and after intervention. Equations of fatty liver indices such as FLI and HSI are based on liver enzymes, anthropometric variables, sex and having diabetes.

30 subjects in the intervention group and 29 subjects in the control group completed the study. We found a significant reduction in the intervention group compared to the control group in FLI (-13.06 ± 10.03 vs. -2.90 ± 6.82;P < 0.001), HSI (-2.72 ± 2.59 vs. -0.81 ± 3.80;P = 0.02), WC (-6.02 ± 4.24 vs. -2.24 ± 4.28;P = 0.001), weight (-3.39 ± 2.53 vs. -1.51 ± 2.72;P = 0.008), BMI (-1.25 ± 0.93 vs. -0.56 ± 1.01;P = 0.008), DBP (-5.16 ± 3.92 vs. -1.50 ± 7.04;P = 0.01), SBP (-6.97 ± 8.21 vs. -1.36 ± 6.83;P = 0.006), TG (-18.50 ± 14.32 vs. 0.60 ± 23.81;P < 0.001), TC (-16.10 ± 17.94 vs. -5.07 ± 23.62;P = 0.04) and LDL-c (-13.50 ± 9.58 vs. -4.90 ± 18.28;P = 0.02). These results remained significant after adjusting for confounding factors, except for TC (P = 0.25).

The DASH diet was more effective than the control diet in managing fatty liver and cardiovascular risk factors.

The trial was registered on 21 October 2022 at Iranian Registry of Clinical Trials (IRCT20180201038585N12, URL: https://irct.behdasht.gov.ir/trial/66161 ).

Hepatobiliary malignancies, which include hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are the sixth most common cancers and the third leading cause of cancer-related death worldwide. Hepatic carcinogenesis is highly stimulated by chronic inflammation, defined as fibrosis deposition, and an aberrant imbalance between liver necrosis and nodular regeneration. In this context, the gut-liver axis and gut microbiota have demonstrated a critical role in the pathogenesis of HCC, as dysbiosis and altered intestinal permeability promote bacterial translocation, leading to chronic liver inflammation and tumorigenesis through several pathways. A few data exist on the role of the gut microbiota or bacteria resident in the biliary tract in the pathogenesis of CCA, and some microbial metabolites, such as choline and bile acids, seem to show an association. In this review, we analyze the impact of the gut microbiota and its metabolites on HCC and CCA development and the role of gut dysbiosis as a biomarker of hepatobiliary cancer risk and of response during anti-tumor therapy. We also discuss the future application of gut microbiota in hepatobiliary cancer management.