Lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, triggers inflammatory responses in intestinal epithelial cells. This activation leads to the production of pro-inflammatory cytokines which disrupt cellular homeostasis. LPS also impairs the integrity of the intestinal epithelial barrier by downregulating tight junction proteins, resulting in increased intestinal permeability. This compromised barrier function can allow further translocation of luminal antigens, perpetuating inflammation and contributing to gut-related disorders such as inflammatory bowel disease (IBD) and metabolic endotoxemia. This study investigated the therapeutic effects of inulin, a prebiotic dietary fiber, in attenuating LPS-induced intestinal epithelial barrier dysfunction. Caco-2 cells were treated with 100 ng/mL of LPS for 12 h, resulting in increased gene expression of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-18) and a significant downregulation of tight junction proteins claudin-1 and claudin-2, while occludin gene expression remained unaffected. Pretreatment with 2% inulin for 24 h before LPS exposure prevented the downregulation of claudin-1 and claudin-2 and significantly upregulated occludin gene expression. These molecular findings were supported by functional assays using transwell systems. LPS treatment increased paracellular permeability of the Caco-2 monolayer, indicating barrier dysfunction, while inulin pretreatment mitigated this effect. These results demonstrate that inulin can modulate tight junction protein expression and maintain gut barrier integrity under inflammatory conditions.

Butyrate may decrease intestinal inflammation and diarrhea. This study investigates the impact of oral application of sodium butyrate (NaB) and tributyrin (TB) on colonic butyrate concentration, SCFA transporter expression, colonic absorptive function, barrier properties, inflammation, and microbial composition in the colon of slc26a3-/- mice, a mouse model for inflammatory diarrhea. In vivo fluid absorption and bicarbonate secretory rates were evaluated in the cecum and mid-colon of slc26a3+/+ and slc26a3-/- mice before and during luminal perfusion of NaB-containing saline and were significantly stimulated in both slc26a3+/+ and slc26a3-/- colon by NaB. Age-matched slc26a3+/+ and slc26a3-/- mice were either fed chow containing 5% NaB or gavaged twice daily with TB for 21 d. Food and water intake, weight, and stool water content were assessed daily. Stool and tissues were collected for further analysis of SCFA production, barrier integrity, mucosal inflammation, and microbiome analysis by 16S rRNA gene sequencing. 5% NaB diet did not exert a significant impact on SCFA levels, mucus barrier, or inflammatory markers, but significantly increased oral water intake. TB gavage treatment increased the expression of SCFA transporters Mct1 and Smct1, mucus content and microbial diversity, and decreased the neutrophil marker Lipocalin 2, Phospholipase A2, and the antimicrobial peptide Reg3b in the slc26a3-/- cecum. However, TB treatment also resulted in an increase in inflammatory markers such as TNFα, Il-1β and CD3e in the wildtype mucosa. While there are some benefits with TB ingestion for barrier properties and microbial composition in the diseased cecum, potentially detrimental effects were noted in the healthy colon.

Diabetic stroke-associated acute intestinal injury is characterized by high mortality, disability, and poor prognosis due to the lack of effective therapies. Our prior research demonstrated that administration of 300 mg/kg sodium butyrate (NaB) can improve neurological outcomes post-diabetic stroke. Nonetheless, whether the effect of NaB is related to intestinal regulation, along with its underlying mechanisms, remains uncertain. This study aims to investigate the effects and mechanistic pathways of NaB on diabetic stroke-associated acute intestinal injury. A middle cerebral artery occlusion/reperfusion model was established in mice with streptozotocin-induced diabetes. The results demonstrated that NaB alleviated colonic injury 24 h after reperfusion in diabetic stroke. Pyroptosis-related protein levels in colonic tissues were significantly elevated following diabetic stroke but were markedly reduced with NaB treatment. NaB also improved gut barrier integrity and reduced inflammation, promoting epithelial barrier self-repair. In the NaB combined with lipopolysaccharide group, lipopolysaccharide administration induced a significant inflammatory response in the colonic tissue. Conversely, treatment with NaB and VX-765 (an inhibitor for Caspase-1) led to a notable alleviation in intestinal inflammation. These findings suggest that NaB mitigates colonic injury and enhances barrier function following diabetic stroke, potentially through the Caspase-1/Gasdermin D pyroptosis pathway. This study may provide a novel strategy and direction for intestinal rehabilitation in diabetic stroke patients.

Immune-related adverse events (irAEs) pose a significant challenge to the clinical use of immune checkpoint inhibitors (ICIs) in cancer immunotherapy. This study aims to determine whether comorbid conditions such as type 2 diabetes (T2DM), hypertension, and hyperlipidemia affect the risk of irAEs in cancer patients receiving ICIs treatments.

We conducted a retrospective analysis of clinical data from 3,489 cancer patients treated with ICIs (anti-PD-1, anti-PD-L1, and anti-CTLA-4) at West China Hospital of Sichuan University from 2017 to 2022. Logistic regression models were used to evaluate the associations between T2DM, hypertension, and hyperlipidemia with irAEs. Subgroup analyses assessed irAEs in patients with and without these comorbidities across different cancer types. Additionally, we explored the associations between comorbidities and irAEs affecting different organs.

The results showed that comorbid T2DM, hypertension, and hyperlipidemia significantly increased the risk of irAEs in all cancer types (T2DM: OR=1.40, 95% CI: 1.12-1.74, p=0.003; hypertension: OR=1.21, 95% CI: 1.00-1.45, p=0.049; hyperlipidemia: OR=1.62, 95% CI: 1.02-2.53, p=0.038). T2DM primarily increased the risk of irAEs in lung cancer patients (OR = 1.50, 95% CI: 1.12-2.01, FDR-adjusted p = 0.036), and all three comorbidities significantly elevated the risk of cardiac irAEs.

Our study is the first to confirm an association between T2DM, hypertension, and hyperlipidemia and the occurrence of irAEs in cancer patients receiving ICIs therapy. This finding highlights the critical need for clinicians to perform comprehensive evaluations of patients' comorbidities prior to treatment.

Dietary modification is a cornerstone and a primary goal for weight loss, whose effects may be related to epigenetic phenomena. In this literature review, a comprehensive search without time restriction was performed in PubMed/Medline, Cochrane, SciELO, and Scopus databases to identify epigenetic signatures related to obesity outcomes upon dietary advice. In this context, experimental studies and clinical trials have identified certain DNA methylation marks, miRNA expression profiles and histone modifications putatively associated with adiposity outcomes after different nutritional interventions. These include traditional dietary patterns, diets with different macronutrient compositions, and supplementation with fatty acids, amino acids and derivatives, methyl donors, vitamins and minerals, probiotics and prebiotics, and bioactive food compounds. Some of these epigenetic signatures have been mapped to genes involved in food intake control, adipogenesis, lipolysis, fatty acid oxidation, body fat deposition, and gut microbiota modulation. However, additional studies are still required to address dosage and follow-up variability, validation of epigenetic marks, genome-wide approaches, and appropriate statistical settings. Although more investigation is required, these insights may contribute to the characterization of epigenetic biomarkers of body weight regulation toward the prescription of tailored dietary strategies targeting the epigenome for a more precise obesity management and control.

BDE-209 has a causal relationship with adverse health outcomes. However, research on its effect on bone homeostasis is relatively lacking. This study examined the relationship between BDE-209 exposure and bone health, as well as the underlying mechanisms, using both in vitro and in vivo models. In animal studies, female SD rats were administered BDE-209 for 60 days. Bone mineral density, bone microstructure, gut microbiota, and inflammaging markers were measured. Furtherly, THP-1 cell-derived macrophages were treated with a culture medium containing population-relevant dose of BDE-209 or sodium butyrate. The expression of M1 macrophage markers, osteoclast markers, and inflammatory cytokines was measured. Then macrophages were induced by osteoclast conditioned medium to evaluate the effect of BDE-209 on their differentiation into osteoclasts. Results showed reduced humeral bone density, enhanced osteoclast activity, upregulation of IL-1β, TNF-α, IL-6, and activation of PGC-1α/NAD+/cGAS-STING in the exposed group. 16s sequencing revealed that BDE-209 disrupts the abundance of the gut microbiota, notably a reduction in Lachnospiraceae. In vitro, BDE-209 can stimulate macrophages to differentiate more osteoclasts and activate the cGAS-STING pathway, while sodium butyrate can inhibit these effects. This study reveals that gut microbiota dysbiosis is involved in BDE-209-induced bone homeostasis disorder through inflammatory aging and sodium butyrate can mitigate this effect. Overall, this study provides research data for the precaution and treatment of osteoporosis associated with BDE-209 exposure.

The gut microbiota plays a crucial role in the communication between the gut, liver, and brain through the production of short chain fatty acids (SCFAs). SCFAs serve as key mediators in the Gut-Liver-Brain Axis, influencing various physiological processes and contributing to overall health. SCFAs are produced by bacterial fermentation of dietary fiber in the gut, and they exert systemic effects by signaling through various pathways. In the Gut-Liver axis, SCFAs regulate liver metabolism through peroxisome proliferator-activated receptor-γ (PPAR-γ), AMP-activated protein kinase (AMPK) and other pathways, promotes fat oxidation, modulate inflammation through mTOR pathway, and impact metabolic health. In the Gut-Brain axis, SCFAs influence brain function, behavior, and may have implications for neurological disorders, in which G-protein coupled receptors (GPCRs) play an essential role, along with other pathways such as hypothalamic-pituitary-adrenal (HPA) pathway. Understanding the mechanisms by which SCFAs mediate communication between the gut, liver, and brain is crucial for elucidating the complex interplay of the Gut-Liver-Brain Axis. This review aims to provide insight into the role of gut microbiota-derived SCFAs as mediators of the Gut-Liver-Brain Axis and their potential therapeutic implications. Further research in this area will be instrumental in developing novel strategies to target the Gut-Liver-Brain Axis for the prevention and treatment of various health conditions.

The gastrointestinal (GI) tract is susceptible to damage under high altitude hypoxic conditions, leading to gastrointestinal discomfort and intestinal barrier injury. Sodium butyrate, a short-chain fatty acid present as a metabolite in the gut, has emerged as a promising therapeutic agent due to its ability to act as an immunomodulatory agent and restore intestinal barrier integrity. This study aimed to explore the mechanism by which sodium butyrate exhibits anti inflammatory effect on intestinal epithelial cells. In vitro, Caco-2 epithelial cells and RAW 264.7 macrophages were used to investigate the protective role of sodium butyrate on Lipopolysaccharide (LPS) induced inflammation. Cell viability assays demonstrated that 1 mM (110.86 μg/mL) of sodium butyrate did not exhibit cytotoxicity on cells in vitro. Treatment with sodium butyrate suppressed reactive oxygen species levels and TNF-α production in LPS-stimulated macrophages, indicating its efficacy in mitigating inflammatory responses. Western blot analysis revealed that sodium butyrate attenuated the expression of iNOS in RAW 264.7 macrophage cells. Moreover, sodium butyrate also reversed the LPS induced over expression of HIF-1α, NLRP3, IL-1β as well as NF-kB in Caco-2 epithelial cells and also had a suppressive effect on IL-8 secretion after LPS stimulation. Immunocytochemistry demonstrated that sodium butyrate enhanced tight junction protein occludin expression in Caco-2 cells while also restoring the decreased permeability of the Caco-2 monolayer due to LPS. These results indicate that sodium butyrate may influence immune responses by suppressing inflammatory mediators and improving the integrity of the epithelial barrier. Understanding the intricate interactions between gut metabolites and host immune responses may help in the development of innovative therapeutic strategies to alleviate intestinal inflammation in high altitude environments.

The contemporary approach to nutrition increasingly considers the role of non-nutritive bioactive compounds in modulating the immune system and maintaining health. This article provides up-to-date insight into the immunomodulatory effects of selected bioactive compounds, including micro- and macronutrients, vitamins, as well as other health-promoting substances, such as omega-3 fatty acids, probiotics, prebiotics, postbiotics (including butyric acid and sodium butyrate), coenzyme Q10, lipoic acid, and plant-derived components such as phenolic acids, flavonoids, coumarins, alkaloids, polyacetylenes, saponins, carotenoids, and terpenoids. Micro- and macronutrients, such as zinc, selenium, magnesium, and iron, play a pivotal role in regulating the immune response and protecting against oxidative stress. Vitamins, especially vitamins C, D, E, and B, are vital for the optimal functioning of the immune system as they facilitate the production of cytokines, the differentiation of immunological cells, and the neutralization of free radicals, among other functions. Omega-3 fatty acids exhibit strong anti-inflammatory effects and enhance immune cell function. Probiotics, prebiotics, and postbiotics modulate the intestinal microbiota, thereby promoting the integrity of the intestinal barrier and communication between the microbiota and the immune system. Coenzyme Q10, renowned for its antioxidant attributes, participates in the protection of cells from oxidative stress and promotes energy processes essential for immune function. Sodium butyrate and lipoic acid exhibit anti-inflammatory effects and facilitate the regeneration of the intestinal epithelium, which is crucial for the maintenance of immune homeostasis. This article emphasizes the necessity of an integrative approach to optimal nutrition that considers not only nutritional but also non-nutritional bioactive compounds to provide adequate support for immune function. Without them, the immune system will never function properly, because it has been adapted to this in the course of evolution. The data presented in this article may serve as a foundation for further research into the potential applications of bioactive components in the prevention and treatment of diseases associated with immune dysfunction.

Animals infected with mycoplasma pneumoniae not only develop respiratory diseases, but also cause digestive diseases through the lung-gut axis mediated by the intestinal flora, and vice versa. Antimicrobial peptides are characterized by their bactericidal, anti-inflammatory, and intestinal flora-regulating properties. However, the effect of cecropin AD (CAD) against mycoplasma pneumonia remains unclear. To investigate the anti-inflammatory effect of CAD on mycoplasma pneumonia and the associated mechanism, mice were infected with Mycoplasma capricolum subsp. Capripneumoniae(Mccp) to elicit lung inflammation, followed by oral administration of CAD via gavage. The findings showed that mice receiving twice injections of 2.08 × 108 copies of Mccp suffered significant pathological damage to their lungs and colons. Additionally, there was a notable upsurge in inflammatory factors within the affected tissues. 16 S rDNA sequencing revealed alterations in the colonic microbiota, including a decrease in the abundance of beneficial bacteria such as Corynebacterium_glutamicum and Candidatus_Saccharimonas, and an increase in the abundance of potential pathogens like Lachnospiraceae_NK4A136_group and Escherichia-Shigella. As a result, there were abnormal rises in lipopolysaccharide (LPS) levels in both colonic content and blood. Moreover, CAD treatment reversed the microbial dysbiosis and decreased the LPS levels induced by Mccp, thereby suppressing the activation of the TLR-4/NF-κB pathway and the Fas/FasL-caspase-8/-3 pathway. Consequently, this significantly mitigated the morphological and functional damage to the lungs and colons caused by Mccp. The findings offer novel insights and approaches for the clinical management of Mccp infections.

The relationship between the gut microbiome and metabolic dysfunction-associated fatty liver disease (MAFLD) has garnered increasing attention. However, the association between the dietary index for gut microbiota (DI-GM), a measure of microbiome diversity, and MAFLD has yet to be fully explored.

Data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) were analyzed, including 7243 participants. The association between DI-GM and MAFLD was investigated using weighted logistic regression, restricted cubic spline (RCS), and subgroup analyses.

A notable inverse association was identified between DI-GM and the prevalence of MAFLD, with each 1-point increase in DI-GM corresponding to a 6.1% reduction in MAFLD prevalence (OR = 0.939, 95% CI: 0.901-0.980). Individuals with a DI-GM score of 6 or higher had an adjusted OR of 0.794 (95% CI: 0.665-0.947) compared to those with a DI-GM score of 0-3. RCS analysis further revealed a linear relationship between DI-GM and MAFLD risk. Additionally, subgroup analyses suggested that race may modify the association between DI-GM and MAFLD (P for interaction < 0.05).

DI-GM is inversely associated with MAFLD prevalence, and race appears to be a significant modifier of this relationship.

The incidence of NAFLD is increasing. Preclinical evidences indicate that modulation of the gut microbiome could be a promising target in nonalcoholic fatty liver disease.

A systematic review and network meta-analysis was conducted to compare the effect of probiotics, synbiotics, prebiotics, fecal microbiota transplant, and antibiotics on the liver-enzyme, metabolic effects and liver-specific in patients with NAFLD. The randomized controlled trails (RCTs), limited to English language were searched from database such as Pubmed, Embase, Web of science and Cochrane Library from inception to November 2024. Review Manager 5.3 was used to to draw a Cochrane bias risk. Inconsistency test and publication-bias were assessed by Stata 14.0. Random effect model was used to assemble direct and indirect evidences. The effects of the intervention were presented as mean differences with 95% confidence interval.

A total of 1921 patients from 37 RCTs were eventually included in our study. 23 RCTs evaluated probiotics, 10 RCTs evaluated synbiotics, 4 RCTs evaluated prebiotics, 3 RCTs evaluated FMT and one RCT evaluated antibiotics. Probiotics and synbiotics were associated with a significantly reduction in alanine aminotransferase [ALT, (MD: -5.09; 95%CI: -9.79, -0.39), (MD: -7.38, 95CI%: -11.94, -2.82)] and liver stiffness measurement by elastograph [LSM, (MD: -0.37;95%CI: -0.49, -0.25), (MD: -1.00;95%CI: -1.59, -0.41)]. In addition to, synbiotics was superior to probiotics in reducing LSM. Synbiotics was associated with a significant reduction of Controlled Attenuation Parameter [CAP, (MD: -39.34; 95%CI: -74.73, -3.95)]. Both probiotics and synbiotics were associated with a significant reduction of aspartate transaminase [AST, (MD: -7.81; 95%CI: -15.49, -0.12), (MD: -13.32; 95%CI: -23, -3.64)]. Probiotics and Allogenic FMT was associated with a significant reduction of Homeostatic Model Assessment for Insulin Resistance [HOMA-IR, (MD: -0.7, 95%CI: -1.26, -0.15), (MD: -1.8, 95%CI: -3.53, - 0.07)]. Probiotics was associated with a significant reduction of body mass index [BMI, MD: -1.84, 95%CI: -3.35, -0.33].

The supplement of synbiotics and probiotics maybe a promising way to improve liver-enzyme, LSM, and steatosis in patients with NAFLD. More randomized controlled trials are needed to determine the efficacy of FMT and antibiotics on NAFLD. And the incidence of adverse events of MTTs should be further explored.

https://www.crd.york.ac.uk/prospero/, CRD42023450093.

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.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease closely related to gut microbiota dysbiosis and intestinal homeostasis imbalance. Sishen Pill&Tongxieyaofang (SSP-TXYF) has a long history of application in traditional Chinese medicine and is widely used in UC clinics. However, its mechanism of action is still unclear.

This study aimed to explore the potential regulatory role of SSP-TXYF in protecting against UC through metabolites produced by the intestinal microbiota, and elucidate its underlying molecular mechanism.

16S rRNA and UPLC-QE-Orbitrap-MS were used to assess the microbiota and short-chain fatty acids (SCFAs). A rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced gut microbiota dysbiosis was used to study the effects of SSP-TXYF on UC in vivo. Intestinal epithelial cells-6 (IEC-6) were treated with lipopolysaccharide (LPS). The intestinal mucosal barrier (IMB) functions were investigated by alcian blue staining and western blot analysis. The mechanism of SSP-TXYF influenced the HIF-1α acetylation pathway was examined by real-time fluorescence quantitative PCR (qPCR), Western blotting, and Co-immunoprecipitation.

Using 16S rRNA gene-based microbiota analysis, we found that SSP-TXYF ameliorated TNBS-induced gut microbiota dysbiosis. We found that SSP-TXYF significantly inhibited the decreased abundance of Firmicutes in UC rats, in addition, the abundance of Actinobacteria was also improved. The mechanism of SSP-TXYF-treated TNBS-induced UC resulted from improved IMB functions via the activation of hypoxia-inducible factor-1 (HIF-1α) acetylation. Notably, SSP-TXYF Enriched microbiota-derived metabolites propionate and butyrate, which could activate HIF-1α acetylation in IEC. Furthermore, exogenous treatment of propionate and butyrate reproduced similar protective effects as SSP-TXYF to UC through improving HIF-1α-dependent IMB functions.

Overall, our findings suggest that the gut microbiota-propionate/butyrate-HIF-1α-IMB axis plays an important role in SSP-TXYF-maintaining intestinal homeostasis, which may represent a novel approach for UC prevention via the intervention of any link in this axis.

Endotoxemia is closely related to many diseases. As the largest endotoxin reservoir in the human body, the gut microbiota should be a key target for alleviating endotoxemia. The intestinal microbiota is believed to cause endotoxemia directly or indirectly by modifying the intestinal barrier function through dysbiosis, changing intestinal mucosal permeability and bacterial translocation. Diet is known to be the main environmental factor affecting the intestinal microbiota, and different diets and food components have a large impact on the gut microbiota. The Mediterranean diet, which received much attention in recent years, is believed to be able to regulate the gut microbiota, thereby maintaining the function of the intestinal barrier and alleviating endotoxemia. In this review, we focus on the relationship between the gut microbiota and endotoxemia, and how the Mediterranean dietary (MD) pattern can interfere with endotoxemia through the gut microbiota.

The global epidemic of type 2 diabetes mellitus (T2DM) imposes a substantial burden on public health and healthcare expenditures, thereby driving the pursuit of cost-effective preventive and therapeutic strategies. Emerging evidence suggests a potential association between dysbiosis of gut microbiota and its metabolites with T2DM, indicating that targeted interventions aimed at modulating gut microbiota may represent a promising therapeutic approach for the management of T2DM. In this review, we concentrated on the multifaceted interactions between the gut microbiota and the intestinal barrier in the context of T2DM. We systematically summarized that the imbalance of beneficial gut microbiota and its metabolites may constitute a viable therapeutic approach for the management of T2DM. Meanwhile, the mechanisms by which gut microbiota interventions, such as probiotics, prebiotics, postbiotics, and synbiotics, synergistically improve insulin resistance in T2DM are summarized. These mechanisms include the restoration of gut microbiota structure, upregulation of intestinal epithelial cell proliferation and differentiation, enhancement of tight junction protein expression, promotion of mucin secretion by goblet cells, and the immunosuppressive functions of regulatory T cells (Treg) and M2 macrophages. Collectively, these actions contribute to the amelioration of the body's metabolic inflammatory status. Our objective is to furnish evidence that supports the clinical application of probiotics, prebiotics, and postbiotics in the management of T2DM.

Type 2 diabetes (T2D), a global health concern, is closely associated with the gut microbiota. Restoration of a balanced microbiota and intestinal homeostasis benefit therapy of T2D. Some special phages may selectively alter the gut microbiota without causing dysbiosis, such as MS2 and P22. However, scarcely systematic analysis of cascading effects triggered by MS2 and P22 phages on the microbiota, as well as interactions between specific gut bacteria and systemic metabolism, seriously inhibit the development of positive interventions of phages. Based on multi-omic analysis, we analyzed the intrinsic correlations among specific microbiota, their bioactive metabolites, and key indicators of T2D. We found that gavage of the MS2-P22 phage cocktail could significantly alter the gut microbiome to attenuate dysbiosis of diabetic C57BL/6 mice caused by high-fat diets (HFDs) and streptozotocin (STZ), by affecting microbial compositions as well as their metabolic pathways and metabolites, especially increasing amounts of short-chain fatty acid-producing (SCFA-producing) bacteria (e.g., Blautia and Romboutsia) and short-chain fatty acids (SCFAs). Correspondingly, a noteworthy reduction in the number of several opportunistic pathogens occurred, e.g., Candidatus Saccharimonas, Aerococcus, Oscillibacter, Desulfovibrio, and Clostridium sensu stricto 1. Synchronously, the levels of proinflammatory cytokines and lipopolysaccharide (LPS) were reduced to recover gut barrier function in T2D mice. These findings might benefit the development of a new dietary intervention for T2D based on phage cocktails. KEY POINTS: • Intestinal barrier integrity of T2D mice is improved by a phage cocktail • Negative relationship between Muribaculaceae and Corynebacterium reshaped gut microbiota • Acetate, propionate, and butyrate decreased the level of proinflammatory factors.

Infection by pathogenic bacteria during weaning is a common cause of diarrhea and intestinal inflammation in piglets. Supplementing the diet with synbiotics is beneficial for animal health. The strain of Lactiplantibacillus plantarum L47 (L47) isolated in our lab exhibited good probiotic properties when combined with inulin. Here, the effectiveness of combining L47 and inulin (CLN) in protecting against enterotoxigenic Escherichia coli (ETEC) induced colon and liver inflammation in weaned piglets was evaluated.

Twenty-eight piglets aged 21 days were randomly assigned into 4 groups: CON (control), LI47 (oral CLN culture fluid, 1010 CFU/d of L47 and 1 g/d of inulin), ECON (oral ETEC culture fluid, 1010 CFU/d), and ELI47 (oral CLN and ETEC culture fluid). After 24 days, the colon and liver samples were collected for further analysis.

CLN alleviated colon damage caused by ETEC challenge, as evidenced by an increase of colonic crypt depth, mRNA expression of tight junction Claudin-1 and Occludin, GPX activity, the concentration of IL-10 and sIgA (p < 0.05). Moreover, there was a decrease in MDA activity, the load of E. coli, the concentration of LPS, gene expression of TLR4, and the concentration of TNF-α and IL-6 (p < 0.05) in colonic mucosa. Additionally, CLN counteracted liver damage caused by ETEC challenge by modulating pathways associated with immunity and disease occurrence (p < 0.05).

Supplementing with CLN alleviated colon inflammation induced by ETEC challenge by decreasing the E. coli/LPS/TLR4 pathway and regulating hepatic immune response and disease-related pathways, suggesting that CLN could protect intestinal and liver health in animals.

This study was conducted to explore the protective effects of inulin against lipopolysaccharide (LPS)-induced inflammatory response and intestinal barrier dysfunction in broilers. 108 broilers were allocated to 3 treatments: 1) non-challenged broilers (Control, CON); 2) LPS-challenged broilers (LPS); 3) LPS-challenged broilers fed the basal diet supplemented with 15 g/kg of inulin (Inulin + LPS). At 21 d of age, the LPS-challenged groups received an intraperitoneal injection of LPS, and the CON group received an equal volume of saline. After 4 h of LPS exposure, samples of blood, intestinal mucosa and cecal digesta were collected. The results showed that LPS challenge induced systemic inflammation and damaged intestinal barrier function, whereas inulin attenuated LPS-induced production of pro-inflammatory cytokines by inhibiting the activation of TLR4 and NF-κB p65, and enhanced intestinal barrier function. In addition, LPS stimulation caused cecal microbial dysbiosis as shown by increased abundance of pathogenic bacteria including Ruminococcus_torques_group, Escherichia-Shigella and Subdoligranulum, while supplementation of inulin increased abundance of beneficial bacteria Faecalibacterium and Anaeroplasma, and metabolite production including propionate and butyrate concentrations. In conclusion, dietary supplementation of inulin could partially alleviate LPS-induced inflammation and intestinal barrier injury by modulating intestinal microbiota, thereby minimizing growth retardation of broilers. Our results provide a basis for the rational utilization of inulin in alleviating immune stress in broiler production.

Heat stress adversely affects poultry production and meat quality, leading to economic losses. This study aimed to investigate the effects of adding tributyrin on growth performance, meat quality, muscle oxidative status, and gut microbiota of Taihe silky fowls under cyclic heat stress (CHS) conditions. In this study, 120-day-old Taihe silky fowls (male) were randomly divided into six dietary treatments. These treatments included a normal control treatment (NC, fed a basal diet), a heat stress control treatment (HS, fed a basal diet), and HS control treatments supplemented with 0.04%, 0.08%, 0.16%, and 0.32% tributyrin, respectively. The NC treatment group was kept at 24 ± 1 °C, while the HS treatment birds were exposed to 34 ± 1 °C for 8 h/d for 4 weeks. Results showed that CHS decreased growth performance and compromised the meat quality of broilers (p < 0.05). However, tributyrin supplementation improved ADG and FCR in broilers exposed to CHS (p < 0.05). Additionally, tributyrin supplementation resulted in increased shear force value and GSH-Px activity, as well as a decrease in drip loss, ether extract content, and MDA content of the breast muscle in broilers under CHS (p < 0.05). Furthermore, tributyrin supplementation up-regulated the mRNA expressions of Nrf2, NQO1, HO-1, SOD, and GSH-Px of the breast muscle in broilers exposed to CHS (p < 0.05). Based on these positive effects, the study delved deeper to investigate the impact of 0.16% tributyrin supplementation (HS + 0.16%T) on the cecum microbiota. The HS + 0.16%T treatment showed an increase in the relative abundance of Rikenellaceae_RC9_gut_group (p < 0.05) and a trend towards an increase in Lactobacillus (p = 0.096) compared to the HS treatment. The results indicate that supplementation successfully improved the growth performance and meat quality of Taihe silky fowls. Furthermore, tributyrin supplementation, particularly at levels of 0.16%, improved meat quality by enhancing muscle antioxidant capacity, which is believed to be associated with activation of the Nrf2 signaling pathway.

Atherosclerosis (AS) is considered the underlying cause of many diseases, particularly cardiovascular and cerebrovascular diseases. Inulin, a type of fructan, has shown potential in improving atherosclerosis, although there are conflicting findings. It is hypothesized that the polymerization degree of inulin may largely influence its therapeutic effectiveness. Therefore, this study aimed to investigate the effects and mechanisms of short-chain and long-chain inulin in AS.

ApoE-/- mice fed a high fat diet (HFD) were used to establish an atherosclerosis model. These mice received daily oral administration of either short-chain or long-chain inulin for 12 weeks. Plasma lipid metabolism-related indices were measured using biochemical analysis, and plasma immunological indices were analyzed via ELISA. The aorta, aortic root regions, liver tissue, adipose tissue, and colon tissue were examined through various staining techniques, including ORO staining, hematoxylin and eosin staining, Alcian blue staining, and immunofluorescent or immunohistochemical assays. Microbiome analysis was conducted in the cecal content.

The results indicated that both short-chain and long-chain inulin substantially reduced the formation of atherosclerotic plaques. Inulin also improved plasma lipid concentrations and hepatic lipid metabolism, and partially alleviated both localized (atherosclerotic lesions) and systemic inflammation. Short-chain inulin was more effective than long-chain inulin in reducing atherosclerotic plaques formation, enhancing lipid metabolism and reducing inflammation. Additionally, both types of inulin showed similar effectiveness in enhancing intestinal epithelial barrier integrity, gut microbiota composition and functionality.

These findings suggest that inulin has a protective role against atherosclerosis by enhancing lipid metabolism, reducing inflammation, and improving intestinal barrier and gut microbiota. As a dietary intervention, short-chain inulin is more effective than long-chain inulin, offering clinical implications for using inulin as a therapeutic agent for atherosclerosis.

Short-chain fatty acids (SCFAs) are major metabolites produced by the gut microbiota through the fermentation of dietary fiber, and they have garnered significant attention due to their close association with host health. As important mediators between the gut microbiota and the host, SCFAs serve as energy substrates for intestinal epithelial cells and maintain homeostasis in host immune and energy metabolism by influencing host epigenetics, activating G protein-coupled receptors, and inhibiting pathogenic microbial infections. This review provides a comprehensive summary of SCFAs synthesis and metabolism and offering an overview of the latest research progress on their roles in protecting gut health, enhancing energy metabolism, mitigating diseases such as cancer, obesity, and diabetes, modulating the gut-brain axis and gut-lung axis, and promoting bone health.

The escalating threat of antimicrobial resistance underscores the imperative for innovative therapeutic strategies. Host defense peptides (HDPs), integral components of innate immunity, exhibit profound antimicrobial and immunomodulatory properties. Various dietary compounds, such as short-chain fatty acids, vitamins, minerals, sugars, amino acids, phytochemicals, bile acids, probiotics, and prebiotics have been identified to enhance the synthesis of endogenous HDPs without provoking inflammatory response or compromising barrier integrity. Additionally, different classes of these compounds synergize in augmenting HDP synthesis and disease resistance. Moreover, dietary supplementation of several HDP-inducing compounds or their combinations have demonstrated robust protection in rodents, rabbits, pigs, cattle, and chickens from experimental infections. However, the efficacy of these compounds in inducing HDP synthesis varies considerably among distinct compounds. Additionally, the regulation of HDP genes occurs in a gene-specific, cell type-specific, and species-specific manner. In this comprehensive review, we systematically summarized the modulation of HDP synthesis and the mechanism of action attributed to each major class of dietary compounds, including their synergistic combinations, across a spectrum of animal species including humans. We argue that the ability to enhance innate immunity and barrier function without triggering inflammation or microbial resistance positions the nutritional modulation of endogenous HDP synthesis as a promising host-directed approach for mitigating infectious diseases and antimicrobial resistance. These HDP-inducing compounds, particularly in combinations, harbor substantial clinical potential for further exploration in antimicrobial therapies for both human and other animals.

In our earlier efforts to establish gut-brain axis during alcohol use disorder (AUD), we have demonstrated that supplementation of C57BL/6J male mice with 8 mg/mL sodium butyrate, a major short-chain fatty acid, in drinking water reduced ethanol intake and neuroinflammatory response in antibiotic (ABX)-enhanced voluntary binge-like alcohol consumption model, drinking in the dark (DID).

To further evaluate the preclinical potential of SB, we have set a dose-escalation study in C57BL/6J male mice to test effects of ad libitum 20 mg/mL SB and 50 mg/mL SB and their combinations with ABX in the DID procedure for 4 weeks. Effects of these SB concentrations on ethanol consumption and bodily parameters were determined for the duration of the treatments. At the end of study, blood, liver, and intestinal tissues were collected to study any potential adverse effects ad to measure blood ethanol concentrations.

Increasing SB concentrations in the drinking water caused a loss in the protective effect against ethanol consumption and produced adverse effects on body and liver weights, reduced overall liquid intake. The hypothesis that these effects were due to aversion to SB smell/taste at these high concentrations were further tested in a follow up proof-of-concept study with intragastric gavage administration of SB. The higher gavage dose (320 mg/kg) caused reduction in ethanol consumption without any adverse effects.

Overall, these findings added more support for the therapeutic potential of SB in management of AUD, given a proper form of administration.

In our earlier efforts to establish gut-brain axis during alcohol use disorder (AUD), we have demonstrated that supplementation of C57BL/6J male mice with 8 mg/mL sodium butyrate, a major short-chain fatty acid, in drinking water reduced ethanol intake and neuroinflammatory response in antibiotic (ABX)-enhanced voluntary binge-like alcohol consumption model, drinking in the dark (DID).

To further evaluate the preclinical potential of SB, we have set a dose-escalation study in C57BL/6J male mice to test effects of ad libitum 20 mg/mL SB and 50 mg/mL SB and their combinations with ABX in the DID procedure for 4 weeks. Effects of these SB concentrations on ethanol consumption and bodily parameters were determined for the duration of the treatments. At the end of study, blood, liver, and intestinal tissues were collected to study any potential adverse effects ad to measure blood ethanol concentrations.

Increasing SB concentrations in the drinking water caused a loss in the protective effect against ethanol consumption and produced adverse effects on body and liver weights, reduced overall liquid intake. The hypothesis that these effects were due to aversion to SB smell/taste at these high concentrations were further tested in a follow up proof-of-concept study with intragastric gavage administration of SB. The higher gavage dose (320 mg/kg) caused reduction in ethanol consumption without any adverse effects.

Overall, these findings added more support for the therapeutic potential of SB in management of AUD, given a proper form of administration.

Berberine (BBR), a well-known quaternary ammonium alkaloid, is recognized for its ability to prevent and alleviate metabolic disorders because of its anti-oxidative and anti-inflammatory properties. However, the underlying mechanisms of BBR to mitigate fatty liver hemorrhagic syndrome (FLHS) through the modulation of gut microbiota and their metabolism remained unclear. The results revealed that BBR ameliorates lipid metabolism disorder in high-energy and low-protein (HELP) diet-induced FLHS laying hens, as evidenced by improved liver function and lipid deposition of the liver, reduced blood lipids, and the expression of liver lipid synthesis-related factors. Moreover, BBR alleviated HELP diet-induced barrier dysfunction, increased microbial population, and dysregulated lipid metabolism in the ileum. BBR reshaped the HELP-perturbed gut microbiota, particularly declining the abundance of Desulfovibrio_piger and elevating the abundance of Bacteroides_salanitronis_DSM_18170. Meanwhile, metabolomic profiling analysis revealed that BBR reshaped microbial metabolism and function, particularly by reducing the levels of hydrocinnamic acid, dehydroanonaine, and leucinic acid. Furthermore, fecal microbiota transplantation (FMT) experiments revealed that BBR-enriched gut microbiota alleviated hepatic lipid deposition and intestinal inflammation compared with those chicks that received a gut microbiota by HELP. Collectively, our study provided evidence that BBR effectively alleviated FLHS induced by HELP by reshaping the microbial and metabolic homeostasis within the liver-gut axis.

Obesity is a chronic disease caused primarily by the imbalance between the amount of calories supplied to the body and energy expenditure. Not only does it deteriorate the quality of life, but most importantly it increases the risk of cardiovascular diseases and the development of type 2 diabetes mellitus, leading to reduced life expectancy. In this review, we would like to present the molecular pathomechanisms underlying obesity, which constitute the target points for the action of anti-obesity medications. These include the central nervous system, brain-gut-microbiome axis, gastrointestinal motility, and energy expenditure. A significant part of this article is dedicated to incretin-based drugs such as GLP-1 receptor agonists (e.g., liraglutide and semaglutide), as well as the brand new dual GLP-1 and GIP receptor agonist tirzepatide, all of which have become "block-buster" drugs due to their effectiveness in reducing body weight and beneficial effects on the patient's metabolic profile. Finally, this review article highlights newly designed molecules with the potential for future obesity management that are the subject of ongoing clinical trials.

Weaning is an important period in the growth and development of lambs. Thus, effectively reducing the occurrence of weaning stress is critical for maintaining lamb production. Coated sodium butyrate has been shown to reduce inflammation, promote intestinal health, and maintain homeostasis. However, the application and potential mechanism of coated sodium butyrate in alleviating weaning stress in lambs are still unclear. To evaluate the effects of coated sodium butyrate on the growth performance, antioxidant capacity, and gut microbiota of weaned lambs, 10 weaned lambs of 21-day-old were randomly divided into two groups: the CON group (basal diet) and the NaB group (basal diet +3 g/kg of coated sodium butyrate). The trial lasted 21 days. The experimental results showed that compared to the CON group, coated sodium butyrate supplementation in the diet significantly increased the average daily weight gain and daily feed intake of lambs (p < 0.05). In addition, compared to the CON group, the addition of coated sodium butyrate also significantly decreased the serum MDA level of lambs (p < 0.05). Notably, the addition of coated sodium butyrate did not have a significant effect on the cecal microbiota, while increasing the diversity of colonic microbiota and promoting the abundance of Lachnospiraceae, Verrucomicrobiota, Akkermansia, Roseburia, and Sinobacteraceae, which are associated with the nutrient absorption of lambs (p < 0.05). These results indicate that dietary supplementation with coated sodium butyrate could promote the growth and antioxidant capacity of weaned lambs and alleviate weaning stress.

Eating behavior is essential to human health. However, whether future eating behavior is subjected to the conditioning of preceding dietary composition is unknown. This study aimed to investigate the effect of dietary fiber consumption on subsequent nutrient-specific food preferences between palatable high-fat and high-sugar diets and explore its correlation with the gut microbiota. C57BL/6NJcl male mice were subjected to a 2-week dietary intervention and fed either a control (n = 6) or inulin (n = 6) diet. Afterward, all mice were subjected to a 3-day eating behavioral test to self-select from the simultaneously presented high-fat and high-sugar diets. The test diet feed intakes were recorded, and the mice's fecal samples were analyzed to evaluate the gut microbiota composition. The inulin-conditioned mice exhibited a preference for the high-fat diet over the high-sugar diet, associated with distinct gut microbiota composition profiles between the inulin-conditioned and control mice. The gut microbiota Oscillospiraceae sp., Bacteroides acidifaciens, and Clostridiales sp. positively correlated with a preference for fat. Further studies with fecal microbiota transplantation and eating behavior-related neurotransmitter analyses are warranted to establish the causal role of gut microbiota on host food preferences. Food preferences induced by dietary intervention are a novel observation, and the gut microbiome may be associated with this preference.

Short chain fatty acids (SCFAs), mainly including acetate, propionate and butyrate, are produced by intestinal bacteria during the fermentation of partially digested and indigestible polysaccharides. SCFAs play an important role in regulating intestinal energy metabolism and maintaining the homeostasis of the intestinal environment and also play an important regulatory role in organs and tissues outside the gut. In recent years, many studies have shown that SCFAs can regulate inflammation and affect host health, and two main signaling mechanisms have also been identified: the activation of G-protein coupled receptors (GPCRs) and inhibition of histone deacetylase (HDAC). In addition, a growing body of evidence highlights the importance of every SCFA in influencing health maintenance and disease development. In this review, we summarized the recent advances concerning the biological properties of SCFAs and their signaling pathways in inflammation and body health. Hopefully, it can provide a systematic theoretical basis for the nutritional prevention and treatment of human diseases.

β-Casomorphin-7 (BCM), a breakdown product of milk β-casein, exhibits opioid activity. Opioids are known to affect the immune system, but the effects of BCM on ulcerative colitis (UC) are not clear. We examined the effects of BCM on mucosal immunity using a mouse dextran sulfate sodium-induced colitis model and an in vitro CD8+ T cell activation model. Human UC patients were examined to reveal the relationship between CD10 and mucosal immunity. Combined treatment of the colitis model with thiorphan (TOP) inhibited BCM degradation by suppressing CD10 in the intestinal mucosa, activating mouse mucosal CD8, and suppressing CD4 and Treg. In the CD8+ T cell in vitro activation assay using mouse splenocytes, BCM inhibited the oxidative phosphorylation (OXPHOS) of CD8+ T cells and induced the glycolytic pathway, promoting their activation. Conversely, in a culture system, BCM suppressed OXPHOS and decreased defensin α production in IEC6 mouse intestinal epithelial cells. In the mouse model, BCM reduced defensin α and butyrate levels in the colonic mucosa. During the active phase of human ulcerative colitis, the downward regulation of ileal CD10 expression by CpG methylation of the gene promoter was observed, resulting in increased CD8 activation and decreased defensin α and butyrate levels. BCM is a potential aggravating factor for UC and should be considered in the design of dietary therapy. In addition, decreased CD10 expression may serve as an indicator of UC activity and recurrence, but further clinical studies are needed.

The influence of gut microbiota in the onset and development of several metabolic diseases has gained attention over the last few years. Diet plays an essential role in gut microbiota modulation. Western diet (WD), characterized by high-sugar and high-fat consumption, alters gut microbiome composition, diversity index, microbial relative levels, and functional pathways. Despite the promising health effects demonstrated by polyunsaturated fatty acids, their impact on gut microbiota is still overlooked. The effect of Fish oil (omega-3 source) and Pomegranate oil (punicic acid source), and a mixture of both oils in gut microbiota modulation were determined by subjecting the oil samples to in vitro fecal fermentations. Cecal samples from rats from two different dietary groups: a control diet (CD) and a high-fat high-sugar diet (WD), were used as fecal inoculum. 16S amplicon metagenomics sequencing showed that Fish oil + Pomegranate oil from the WD group increased α-diversity. This sample can also increase the relative abundance of the Firmicutes and Bacteroidetes phylum as well as Akkermansia and Blautia, which were affected by the WD consumption. All samples were able to increase butyrate and acetate concentration in the WD group. Moreover, tyrosine concentrations, a precursor for dopamine and norepinephrine, increase in the Fish oil + Pomegranate oil WD sample. GABA, an important neurotransmitter, was also increased in WD samples. These results suggest a potential positive impact of these oils' mixture on gut-brain axis modulation. It was demonstrated, for the first time, the great potential of using a mixture of both Fish and Pomegranate oil to restore the gut microbiota changes associated with WD consumption.

Maintaining an optimum microbial community within the gastrointestinal tract is intricately linked to human metabolic, immune and brain health. Disturbance to these microbial populations perturbs the production of vital bioactive compounds synthesised by the gut microbiome, such as short-chain fatty acids (SCFAs). Of the SCFAs, butyrate is known to be a major source of energy for colonocytes and has valuable effects on the maintenance of intestinal epithelium and blood brain barrier integrity, gut motility and transit, anti-inflammatory effects, and autophagy induction. Inducing endogenous butyrate production is likely to be beneficial for gut-brain homeostasis and for optimal neuronal function. For these reasons, butyrate has gained interest as a potential therapy for not only metabolic and immunological disorders, but also conditions related to the brain, including neurodegenerative diseases. While direct and indirect sources of butyrate, including prebiotics, probiotics, butyrate pro-drugs and glucosidase inhibitors, offer a promising therapeutic avenue, their efficacy and dosage in neurodegenerative conditions remain largely unknown. Here, we review current literature on effects of butyrate relevant to neuronal function, the impact of butyrate in a range of neurodegenerative diseases and related treatments that may have potential for the treatment of neurodegenerative diseases.

Maternal obesity and over/undernutrition can have a long-lasting impact on offspring health during critical periods in the first 1000 days of life. Children born to mothers with obesity have reduced immune responses to stimuli which increase susceptibility to infections. Recently, maternal western-style diets (WSDs), high in fat and simple sugars, have been associated with skewing neonatal immune cell development, and recent evidence suggests that dysregulation of innate immunity in early life has long-term consequences on metabolic diseases and behavioral disorders in later life. Several factors contribute to abnormal innate immune tolerance or trained immunity, including changes in gut microbiota, metabolites, and epigenetic modifications. Critical knowledge gaps remain regarding the mechanisms whereby these factors impact fetal and postnatal immune cell development, especially in precursor stem cells in bone marrow and fetal liver. Components of the maternal microbiota that are transferred from mothers consuming a WSD to their offspring are understudied and identifying cause and effect on neonatal innate and adaptive immune development needs to be refined. Tools including single-cell RNA-sequencing, epigenetic analysis, and spatial location of specific immune cells in liver and bone marrow are critical for understanding immune system programming. Considering the vital role immune function plays in offspring health, it will be important to understand how maternal diets can control developmental programming of innate and adaptive immunity.

Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts.

Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles.

These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. Video Abstract.

Gut microbiota(GM) have been proven associated with lots of gastrointestinal diseases, but its causal relationship with Gastroesophageal reflux disease(GERD) and Barrett's esophagus(BE) hasn't been explored. We aimed to uncover the causal relation between GM and GERD/BE and potential mediators by utilizing Mendelian Randomization(MR) analysis.

Summary statistics of GM(comprising 301 bacteria taxa and 205 metabolism pathways) were extracted from MiBioGen Consortium(N = 18,340) and Dutch Microbiome Project(N = 7,738), GERD and BE from a multitrait meta-analysis(NGERD=602,604, NBE=56,429). Bidirectional two-sample MR analysis and linkage disequilibrium score regression(LDSC) were used to explore the genetic correlation between GM and GERD/BE. Mediation MR analysis was performed for the risk factors of GERD/BE, including Body mass index(BMI), weight, type 2 diabetes, major depressive disorder(MDD), smoking initiation, alcohol consumption, and dietary intake(including carbohydrate, sugar, fat, protein intake), to detect the potential mediators between GM and GERD/BE.

11 bacterial taxa and 13 metabolism pathways were found associated with GERD, and 18 taxa and 5 pathways exhibited causal relationship with BE. Mediation MR analysis suggested weight and BMI played a crucial role in these relationships. LDSC identified 1 taxon and 4 metabolism pathways related to GERD, and 1 taxon related to BE. Specie Faecalibacterium prausnitzii had a suggestive impact on both GERD(OR = 1.087, 95%CI = 1.01-1.17) and BE(OR = 1.388, 95%CI = 1.03-1.86) and LDSC had determined their correlation. Reverse MR indicated that BE impacted 10 taxa and 4 pathways.

This study established a causal link between gut microbiota and GERD/BE, and identified the probable mediators. It offers new insights into the role of gut microbiota in the development and progression of GERD and BE in the host.

Recent evidence suggests that chronic exposure to opioid analgesics such as morphine disrupts the intestinal epithelial layer and causes intestinal dysbiosis. Depleting gut bacteria can preclude the development of tolerance to opioid-induced antinociception, suggesting an important role of the gut-brain axis in mediating opioid effects. The mechanism underlying opioid-induced dysbiosis, however, remains unclear. Host-produced antimicrobial peptides (AMPs) are critical for the integrity of the intestinal epithelial barrier as they prevent the pathogenesis of the enteric microbiota. Here, we report that chronic morphine or fentanyl exposure reduces the antimicrobial activity in the ileum, resulting in changes in the composition of bacteria. Fecal samples from morphine-treated mice had increased levels of Akkermansia muciniphila with a shift in the abundance ratio of Firmicutes and Bacteroidetes. Fecal microbial transplant (FMT) from morphine-naïve mice or oral supplementation with butyrate restored (a) the antimicrobial activity, (b) the expression of the antimicrobial peptide, Reg3γ, (c) prevented the increase in intestinal permeability and (d) prevented the development of antinociceptive tolerance in morphine-dependent mice. Improved epithelial barrier function with FMT or butyrate prevented the enrichment of the mucin-degrading A. muciniphila in morphine-dependent mice. These data implicate impairment of the antimicrobial activity of the intestinal epithelium as a mechanism by which opioids disrupt the microbiota-gut-brain axis.

Combined hyperlipidemia (CHL) manifests as elevated cholesterol and triglycerides, associated with fatty liver and cardiovascular diseases. Emerging evidence underscores the crucial role of the intestinal microbiota in metabolic disorders. However, the potential therapeutic viability of remodeling the intestinal microbiota in CHL remains uncertain. In this study, CHL was induced in low-density lipoprotein receptor-deficient (LDLR-/-) hamsters through an 8-week high-fat and high-cholesterol (HFHC) diet or a 4-month high-cholesterol (HC) diet. Placebo or antibiotics were administered through separate or cohousing approaches. Analysis through 16S rDNA sequencing revealed that intermittent antibiotic treatment and the cohousing approach effectively modulated the gut microbiota community without impacting its overall abundance in LDLR-/- hamsters exhibiting severe CHL. Antibiotic treatment mitigated HFHC diet-induced obesity, hyperglycemia, and hyperlipidemia, enhancing thermogenesis and alleviating nonalcoholic steatohepatitis (NASH), concurrently reducing atherosclerotic lesions in LDLR-/- hamsters. Metabolomic analysis revealed a favorable liver lipid metabolism profile. Increased levels of microbiota-derived metabolites, notably butyrate and glycylglycine, also ameliorated NASH and atherosclerosis in HFHC diet-fed LDLR-/- hamsters. Notably, antibiotics, butyrate, and glycylglycine treatment exhibited protective effects in LDLR-/- hamsters on an HC diet, aligning with outcomes observed in the HFHC diet scenario. Our findings highlight the efficacy of remodeling gut microbiota through antibiotic treatment and cohousing in improving obesity, NASH, and atherosclerosis associated with refractory CHL. Increased levels of beneficial microbiota-derived metabolites suggest a potential avenue for microbiome-mediated therapies in addressing CHL-associated diseases.

Vitamins are essential micronutrients that play key roles in many biological pathways associated with sepsis. The gut microbiome plays a pivotal role in the progression of sepsis and may contribute to the onset of multi-organ dysfunction syndrome (MODS). The aim of this study was to investigate the changes in serum vitamins, and their correlation with intestinal flora and metabolomic profiles in patients with sepsis.

The serum levels of vitamins were determined by Ultra Performance Liquid Chromatography (UPLC). 16S rRNA gene sequencing and Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) targeted metabolomics were used for microbiome and metabolome analysis.

In the training cohort: After univariate, multivariate (OPLS-DA) and Spearman analyses, it was concluded that vitamin levels of 25 (OH) VD3 and (VD2 + VD3), as well as vitamins A and B9, differed significantly among healthy controls (HC), non-septic critical patients (NS), and sepsis patients (SS) (P < 0.05). The validation cohort confirmed the differential vitamin findings from the training cohort. Moreover, analyses of gut flora and metabolites in septic patients and healthy individuals revealed differential flora, metabolites, and metabolic pathways that were linked to alterations in serum vitamin levels. We found for the first time that vitamin B9 was negatively correlated with g_Sellimonas.

Sepsis patients exhibited significantly lower levels of 25 (OH) VD3 and (VD2 + VD3), vitamins A and B9, which hold potential as predictive markers for sepsis prognosis. The changes in these vitamins may be associated with inflammatory factors, oxidative stress, and changes in gut flora.