Excessive intake of dietary fats is strongly associated with an increased risk of various chronic diseases, such as obesity, diabetes, hepatic metabolic disorders, cardiovascular disease, chronic intestinal inflammation, and certain cancers. A significant portion of the adverse effects of high-fat diet on disease risk is mediated through modifications in the gut microbiota. Specifically, high-fat diets are linked to reduced microbial diversity, an overgrowth of gram-negative bacteria, an elevated Firmicutes-to-Bacteroidetes ratio, and alterations at various taxonomic levels. These microbial alterations influence the intestinal metabolism of small molecules, which subsequently increases intestinal permeability, exacerbates inflammatory responses, disrupts metabolic functions, and impairs signal transduction pathways in the host. Consequently, diet-induced changes in the gut microbiota play a crucial role in the initiation and progression of chronic diseases. This review explores the relationship between high-fat diets and gut microbiota, highlighting their roles and underlying mechanisms in the development of chronic metabolic diseases. Additionally, we propose probiotic interventions may serve as a promising adjunctive therapy to counteract the negative effects of high-fat diet-induced alterations in gut microbiota composition.

This review explores the emerging term "gut-skin axis" (GSA), describing the bidirectional signaling that occurs between the skin and the gastrointestinal tract under both homeostatic and disease conditions. Central to GSA communication are the gut and skin microbiota, the microbial communities that colonize these barrier surfaces. By influencing diverse host pathways, including innate immune, vitamin D receptor, and Aryl hydrocarbon receptor signaling, a balanced microbiota contributes to both tissue homeostasis and host defense. In contrast, microbiota imbalance, or dysbiosis at one site, can lead to local barrier dysfunction, resulting in the activation of signaling pathways that can disrupt tissue homeostasis at the other site, potentially leading to inflammatory skin conditions such as atopic dermatitis and psoriasis, or gut diseases like Inflammatory Bowel Disease. To date, most research on the GSA has examined the impact of the gut microbiota and diet on skin health, but recent studies show that exposing the skin to ultraviolet B-light can beneficially modulate both the gut microbiome and intestinal health. Thus, despite the traditional focus of clinicians and researchers on these organ systems as distinct, the GSA offers new opportunities to better understand the pathogenesis of cutaneous and gastrointestinal diseases and promote health at both sites.

Cancer is a long-term illness that involves an imbalance in cellular and immune functions. It can be caused by a range of factors, including exposure to environmental carcinogens, poor diet, infections, and genetic alterations. Maintaining a healthy gut microbiome is crucial for overall health, and short-chain fatty acids (SCFAs) produced by gut microbiota play a vital role in this process. Recent research has established that alterations in the gut microbiome led to decreased production of SCFA's in lumen of the colon, which associated with changes in the intestinal epithelial barrier function, and immunity, are closely linked to colorectal cancer (CRC) development and its progression. SCFAs influence cancer progression by modifying epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNA functions thereby affecting tumor initiation and metastasis. This suggests that restoring SCFA levels in colon through microbiota modulation could serve as an innovative strategy for CRC prevention and treatment. This review highlights the critical relationship between gut microbiota and CRC, emphasizing the potential of targeting SCFAs to enhance gut health and reduce CRC risk.

Gut microbiota dysbiosis induced by antibiotic use weakens its colonization resistance against opportunistic pathogens, increasing the risk of invasion and infection. While probiotics have the potential to restore the impaired gut microbial structure and prevent respiratory tract infections, the effectiveness of specific strains and the underlying mechanisms remain largely unexplored. In this study, the preventive effects of a novel butyrate-producing bacterium, Clostridium cellabutyricum YQ-FP-027T against Pseudomonas aeruginosa infection after antibiotic exposure were investigated in antibiotic-pretreated mice model.

Phenotypic characterizations including the bacterial load in the lung, the assessment of gene expression of immune factors in lung tissue using qPCR, and detection of gut microbial composition using 16S rRNA sequencing were conducted. Pulmonary bacterial load and expression levels of immune factors of lung tissue, and gut microbial composition were evaluated.

Our results demonstrated that YQ-FP-027T ameliorated lung tissue integrity, significantly reduced pulmonary bacterial burden, and decreased the expression of interleukin-1β and TNF-α, while enhancing the expression of interleukin-10 and cathelicidin-related antimicrobial peptide. Furthermore, YQ-FP-027T increased the abundance of Lachnospiraceae in the gut and reduced the abundance of opportunistic pathogens such as Enterococcaceae and Helicobacteraceae.

These results suggest YQ-FP-027T exerts probiotic effects by restoring gut microbiota balance, enhancing intestinal barrier function, and positively influencing pulmonary immune responses through the gut-lung axis. This study reveals the preventive potential of YQ-FP-027T against P. aeruginosa infection in the context of gut microbiota dysbiosis, offering a novel preventive strategy.

Although preclinical data support the hypothesis that butyric acid supplementation improves kidney health, the clinical significance of dietary butyric acid intake in patients with chronic kidney disease (CKD) remains unconfirmed in large-sample studies. This study aimed to investigate the association between dietary butyric acid intake and all-cause mortality in the United States population, stratified by kidney function.

We examined the relationship between dietary butyric acid intake, assessed through a 24-h dietary recall, and all-cause mortality among 23,008 consecutive adult participants from the National Health and Nutrition Examination Surveys (NHANES, 2005-2018), categorized by impaired versus normal kidney function (estimated glomerular filtration rate <60 vs ≥ 60 mL/min/1.72 m2), using multivariable Cox models. We also employed a restricted cubic spline based on Cox regression models to elucidate the nonlinear relationship between dietary butyric acid intake and mortality in patients.

In participants with impaired kidney function, high dietary butyric acid intake was associated with lower mortality, while lower intake levels (reference) showed no such association: adjusted HRs (aHRs) were 0.67 (95 % CI: 0.45, 1.00), 0.65 (95 % CI: 0.45, 0.94), and 0.58 (95 % CI: 0.38, 0.89) for intake levels of the square root of butyric acid 0.25-0.45, 0.45-0.75, and >0.75 g/day, respectively. However, in participants with normal kidney function, no association between butyric acid levels and mortality was observed. Additionally, we identified an L-shaped association between the levels of the square root of dietary butyric acid intake and all-cause mortality in the CKD population, reaching a plateau at 0.52 g/day (butyric acid intake of approximately 0.27 g/day).

This study revealed a nonlinear association between high dietary butyric acid intake and reduced all-cause mortality in patients with chronic kidney disease. A plateau occurs after 0.27 g/day, and for individuals with CKD whose butyric acid intake is below approximately 0.27 g/day, increasing a butyrate-rich diet or supplementing with butyric acid preparations may help prevent progression to renal failure and associated adverse outcomes in CKD patients, thereby reducing mortality. Therefore, it can be considered a new therapeutic strategy for the treatment of chronic kidney disease.

Butyrate is one of major metabolites of periodontitis-associated bacteria and often detected in periodontal pockets. Butyrate has been considered to affect human gingival fibroblasts (HGFs); however, there was no information on its long-term effect as occurs in periodontitis. Therefore, this study aimed to evaluate the time-dependent effects of butyrate on HGFs.

The effects of butyrate on HGF proliferation, apoptosis, cell morphology, glucose metabolic activity, butyrate metabolic activity, and cell migration ability were evaluated by cell counting, DNA electrophoresis, cell staining, pH-stat system, HPLC, and scratch test, respectively.

HGF proliferation was temporarily inhibited by 5-10 mM butyrate (p < 0.05); however, it resumed at 24 h with morphological changes from spindle to slightly widened (p < 0.05). HGFs cultured with 10 mM butyrate for 12-24 h shifted the glucose metabolic pathway from oxidative phosphorylation to glycolysis (p < 0.05), and increased butyrate consumption, which returned to control levels over 24 h. HGF migration ability tended to decrease at 72 h.

HGF cell proliferation and glucose/butyrate metabolism were temporarily inhibited by butyrate and then recovered in a time-dependent manner, accompanied by changes in cell morphology. These time-dependent effects may help to understand the role of butyrate in the pathology of periodontitis.

Atherosclerosis (AS) remains a leading cause of cardiovascular disease and mortality globally. This chronic condition is characterized by inflammation, lipid accumulation, and the deposition of cellular components within arterial walls. Emerging evidence has highlighted the multifaceted therapeutic potential of short-chain fatty acids (SCFAs) in mitigating AS progression. SCFAs have demonstrated anti-inflammatory properties and the ability to regulate immune responses, metabolic pathways, vascular integrity, and intestinal barrier function in animal models of AS. Consequently, SCFAs have garnered significant attention as a promising approach for the prevention and treatment of AS. However, further clinical trials and studies are necessary to fully elucidate the underlying mechanisms and effects of SCFAs. Additionally, different types of SCFAs may exert distinct impacts, necessitating more in-depth investigation into their specific roles and mechanisms. This review provides an overview of the diverse cellular mechanisms contributing to AS formation, as well as a discussion of the significance of SCFAs in AS pathogenesis and their multifaceted therapeutic potential. Nonetheless, additional research is warranted to comprehensively understand and harness the potential of various SCFAs in the context of AS.

Necrotic enteritis (NE) in broiler chickens leads to significant economic losses in poultry production. This study examined the inhibitory effects of usnic acid and tannic acid on coccidia, sporozoite, and Clostridium perfringens and assessed their influence on growth performance and intestinal health in NE-challenged broilers through in vitro and in vivo experiments.

The in vitro experiment included 5 treatment groups: the negative control (NC), 2 μmol/L diclazuril (DZ), 30 μmol/L usnic acid (UA), 90 μmol/L tannic acid (TA), and 15 μmol/L usnic acid + 45 μmol/L tannic acid (UTA) groups. The in vivo experiment involved 320 broilers divided into four groups: PC (NE-challenged), SA (500 mg/kg salinomycin premix + NE-challenged), UA (300 mg/kg usnic acid + NE-challenged), and UTA (300 mg/kg usnic acid + 500 mg/kg tannic acid + NE-challenged) groups.

In the in vitro study, the UA, TA, and UTA treatments significantly increased apoptosis in coccidian oocysts and sporozoites, lowered the mitochondrial membrane potential (P < 0.05), and disrupted the oocyst structure compared with those in the NC group. UA and TA had inhibitory effects on C. perfringens, with the strongest inhibition observed in the UTA group. The in vivo results demonstrated that the SA group presented significantly improved growth performance on d 13, 21, and 28 (P < 0.05), whereas the UA and UTA groups presented improvements on d 13 and 21 (P < 0.05). The SA, UA, and UTA treatments reduced the intestinal lesion scores by d 28 and the fecal coccidian oocyst counts from d 19 to 21 (P < 0.05). Compared with the PC group, the UA and UTA groups presented lower intestinal sIgA levels and CD8+ cell percentages (P < 0.05), with a trend toward a reduced CD3+ cell percentage (P = 0.069). The SA, UA, and UTA treatments significantly reduced the serum diamine oxidase activity, crypt depth, and platelet-derived growth factor levels in the intestinal mucosa while increasing the villus height to crypt depth ratio and number of goblet cells (P < 0.05). The UTA treatment also significantly increased the acetate and butyrate concentrations in the cecum (P < 0.05). With respect to the gut microbiota, significant changes in β diversity in the ileum and cecum were observed in the SA, UA, and UTA groups, indicating that the microbial community compositions differed among the groups. Romboutsia dominated the SA group, Bacillales dominated the UA group, and Lactobacillales and Lachnospirales dominated the UTA group in the ileal microbiota. In the cecal microbiota, Lactobacillus, Butyricicoccus, and Blautia abundances were significantly elevated in the UTA group (P < 0.05).

Usnic acid and tannic acid induce apoptosis in coccidia and sporozoites by lowering the mitochondrial membrane potential. Both usnic acid alone and in combination with tannic acid alleviate NE-induced adverse effects in broilers by modulating intestinal immunity, altering the microbial composition, and improving intestinal barrier function. Compared with usnic acid alone, the combination of usnic acid and tannic acid had superior effects, providing a promising basis for the development of effective feed additive combinations.

Inflammatory Bowel Disease (IBD) is a complex intestinal disorder that typically triggers inflammatory responses, immune dysregulation, and gut microbiota imbalance. Lignoformic acid (LFA) is a lignin-derived compound containing benzene rings and hydroxyl functional groups. It has antioxidant properties and can regulate intestinal pH. This study aimed to investigate the improve effects of LFA on dextran sulfate sodium (DSS)-induced chronic colitis in mice. The results showed that LFA treatment significantly improved body weight and Disease Activity Index (DAI) in mice and alleviated colon damage. In terms of oxidative stress and anti-inflammatory effects, the expression of antioxidant enzymes such as Glutathione Peroxidase (GSH-PX) and Superoxide Dismutase (SOD) was dose-dependently enhanced in DSS-induced mice. LFA reduced the expression of Tumor Necrosis Factor-alpha (TNF-α) by modulating the TLR4/MyD88/NF-κB signaling pathway. Furthermore, LFA dose-dependently increased the abundance of beneficial bacteria, including Akkermansia and Lachnospiraceae, and promoted the production of short-chain fatty acids (SCFAs). These findings suggest that LFA could serve as a therapeutic agent for colitis by enhancing intestinal barrier integrity, regulating inflammation, and restoring gut microbiota balance.

The intestinal tract, a complex organ responsible for nutrient absorption and digestion, relies heavily on a balanced gut microbiome to maintain its integrity. Disruptions to this delicate microbial ecosystem can lead to intestinal inflammation, a hallmark of inflammatory bowel disease (IBD). While the role of the gut microbiome in IBD is increasingly recognized, the underlying mechanisms, particularly those involving endoplasmic reticulum (ER) stress, autophagy, and cell death, remain incompletely understood. ER stress, a cellular response to various stressors, can trigger inflammation and cell death. Autophagy, a cellular degradation process, can either alleviate or exacerbate ER stress-induced inflammation, depending on the specific context. The gut microbiome can influence both ER stress and autophagy pathways, further complicating the interplay between these processes. This review delves into the intricate relationship between ER stress, autophagy, and the gut microbiome in the context of intestinal inflammation. By exploring the molecular mechanisms underlying these interactions, we aim to provide a comprehensive theoretical framework for developing novel therapeutic strategies for IBD. A deeper understanding of the ER stress-autophagy axis, the gut microbial-ER stress axis, and the gut microbial-autophagy axis may pave the way for targeted interventions to restore intestinal health and mitigate the impact of IBD.

Liver transplantation (LT) is the ultimate treatment for patients with end-stage liver disease or early hepatocellular carcinoma. In the context of LT, because of the unique immunological characteristics of human liver allograft, 5%-20% of selected LT recipients can achieve operational tolerance. Nonetheless, there remains a risk of rejection in LT patients. Maintaining immune homeostasis is thus crucial for improving clinical outcomes in these patients. In mechanism, several immune cells, including dendritic cells, Kupffer cells, myeloid-derived suppressor cells, hepatic stellate cells, regulatory B cells, and CD4 + regulatory T cells (Treg), contribute to achieving tolerance following LT. In terms of Treg, it plays a role in successfully minimizing immunosuppression or achieving tolerance post-LT while also reducing the risk of rejection. Furthermore, the gut microbiome modulates systemic immune functions along the gut-liver axis. Recent studies have explored changes in the microbiome and its metabolites under various conditions, including post-LT, acute rejection, and tolerance. Certain functional microbiomes and metabolites exhibit immunomodulatory functions, such as the augmentation of Treg, influencing immune homeostasis. Therefore, understanding the mechanisms of tolerance in LT, the role of Treg in tolerance and rejection, as well as their interactions with gut microbiome, is vital for the management of LT patients.

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.

Crohn's disease (CD) and ulcerative colitis (UC) are the two major entities of inflammatory bowel disease (IBD). These disorders are known for their relapsing disease course and severe gastrointestinal symptoms including pain, diarrhoea and bloody stool. Accumulating evidence suggests that IBD is not only restricted to the gastrointestinal tract and that disease processes are able to reach distant organs including the brain. In fact, up to 35 % of IBD patients also suffer from neuropsychiatric disorders such as generalized anxiety disorder and major depressive disorder. Emerging research in this area indicates that in many cases these neuropsychiatric disorders are a secondary condition as a consequence of the disturbed communication between the gut and the brain via the microbiota-gut-brain axis. In this review, we summarise the current knowledge on IBD-associated neuropsychiatric disorders. We examine the role of different pathways of the microbiota-gut-brain axis in the development of CNS disorders highlighting altered neural, immunological, humoral and microbial communication. Finally, we discuss emerging therapies targeting the microbiota-gut-brain axis to alleviate IBD and neuropsychiatric symptoms including faecal microbiota transplantation, psychobiotics, microbial metabolites and vagus nerve stimulation.

Gut microbiota play an influential role in how animals adapt to extreme environments. Two phylogenetically distant mammals, Yunnan snub-nosed monkey and reindeer both adapted to frigid environments. Metagenomic analyses revealed they developed similar cold adaptation strategies in response to food scarcity (enhanced fiber degradation and nitrogen balance maintenance), energy shortages (increased short-chain fatty acid [SCFA] synthesis), and a constant body temperature sustainment (stimulation of non-shivering thermogenesis [NST]). Moreover, they evolved distinct adaptation strategies to cope with different cold ecosystems. Yunnan snub-nosed monkey adapt to high-altitude hypoxia environment through enhancing ability to synthesize lactate and metabolize purine, while reindeer adapt to extreme cold environment through increasing blood flow, strengthening urea cycling, and enriching fat storage associated bacteria. Notably, reindeer microbiota uniquely enriched cholesterol-degrading bacteria, potentially mitigating cardiovascular risks from lipid storage. Our study expands the knowledge of how gut microbiome promotes cold adaptation through shared and specialized mechanisms shaped by different phylogenetic and ecological contexts.

The objective of this study was to investigate the effects of fermented wheat bran (FWB) on growth performance, nutrient digestibility, serum biochemistry, short-chain fatty acids, and intestinal microbiota of weaned piglets. One hundred twenty-eight weaned piglets were randomly assigned to 4 groups, each with 8 pens and 4 piglets per pen: basal diet group (BD), 5% wheat bran group (5% WB), 5% fermented wheat bran group (5% FWB), and 10% fermented wheat bran group (10% FWB) for a 28-day trial. Results showed that compared to the BD group, the diarrhea rate in the 5% WB group was significantly increased (p < 0.05) at d 15-28 and d 1-28. In contrast, at d 15-28 and d 1-28, the diarrhea rates in the 5% FWB and 10% FWB groups were significantly lower than those in the 5% WB group and showed no significant difference compared to the BD group. Moreover, the apparent total tract digestibility (ATTD) of DM, GE, CP, EE, CF and ADF at d 1-14, and EE and NDF at d 15-28 in the 5% FWB group were significantly improved compared to the 5% WB group (p < 0.05). However, only the ATTD of CP, EE and CF at d 1-14 in the 10% FWB group were significantly higher than those in the 5% WB group (p < 0.01). Compared to the BD group, the pH of cecum chyme and serum urea nitrogen content in the 5% FWB and 10% FWB groups were significantly reduced (p < 0.05), and those in the 10% FWB group were significantly lower than those in the 5% WB group (p < 0.01). The propionic acid content of cecum chyme in the 5% FWB and 10% FWB groups, and butyric acid content in the 10% FWB group were significantly higher than those in the BD group (p < 0.05). LEfSe analysis (LDA score > 3.0) identified 4 species, 6 species of Proteobacteria, 2 species, and 9 species that were enriched in the BD, 5% WB, 5%F WB and 10%F WB groups, respectively. Additionally, Dialister, Prevotellaceae_NK3B31_group, Mitsuokella, Succinivibrio, and Prevotella were significantly and positively correlated with the concentrations of valeric acid, propionic acid, and acetic acid (p < 0.05). In conclusion, 10% FWB supplementation in weaned piglet diets did not affect growth performance, it reduced the diarrhea rate compared to the 5% WB group, potentially due to enhanced nutrient digestibility, elevated SCFAs levels, and shifts in microbial composition.

China's equine industry has shifted from traditional rough grazing to modern intensive farming, expanding the roles of horses into eventing, leisure, tourism, and meat and dairy production. Concurrently, equine nutrition has evolved from a forage-based diet to a more diverse regimen incorporating grain supplements to meet the heightened energy demands of intensive farming. However, nutrient digestibility and glycemic response vary considerably based on grain type, starch content, composition, and structural properties. Optimal grain selection is therefore essential for energy supplementation across developmental stages to sustain growth and performance. This study examines the impact of diets incorporating steam-flaked grains (corn, oats, and barley) on apparent nutrient digestibility, glycemic response, and fecal volatile fatty acid (VFA) composition in the weaned Kazakh foals.

Eighteen male Kazakh foals, weaned at 5 months, were randomly assigned to three groups (n = 6 per group) based on grain type: corn group (CG), oats group (OG), and barley group (BG). The daily starch intake for the foals was set at 2 g starch (DM)/kg body weight per day to determine the amount of concentrate supplements to be fed, based on the principle of equal grain starch intake over a 60-day feeding trial.

Results indicated that the apparent nutrient digestibility was lower in OG than in CG and BG (P > 0.05). However, amylose intake and digestibility were significantly higher in OG compared to CG (P < 0.01). Plasma glucose and glucagon levels were elevated in CG relative to OG and BG (P < 0.01), while the insulin/glucose ratio was highest in the BG. Additionally, BG increased fecal lactic acid and total VFA (TVFA) concentrations while reducing fecal pH.

For weaned Kazakh foals, steam-flaked corn could be recommended in advance of steam-flaked oats and barley in cereal-based energy supplementation alongside basal forage diets. It may reduce amylose intake, improve glycemic responses, increase plasma glucose levels and reduce fecal lactic acid content.

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by joint inflammation and skin lesions. Recent research has underscored the critical role of gut microbiota-comprising bacteria, fungi, viruses, and archaea-in the pathogenesis and progression of PsA. This narrative review synthesizes the latest findings on the influence of gut microbiota on PsA, focusing on mechanisms such as immune modulation, microbial dysbiosis, the gut-joint axis, and its impact on treatment. Advances in high-throughput sequencing and metagenomics have revealed distinct microbial profiles associated with PsA. Studies show that individuals with PsA have a unique gut microbiota composition, differing significantly from healthy controls. Alterations in the abundance of specific bacterial taxa, including a decrease in beneficial bacteria and an increase in potentially pathogenic microbes, contribute to systemic inflammation by affecting the intestinal barrier and promoting immune responses. This review explores the impact of various factors on gut microbiota composition, including age, hygiene, comorbidities, and medication use. Additionally, it highlights the role of diet, probiotics, and fecal microbiota transplantation as promising strategies to modulate gut microbiota and alleviate PsA symptoms. The gut-skin-joint axis concept illustrates how gut microbiota influences not only gastrointestinal health but also skin and joint inflammation. Understanding the complex interplay between gut microbiota and PsA could lead to novel, microbiome-based therapeutic approaches. These insights offer hope for improved patient outcomes through targeted manipulation of the gut microbiota, enhancing both diagnosis and treatment strategies for PsA.

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.

Background: This review explores the impact of gut microbiota profiles in predicting the response to anti-integrin biologic therapy, particularly vedolizumab, in inflammatory bowel disease (IBD) patients. IBD, encompassing Crohn's disease and ulcerative colitis, is a chronic inflammatory condition with a growing prevalence linked to industrialization and lifestyle changes. Disruption in the gut microbiota balance, characterized by reduced diversity and altered short-chain fatty acid (SCFA) production, is associated with IBD and its symptoms. Current pharmacological treatments target healing and remission, with vedolizumab offering a gut-selective treatment approach. Methods: A search of the literature was performed on the relationship between anti-integrin treatment and the microbiome profile in IBD. Articles were examined from the PubMed, Medline, Cochrane, and Web of Science databases. Results: This review identified five human studies investigating the relationship between gut microbiome composition, SCFAs, and response to vedolizumab, revealing an increased abundance of beneficial bacteria and levels of SCFAs like butyrate in remission cases. Despite promising findings, the small sample sizes and limited scope of the existing studies highlight the need for larger, comprehensive research. Conclusions: This review underscores the potential of gut microbiome and metabolite profiling as non-invasive biomarkers for IBD severity and treatment outcomes, advocating for personalized therapeutic strategies to enhance efficacy. The insights gained could lead to novel diagnostic and treatment modalities, although further validation is necessary to fully understand the intricate connections between gut microbiota and IBD prognosis.

Plants are composed of diverse secondary metabolites (PSMs), which are widely associated with human health. Whether and how the gut microbiome mediates such impacts of PSMs is poorly understood. Here, we show that discrete dietary and medicinal phenolic glycosides, abundant health-associated PSMs, are utilized by distinct members of the human gut microbiome. Within the Bacteroides, the predominant gram-negative bacteria of the Western human gut, we reveal a specialized multi-enzyme system dedicated to the processing of distinct glycosides based on structural differences in phenolic moieties. This Bacteroides metabolic system liberates chemically distinct aglycones with diverse biological functions, such as colonization resistance against the gut pathogen Clostridioides difficile via anti-microbial activation of polydatin to the stilbene resveratrol and intestinal homeostasis via activation of salicin to the immunoregulatory aglycone saligenin. Together, our results demonstrate generation of biological diversity of phenolic aglycone "effector" functions by a distinct gut-microbiome-encoded PSM-processing system.

This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.

Aging is accompanied by considerable changes in the gut microbiome, yet the molecular mechanisms driving aging and the role of the microbiome remain unclear. Here we combined metagenomics, transcriptomics and metabolomics from aging mice with metabolic modelling to characterize host-microbiome interactions during aging. Reconstructing integrated metabolic models of host and 181 mouse gut microorganisms, we show a complex dependency of host metabolism on known and previously undescribed microbial interactions. We observed a pronounced reduction in metabolic activity within the aging microbiome accompanied by reduced beneficial interactions between bacterial species. These changes coincided with increased systemic inflammation and the downregulation of essential host pathways, particularly in nucleotide metabolism, predicted to rely on the microbiota and critical for preserving intestinal barrier function, cellular replication and homeostasis. Our results elucidate microbiome-host interactions that potentially influence host aging processes. These pathways could serve as future targets for the development of microbiome-based anti-aging therapies.

Ulcerative colitis (UC) is a long-term inflammatory bowel disease characterized by intense inflammation of the colorectal mucosa. Overproduction of reactive oxygen species exacerbates the progression of UC, which is linked to mitochondrial impairment and dysbiosis of the intestinal microbiota. CaGA nanozymes have demonstrated efficacy in the treatment of UC. The modulation of M1 and M2 polarization of macrophages by CaGA nanozymes has been demonstrated to be useful in reducing inflammation. Furthermore, CaGA nanozymes regulate the M1 and M2 polarization of macrophages, efficiently decreasing inflammation. The oral delivery of CaGA nanozymes resulted in their enrichment in inflamed areas of the colon and effectively reduced colonic damage in mice with DSS-induced colitis by improving the repair of the intestinal barrier. An investigation of 16S rDNA sequencing revealed that CaGA nanozymes regulate populations of both pathogenic and helpful bacteria and impact the progression of ulcerative colitis by influencing the tricarboxylic acid (TCA) cycle. Thus, CaGA nanozymes may be employed in the management of ulcerative colitis to control the intestinal milieu and improve the preservation of the intestinal barrier by decreasing the invasion of inflammatory cells and restoring mitochondrial activity. STATEMENT OF SIGNIFICANCE: CaGA nanozymes exhibit multifunctional enzymatic activity, effectively eliminating cellular RONS with robust antioxidant capacity. CaGA nanoenzymes promote macrophage M1 to M2 polarization and produce anti-inflammatory effects. CaGA nanozymes increase cell viability by restoring impaired mitochondrial function, reducing reactive oxygen species (ROS) production, and restoring the ability of mitochondria to produce ATP. CaGA nanozymes modulate intestinal flora diversity and composition, potentially influencing inflammatory pathways via aromatic compound metabolism. They participate in cellular energy and biosynthesis, regulating ulcerative colitis (UC)-related intestinal function through the tricarboxylic acid (TCA) and urea cycles. Calcium ions bind to GA nanomedicine and small particles are readily absorbed by inflammatory cells, preventing diarrhea from being rapidly excreted.

The microbiota composition is known to influence the kinetics of graft rejection, but many questions remain as to whether/how microbiota-derived metabolites affect graft outcome. We investigated the effects of the short-chain fatty acid butyrate, a product of dietary fiber fermentation. Sustained intragastric administration of a micelle-based formulation of butyrate (butyrate micelle [ButM]) that releases its cargo in the lower gastrointestinal tract elevated cecal butyrate content and significantly prolonged minor-mismatched and major-mismatched skin allograft survival in mice. While ButM did not influence regulatory T cells or the adaptive alloimmune responses we tested, it modulated the myeloid cell compartment. At steady state, ButM treatment reduced the number of circulating Ly6ChiCD11b+ monocytes and other myeloid cells in secondary lymphoid organs and skin, altered their expression of genes involved in mitochondrial metabolism and key inflammatory processes, and reduced their ability to produce TNFa, likely via an indirect mechanism. ButM treatment also reduced numbers of graft-infiltrating monocytes but not T cells. Consistent with its critical effect on myeloid cells, ButM's extension of graft survival depended on the presence of CCR2+ cells. These findings imply that cecal ButM improves distal allograft outcomes by quantitatively and qualitatively modulating myeloid cells, thereby inhibiting the innate immune cell-mediated effector phase of alloimmunity.

Polysaccharides, as complex carbohydrates, play a pivotal role in immune modulation and interactions with the gut microbiota. The diverse array of dietary polysaccharides influences gut microbial ecology, impacting immune responses, metabolism, and overall well-being. Despite their recognized benefits, there is limited understanding of the precise mechanisms by which polysaccharides modulate the immune system through the gut microbiota. A comprehensive search of Web of Science, PubMed, Google Scholar, and Embase up to May 2024 was conducted to identify relevant studies. This study employs a systematic approach to explore the interplay between polysaccharides and the gut microbiota, focusing on cytokine-mediated and short-chain fatty acid (SCFA)-mediated pathways. The findings underscore the significant role of polysaccharides in shaping the composition and function of the gut microbiota, thereby influencing immune regulation and metabolic processes. However, further research is necessary to elucidate the detailed molecular mechanisms and translate these findings into clinical applications.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that seriously affects the life expectancy of patients. Although increasingly sophisticated combinations of drugs can alleviate symptoms, 10-20% of patients still do not respond well. Therefore, it is necessary to further explore the pathogenesis and potential biomarkers of UC. Many clues have suggested the important value of mitochondrial metabolism in UC, but its role and related targets need to be further explored. By public database data, we identified differentially expressed mitochondrial metabolism related genes (MMRG) in UC. Subsequently, we identified biomarkers associated with MMRG based on a machine learning approach. After classifying the MMRG-associated molecular subtypes of UC, we comprehensively analyzed the MMRG biomarkers and the relationship between the MMRG molecular subtypes and immune infiltration characteristics. Single-cell sequencing analysis showed significant expression pattern of MMRG signatures in different cell subtypes. qRT-PCR and western blot further confirmed the abnormal expressions of selected genes in vitro. Our findings provided a new perspective on the role of MMRG in UC.

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders primarily comprising two main conditions: ulcerative colitis and Crohn's disease. The gut microbiota's role in driving inflammation in IBD has garnered significant attention, yet the precise mechanisms through which the microbiota influences IBD pathogenesis remain largely unclear. Given the limited therapeutic options for IBD, alternative microbiota-targeted therapies-including prebiotics, probiotics, postbiotics, and symbiotics-have been proposed. While these approaches have shown promising results, microbiota modulation is still mainly considered an adjunct therapy to conventional treatments, with a demonstrated impact on patients' quality of life. Fecal microbiota transplantation (FMT), already approved for treating Clostridioides difficile infection, represents the first in a series of innovative microbiota-based therapies under investigation. Microbial biotherapeutics are emerging as personalized and cutting-edge tools for IBD management, encompassing next-generation probiotics, bacterial consortia, bacteriophages, engineered probiotics, direct metabolic pathway modulation, and nanotherapeutics. This review explores microbial modulation as a therapeutic strategy for IBDs, highlighting current approaches and examining promising tools under development to better understand their potential clinical applications in managing intestinal inflammatory disorders.

The human microbiome, an intricate ecosystem of trillions of microbes residing across various body sites, significantly influences cancer, a leading cause of morbidity and mortality worldwide. Recent studies have illuminated the microbiome's pivotal role in cancer development, either through direct cellular interactions or by secreting bioactive compounds such as metabolites. Microbial metabolites contribute to cancer initiation through mechanisms such as DNA damage, epithelial barrier dysfunction, and chronic inflammation. Furthermore, microbial metabolites exert dual roles on cancer progression and response to therapy by modulating cellular metabolism, gene expression, and signaling pathways. Understanding these complex interactions is vital for devising new therapeutic strategies. This review highlights microbial metabolites as promising targets for cancer prevention and treatment, emphasizing their impact on therapy responses and underscoring the need for further research into their roles in metastasis and therapy resistance.

Acute respiratory distress syndrome (ARDS) is an often fatal critical illness where lung epithelial injury leads to intrapulmonary fluid accumulation. ARDS became widespread during the COVID-19 pandemic, motivating a renewed effort to understand the complex etiology of this disease. Rigorous prior work has implicated lung endothelial and epithelial injury in response to an insult such as bacterial infection; however, the impact of microorganisms found in other organs on ARDS remains unclear. Here, we use a combination of gnotobiotic mice, cell culture experiments, and re-analyses of a large metabolomics dataset from ARDS patients to reveal that gut bacteria impact lung cellular respiration by releasing metabolites that alter mitochondrial activity in lung epithelium. Colonization of germ-free mice with a complex gut microbiota stimulated lung mitochondrial gene expression. A single human gut bacterial species, Bifidobacterium adolescentis, was sufficient to replicate this effect, leading to a significant increase in mitochondrial membrane potential in lung epithelial cells. We then used genome sequencing and mass spectrometry to confirm that B. adolescentis produces L -lactate, which was sufficient to increase mitochondrial activity in lung epithelial cells. Finally, we found that serum lactate was significantly associated with disease severity in patients with ARDS from the Early Assessment of Renal and Lung Injury (EARLI) cohort. Together, these results emphasize the importance of more broadly characterizing the microbial etiology of ARDS and other lung diseases given the ability of gut bacterial metabolites to remotely control lung cellular respiration. Our discovery of a single bacteria-metabolite pair provides a proof-of-concept for systematically testing other microbial metabolites and a mechanistic biomarker that could be pursued in future clinical studies. Furthermore, our work adds to the growing literature linking the microbiome to mitochondrial function, raising intriguing questions as to the bidirectional communication between our endo- and ecto-symbionts.

Methionine restriction has received some attention in recent years as a novel mode of dietary intervention. Our previous study found that methionine restriction could inhibit the celiac toxic effects of wheat gluten in an in vitro model. However, the role of methionine restriction in gluten-induced celiac intestinal damage remains unclear. The aim of this study was to explore whether dietary methionine restriction could suppress the celiac toxic effects of gluten in an in vivo model, thereby mitigating intestine damage. This study systematically investigated the effects of dietary methionine restriction on celiac characteristic indicators such as symptoms, small intestine damage, and intestinal TG2 and IL-15 expression in a gluten-induced C57BL/6 mouse model. The availability of dietary methionine restriction in different ages (adolescent and adult) was also evaluated. Moreover, mouse cecum contents were assayed and co-analyzed for the metagenome of intestinal flora and target short-chain fatty acid metabolomics, with the goal of further exploring and elucidating critical pathways by which dietary methionine restriction plays a role. We discovered that dietary methionine restriction could effectively ameliorate the gluten-induced celiac-associated small intestine damage by modulating intestinal flora to inhibit butyric acid production. Specifically, dietary methionine restriction could inhibit butyric acid production with the help of s_CAG-485 sp002493045 and s_CAG-475 sp910577815, which in turn affected the mitochondrial function within the intestinal epithelial cells to assist in the repair of intestine damage. This study might provide new insights into modulating dietary patterns to mitigate intestinal damage in celiac disease and the production of novel gluten-free products.

The current experiment aimed to investigate the effects of sodium butyrate (SB) and vitamin D3 (VD3) supplementation on the growth performance, immune status, antioxidant capacity, and gut health of young broilers under cold stress. A total of 144 1-day-old Arbor Acres chicks were randomly allotted to three treatments with 6 replicates of 8 birds: (1) basal diet; (2) basal diet + cold stress; and (3) basal diet with 1 g/kg SB and 2000 IU/kg VD3 + cold stress. Birds were exposed to cold stress at 16 ± 1 °C for 72 h (d 18-21) and 26 ± 1 °C for the control. The results indicated that the SB/VD3 diet could alleviate the reduction in average daily gain (ADG) caused by cold stress (p < 0.05). The SB/VD3 diet decreased the serum endotoxin level and ileal interleukin-1β gene expression and upregulated interleukin-10 and nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression compared with cold-stressed birds (p < 0.05). Furthermore, cold stress altered the composition of gut microbiota, including a decrease in Clostridium_sensu_stricto_1, whereas the SB/VD3 diet prevented the reduction. In conclusion, the SB/VD3 diet mitigated the negative effects of cold stress on growth performance and the intestines by strengthening intestinal barrier function and stabilizing gut microbiota balance in broiler chicks, and these results can help to manage cold stress.

Microbiome science has greatly expanded our understanding of the diverse composition and function of gut microorganisms over the past decades. With its rich microbial composition, the microbiome hosts numerous functionalities essential for metabolizing food ingredients and nutrients, resulting in the production of active metabolites that affect food fermentation or gut health. Most of these processes are mediated by microbial enzymes such as carbohydrate-active enzymes and amino acid metabolism enzymes. Metatranscriptomics enables the capture of active transcripts within the microbiome, providing invaluable functional insights into metabolic activities. Given the inter-kingdom complexity of the microbiome, metatranscriptomics could further elucidate the activities of fungi, archaea, and bacteriophages in the microbial ecosystem. Despite its potential, the application of metatranscriptomics in food and nutrition sciences remains limited but is growing. This review highlights the latest advances in food science (e.g., flavour formation and food enzymology) and nutrition science (e.g., dietary fibres, proteins, minerals, and probiotics), emphasizing the integration of metatranscriptomics with other technologies to address key research questions. Ultimately, metatranscriptomics represents a powerful tool for uncovering the microbiome activity, particularly in relation to active metabolic processes.

Chronic visceral hypersensitivity is associated with an overstressed pain response to noxious stimuli (hyperalgesia). Microbiota are active modulators of host biology and are implicated in the etiology of visceral hypersensitivity.

we studied the association between the circulating mRNA transcriptome, the intensity of induced visceral pain (IVP), and variation in the oral microbiome among participants with and without baseline visceral hypersensitivity.

Transcriptomic profiles and microbial abundance were correlated with IVP intensity. Host mRNA and microbes associated with IVP were explored, linking variation in the microbiome to host RNA biology.

259 OTUs were found to be associated with IVP through correlation to differential expression of 471 genes in molecular pathways related to inflammation and neural mechanisms, including Rho and PI3K/AKT pathways. The bacterial families Lachnospiraceae, Prevotellaceae, and Veillonellaceae showed the highest degree of association. Oral microbial profiles with reduced diversity were characteristic of participants with visceral hypersensitivity.

Our results suggest that the oral microbiome may be involved in systemic immune and inflammatory effects and play a role in nervous system and stem cell pathways. The interactions between visceral hypersensitivity, differentially expressed molecular pathways, and microbiota described here provide a framework for further work exploring the relationship between host and microbiome.

Understanding the role of the gut microbiota in the pathogenesis of inflammatory bowel diseases (IBD) has been an area of intense research over the past decades. Patients with IBD exhibit alterations in their microbial composition compared to healthy controls. However, studies focusing solely on taxonomic analyses have struggled to deliver replicable findings across cohorts regarding which microbial species drive the distinct patterns in IBD. The focus of research has therefore shifted to studying the functionality of gut microbes, especially by investigating their effector molecules involved in the immunomodulatory functions of the microbiota, namely metabolites. Metabolic profiles are altered in IBD, and several metabolites have been shown to play a causative role in shaping immune functions in animal models. Therefore, understanding the complex communication between the microbiota, metabolites, and the host bears great potential to unlock new biomarkers for diagnosis, disease course and therapy response as well as novel therapeutic options in the treatment of IBD. In this review, we primarily focus on promising classes of metabolites which are thought to exert beneficial effects and are generally decreased in IBD. Though results from human trials are promising, they have not so far provided a large-scale break-through in IBD-therapy improvement. We therefore propose tailored personalized supplementation of microbiota and metabolites based on multi-omics analysis which accounts for the individual microbial and metabolic profiles in IBD patients rather than one-size-fits-all approaches.

The production of short-chain fatty acids (SCFAs) by Firmicutes (Bacillota) within the human gastrointestinal tract is recognized as critical for gut health and the progression of a range of disease states. Firmicutes are the most diverse phylum of human gut bacteria, are highly studied, and are often specialized to degrade just a few polysaccharide substrates. Members of the Firmicutes include key bacteria that produce butyrate, an SCFA that is generally not produced by members of the other major phyla. Recently, it was shown that Eubacterium rectale, a widespread member of the Firmicutes belonging to the Clostridiales cluster XIVa, can grow on the unusual but ubiquitous plant-derived sugar SQ using a sulfoglycolytic sulfofructose transaldolase pathway. Here, we show that in addition to SQ, E. rectale can also grow on the SQ glycoside sulfoquinovosyl glycerol (SQGro). The 3D structure of the E. rectale sulfoquinovosidase (SftG) shares strong structural conservation with other carbohydrate-active enzyme family GH31 SQases. Using sequence-similarity networks, we provide new biological context to a conserved domain of unknown function protein SftX belonging to DUF4867, which is conserved in the sulfoglycolytic sulfofructose transaldolase pathway, and determine its 3D structure. Finally, with the aid of a synthetic mini-human microbiome reconstituted in germ-free mice, we show that an SQ dietary supplement can rescue E. rectale from population crashes that occur upon switching from a high-fiber to a low-fiber, high-fat diet. This suggests that SQ or SQGro has the potential as a prebiotic for promoting the maintenance of this important butyrate-producing bacterium within the colonic microbiota.

Recently, the non-intestinal functions of human milk oligosaccharides (HMOs) have been widely documented, including their roles in promoting brain development and growth, as well as ameliorating anxiety, allergies, and obesity. Understanding their mechanisms of action is becoming increasingly critical. Furthermore, these effects are frequently associated with the type and structure of HMOs. As an innovative technology, "plant factory" is expected to complement traditional synthesis technology. This study reviews the novel "plant factory" synthesis techniques. Particular emphasis is placed on the processes, advantages, and limitations of "plant factory" synthesis of HMOs. This technology can express genes related to HMO synthesis instantaneously in plant leaves, thereby enabling the rapid and cost-effective generation of HMOs. However, "plant factory" technology remains underdeveloped, and challenges related to low yield and unsustainable production must be addressed. Furthermore, we present an overview of the most recent clinical and preclinical studies on the non-intestinal functions of HMOs. This review emphasizes the mechanisms of action underlying the non-intestinal functions of HMOs. HMOs primarily exert non-intestinal functions through the cleavage of beneficial monomer components, metabolism to produce advantageous metabolites, and regulation of immune responses.

The unfolded protein response (UPR) is a complex intracellular signal transduction system that orchestrates the cellular response during Endoplasmic Reticulum (ER) stress conditions to reestablish cellular proteostasis. If, on one side, prolonged ER stress conditions can lead to programmed cell death and autophagy as a cytoprotective mechanism, on the other, unresolved ER stress and improper UPR activation represent a perilous condition able to trigger or exacerbate inflammatory responses. Notably, intestinal and immune cells experience ER stress physiologically due to their high protein secretory rate. Indeed, there is evidence of UPR's involvement in both physiological and pathological intestinal conditions, while less is known about its bidirectional interaction with gut microbiota. However, gut microbes and their metabolites can influence ER stress and UPR pathways, and, in turn, ER stress conditions can shape gut microbiota composition, with important implications for overall intestinal health. Thus, targeting UPR components is an intriguing strategy for treating ER stress-linked dysbiosis and diseases, particularly intestinal inflammation.