Gut microbiota contributes to bisphenol A-induced maternal intestinal and placental apoptosis, oxidative stress, and fetal growth restriction in pregnant ewe model by regulating gut-placental axis.

BACKGROUND: Bisphenol A (BPA) is an environmental contaminant with endocrine-disrupting properties that induce fetal growth restriction (FGR). Previous studies on pregnant ewes revealed that BPA exposure causes placental apoptosis and oxidative stress (OS) and decreases placental efficiency, consequently leading to FGR. Nonetheless, the response of gut microbiota to BPA exposure and its role in aggravating BPA-mediated apoptosis, autophagy, mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and OS of the maternal placenta and intestine are unclear in an ovine model of gestation. RESULTS: Two pregnant ewe groups (n = 8/group) were given either a subcutaneous (sc) injection of corn oil (CON group) or BPA (5 mg/kg/day) dissolved in corn oil (BPA group) once daily, from day 40 to day 110 of gestation. The maternal colonic digesta and the ileum and placental tissue samples were collected to measure the biomarkers of autophagy, apoptosis, mitochondrial dysfunction, ERS, and OS. To investigate the link between gut microbiota and the BPA-induced FGR in pregnant ewes, gut microbiota transplantation (GMT) was conducted in two pregnant mice groups (n = 10/group) from day 0 to day 18 of gestation after removing their intestinal microbiota by antibiotics. The results indicated that BPA aggravates apoptosis, ERS and autophagy, mitochondrial function injury of the placenta and ileum, and gut microbiota dysbiosis in pregnant ewes. GMT indicated that BPA-induced ERS, autophagy, and apoptosis in the ileum and placenta are attributed to gut microbiota dysbiosis resulting from BPA exposure. CONCLUSIONS: Our findings indicate the underlying role of gut microbiota dysbiosis and gut-placental axis behind the BPA-mediated maternal intestinal and placental apoptosis, OS, and FGR. The findings further provide novel insights into modulating the balance of gut microbiota through medication or probiotics, functioning via the gut-placental axis, to alleviate gut-derived placental impairment or FGR. Video Abstract.

Alanyl-Glutamine Dipeptide Attenuates Non-Alcoholic Fatty Liver Disease Induced by a High-Fat Diet in Mice by Improving Gut Microbiota Dysbiosis.

Non-alcoholic fatty liver disease (NAFLD) manifests as a persistent liver ailment marked by the excessive buildup of lipids within the hepatic organ accompanied by inflammatory responses and oxidative stress. Alanyl-glutamine (AG), a dipeptide comprising alanine and glutamine, is commonly employed as a nutritional supplement in clinical settings. This research aims to evaluate the impact of AG on NAFLD triggered by a high-fat diet (HFD), while concurrently delving into the potential mechanisms underlying its effects. The results presented herein demonstrate a notable reduction in the elevated body weight, liver mass, and liver index induced by a HFD upon AG administration. These alterations coincide with the amelioration of liver injury and the attenuation of hepatic histological advancement. Furthermore, AG treatment manifests a discernible diminution in oil-red-O-stained regions and triglyceride (TG) levels within the liver. Noteworthy alterations encompass lowered plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) concentrations, coupled with elevated high-density lipoprotein cholesterol (HDLC) concentrations. The mitigation of hepatic lipid accumulation resultant from AG administration is aligned with the downregulation of ACC1, SCD1, PPAR-γ, and CD36 expression, in conjunction with the upregulation of FXR and SHP expression. Concomitantly, AG administration leads to a reduction in the accumulation of F4/80-positive macrophages within the liver, likely attributable to the downregulated expression of MCP-1. Furthermore, AG treatment yields a decline in hepatic MDA levels and a concurrent increase in the activities of SOD and GPX. A pivotal observation underscores the effect of AG in rectifying the imbalance of gut microbiota in HFD-fed mice. Consequently, this study sheds light on the protective attributes of AG against HFD-induced NAFLD through the modulation of gut microbiota composition.

The Vegetable 'Kale' Protects against Dextran-Sulfate-Sodium-Induced Acute Inflammation through Moderating the Ratio of Proinflammatory and Anti-Inflammatory LPS-Producing Bacterial Taxa and Augmenting the Gut Barrier in C57BL6 Mice.

Kale (Brassica oleracea var. acephala), a food rich in bioactive phytochemicals, prevents diet-induced inflammation and gut dysbiosis. We hypothesized that the phytochemicals protect against the lipopolysaccharide (LPS)-induced acute inflammation which results from gut dysbiosis and loss of gut barrier integrity. We designed this study to test the protective effects of the whole vegetable by feeding C57BL/6J mice a rodent high-fat diet supplemented with or without 4.5% kale (0.12 g per 30 g mouse) for 2 weeks before administering 3% dextran sulfate sodium (DSS) via drinking water. After one week, DSS increased the representation of proinflammatory LPS (P-LPS)-producing genera Enterobacter and Klebsiella in colon contents, reduced the representation of anti-inflammatory LPS (A-LPS)-producing taxa from Bacteroidales, reduced the expression of tight junction proteins, increased serum LPS binding protein, upregulated molecular and histopathological markers of inflammation in the colon and shortened the colons. Mice fed kale for 2 weeks before the DSS regime had a significantly reduced representation of Enterobacter and Klebsiella and instead had increased Bacteroidales and Gram-positive taxa and enhanced expression of tight junction proteins. Downstream positive effects of dietary kale were lack of granuloma in colon samples, no shortening of the colon and prevention of inflammation; the expression of F4/80, TLR4 and cytokines 1L-1b, IL-6, TNF-a and iNOS was not different from that of the control group. We conclude that through reducing the proliferation of P-LPS-producing bacteria and augmenting the integrity of the gut barrier, kale protects against DSS-induced inflammation.

Oroxin B improves metabolic-associated fatty liver disease by alleviating gut microbiota dysbiosis in a high-fat diet-induced rat model.

Metabolic-associated fatty liver disease (MAFLD) has become a common chronic liver disease, but there is no FDA-approved drug for MAFLD treatment. Numerous studies have revealed that gut microbiota dysbiosis exerts a crucial effect on MAFLD progression. Oroxin B is a constituent of the traditional Chinese medicine Oroxylum indicum (L.) Kurz. (O. indicum), which has the characteristics of low oral bioavailability but high bioactivity. However, the mechanism through which oroxin B improves MAFLD by restoring the gut microbiota balance remains unclear. To this end, we assessed the anti-MAFLD effect of oroxin B in HFD-fed rats and investigated the underlying mechanism. Our results indicated that oroxin B administration reduced the lipid levels in the plasma and liver and lowered the lipopolysaccharide (LPS), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) levels in the plasma. Moreover, oroxin B alleviated hepatic inflammation and fibrosis. Mechanistically, oroxin B modulated the gut microbiota structure in HFD-fed rats by increasing the levels of Lactobacillus, Staphylococcus, and Eubacterium and decreasing the levels of Tomitella, Bilophila, Acetanaerobacterium, and Faecalibaculum. Furthermore, oroxin B not only suppressed Toll-like receptor 4-inhibitor kappa B-nuclear factor kappa-B-interleukin 6/tumor necrosis factor-α (TLR4-IκB-NF-κB-IL-6/TNF-α) signal transduction but also strengthened the intestinal barrier by elevating the expression of zonula occludens 1 (ZO-1) and zonula occludens 2 (ZO-2). In summary, these results demonstrate that oroxin B could alleviate hepatic inflammation and MAFLD progression by regulating the gut microbiota balance and strengthening the intestinal barrier. Hence, our study suggests that oroxin B is a promising effective compound for MAFLD treatment.

Cold-Brewed Jasmine Tea Attenuates High-Fat Diet-Induced Obesity and Gut Microbial Dysbiosis.

Cold-brewed jasmine tea (CB-JT) is regarded to possess characteristic flavors and health benefits as a novel resource of functional tea beverages. To investigate the molecular mechanisms underlying CB-JT-mediated protective effects on obesity, we evaluated the serum biochemistry, histological condition, glucose tolerance, gene expression profile and intestinal microbial diversity in high-fat diet (HFD)-fed mice. Our results demonstrate that cold-brewed jasmine tea can significantly attenuate HFD-induced body weight gain, abnormal serum lipid levels, fat deposition, hepatic injury, inflammatory processes as well as metabolic endotoxemia. CB-JT also modified the microbial community composition in HFD-fed mice and altered the balance to one closely resembled that of the control group. The differential abundance of core microbes in obese mice was reversed by CB-JT treatment, including an increment in the abundance of Blautia, Mucispirillum, and Bilophila as well as a decrease in the abundance of Alloprevotella. CB-JT was proved to regulate the mRNA expression levels of lipid metabolism-related genes such as Leptin, Pgc1a Il6, and Il1b in the adipose tissue coupled with Cyp7a1, Lxra, Srebp1c, and Atgl in the liver. These findings indicate that cold-brewed jasmine tea might be served as a potential functional tea beverage to prevent obesity and gut microbiota dysbiosis.

Puerariae lobatae Radix Alleviates Pre-Eclampsia by Remodeling Gut Microbiota and Protecting the Gut and Placental Barriers.

Pre-eclampsia (PE) is a serious pregnancy complication, and gut dysbiosis is an important cause of it. Puerariae lobatae Radix (PLR) is a medicine and food homologous species; however, its effect on PE is unclear. This study aimed to investigate the efficacy of PLR in alleviating PE and its mechanisms. We used an NG-nitro-L-arginine methyl ester (L-NAME)-induced PE mouse model to examine the efficacy of preventive and therapeutic PLR supplementation. The results showed that both PLR interventions alleviated hypertension and proteinuria, increased fetal and placental weights, and elevated the levels of VEGF and PlGF. Moreover, PLR protected the placenta from oxidative stress via activating the Nrf2/HO-1/NQO1 pathway and mitigated placental damage by increasing intestinal barrier markers (ZO-1, Occludin, and Claudin-1) expression and reducing lipopolysaccharide leakage. Notably, preventive PLR administration corrected gut dysbiosis in PE mice, as evidenced by the increased abundance and positive interactions of beneficial bacteria including Bifidobacterium, Blautia, and Turicibacter. Fecal microbiota transplantation confirmed that the gut microbiota partially mediated the beneficial effects of PLR on PE. Our findings revealed that modulating the gut microbiota is an effective strategy for the treatment of PE and highlighted that PLR might be used as an intestinal nutrient supplement in PE patients.

Selenium-Enriched Black Soybean Protein Prevents Benzo(a)pyrene-Induced Pyroptotic Colon Damage and Gut Dysbacteriosis.

Selenium-enriched black soybean protein (SeBSP) is a kind of high-quality selenium resource with many physiological functions. Benzo(a)pyrene (BaP) is a well-known injurant that widely exists in high-temperature processed food and has been previously found to cause colon injury. In this study, the effects of SeBSP on colonic damage induced by BaP in BALB/C mice were investigated by comparing it with normal black soybean protein (BSP). SeBSP inhibited the BaP-induced reductions on body weight, food intake, and water intake. Moreover, metabolic enzymes, including AhR, CYP1A1, CYP1B1, and GST-P1, that were promoted by BaP were downregulated by SeBSP, reducing oxidative damage caused by BaP in the metabolic process. The classical pyroptosis indexes (i.e., NLRP3, ASC, Caspase-1, GSDMD) and inflammatory factors (i.e., TNF-α, IL-1ß, IL-18, iNOS, COX-2) were downregulated by SeBSP in BaP-treated mice, suggesting the benefits of SeBSP in reducing colonic toxicity. Notably, SeBSP enhanced microbial diversity of gut microbiota and increased relative abundances of prebiotic bacteria, for example, Lactobacillus reuteri, Bacteroides thetaiotaomicron, and genera Bifidobacterium, and Blautia, along with the promotion of short-chain fatty acids. Integrative analysis showed strong links between the antioxidant and anti-inflammatory effects of SeBSP and its altered gut microbiota. Collectively, our study demonstrates the pronounced benefits of Se-enriched black soybean in preventing the colonic toxicity of BaP, and such effects could be mediated by gut microbiota.

The pharmacological validation of the Xiao-Jian-Zhong formula against ulcerative colitis by network pharmacology integrated with metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory bowel disease (IBD) is pathologically characterized by an immune response accommodative insufficiency and dysbiosis accompanied by persistent epithelial barrier dysfunction, and is divided into ulcerative colitis (UC) and Crohn's disease (CD). Its progression increases the susceptibility to colitis-associated cancer (CAC), as well as other complications. The Xiao-Jian-Zhong (XJZ) formula has a historical application in the clinic to combat gastrointestinal disorders. AIM OF THE STUDY: The investigation aimed to explore the molecular and cellular mechanisms of XJZ. MATERIALS AND METHODS: Dextran sodium sulfate (DSS) was diluted in drinking water and given to mice for a week to establish murine models of experimental colitis, and the XJZ solution was administered for two weeks. Network pharmacology analysis and weighted gene co-expression network analysis (WGCNA) were utilized to predict the therapeutic role of XJZ against UC and CAC. 16S rRNA sequencing and untargeted metabolomics were conducted utilizing murine feces to examine the changes in the microbiome profile. Biochemical experiments were conducted to confirm the predicted functions. RESULTS: XJZ treatment markedly attenuated DSS-induced experimental colitis progression, and the targets were enriched in inflammation, infection, and tumorigenesis, predicted by network pharmacology analysis. Based on The Cancer Genome Atlas (TCGA) database, the XJZ-targets were related to the survival probability in patients with colorectal cancer, underlying a potential therapeutic value in cancer intervention. Moreover, the XJZ therapy successfully rescued the decreased richness and diversity of microbiota, suppressed the potentially pathogenic phenotype of the gut microorganisms, and reversed the declined linoleic acid metabolism and increased cytochrome P450 activity in murine colitis models. Our in-vitro experiments confirmed that the XJZ treatment suppressed Caspase1-dependent pyroptosis and increased peroxisome proliferators-activated receptor-γ(PPAR-γ) expression in the colon, facilitated the alternative activation of macrophages (Mφs), inhibited tumor necrosis factor-α (TNFα)-induced reactive oxygen species (ROS) level in intestinal organoids (IOs), thereby favoring the mucosal healing. CONCLUSION: The XJZ formula is efficacious for colitis by a prompt resolution of inflammation and dysbiosis, and by re-establishing a microbiome profile that favors re-epithelization, and prevents carcinogenesis.

Moxibustion exhibits therapeutic effects on spinal cord injury via modulating microbiota dysbiosis and macrophage polarization.

In this study, we aimed to study the effect of moxibustion (MOX) on microbiota dysbiosis and macrophage polarization, so as to unveil the mechanism underlying the therapeutic effect of MOX in the management of spinal cord injury (SCI). SCI animal models were established to study the effect of MOX. Accordingly, it was found that MOX treatment significantly suppressed the Ace index and Shannon index in the SCI group. Moreover, the reduced relative levels of Lactobacillales and Bifidobacteriales and the elevated relative level of Clostridiales in the SCI animals were mitigated by the treatment of MOX. The body weight, food intake, energy expenditure (EE) index and respiratory quotient (RQ) index of SCI mice were all evidently decreased, but the levels of interleukin (IL)-17, interferon (IFN)-γ, monocyte chemoattractant protein-1 (MCP-1) and IL-1ß were increased in the SCI group. Moreover, MOX treatment significantly mitigated the dysregulation of above factors in SCI mice. Accordingly, we found that the Basso Mouse Scale (BMS) score was negatively correlated with the level of Clostridiales while positively correlated with the level of Lactobacillales. The apoptotic index and caspase-3 level were both evidently increased in the SCI group, while the SCI+MOX group showed reduced levels of apoptotic index and caspase-3. Therefore, it can be concluded that the treatment with MOX can promote microbiota dysbiosis and macrophage polarization, thus alleviating spinal cord injury by down-regulating the expression of inflammatory cytokines.

Saireito, a Japanese herbal medicine, alleviates leaky gut associated with antibiotic-induced dysbiosis in mice.

Antibiotics disrupt normal gut microbiota and cause dysbiosis, leading to a reduction in intestinal epithelial barrier function. Disruption of the intestinal epithelial barrier, which is known as "leaky gut", results in increased intestinal permeability and contributes to the development or exacerbation of gastrointestinal diseases such as inflammatory bowel disease and irritable bowel syndrome. We have previously reported on a murine model of intestinal epithelial barrier dysfunction associated with dysbiosis induced by the administration of ampicillin and vancomycin. Saireito, a traditional Japanese herbal medicine, is often used to treat autoimmune disorders including ulcerative colitis; the possible mechanism of action and its efficacy, however, remains unclear. In this study, we examined the efficacy of Saireito in our animal model for leaky gut associated with dysbiosis. C57BL/6 mice were fed a Saireito diet for the entirety of the protocol (day1-28). To induce colitis, ampicillin and vancomycin were administered in drinking water for the last seven consecutive days (day22-28). As previously demonstrated, treatment with antibiotics caused fecal occult bleeding, cecum enlargement with black discoloration, colon inflammation with epithelial cell apoptosis, and upregulation of pro-inflammatory cytokines. Oral administration of Saireito significantly improved antibiotics-induced fecal occult bleeding and cecum enlargement by suppressing inflammation in the colon. Furthermore, Saireito treatment ensured the integrity of the intestinal epithelial barrier by suppressing apoptosis and inducing cell adhesion proteins including ZO-1, occludin, and E-cadherin in intestinal epithelial cells, which in turn decreased intestinal epithelial permeability. Moreover, the reduced microbial diversity seen in the gut of mice treated with antibiotics was remarkably improved with the administration of Saireito. In addition, Saireito altered the composition of gut microbiota in these mice. These results suggest that Saireito alleviates leaky gut caused by antibiotic-induced dysbiosis. Our findings provide a potentially new therapeutic strategy for antibiotic-related gastrointestinal disorders.

Bacteroides fragilis Supplementation Deteriorated Metabolic Dysfunction, Inflammation, and Aorta Atherosclerosis by Inducing Gut Microbiota Dysbiosis in Animal Model.

BACKGROUND: The gut microbial ecosystem is an important factor that regulates host health and the onset of chronic diseases, such as inflammatory bowel diseases, obesity, hyperlipidemia, and diabetes mellitus, which are important risk factors for atherosclerosis. However, the links among diet, microbiota composition, and atherosclerotic progression are unclear. METHODS AND RESULTS: Four-week-old mice (-/- mice, C57Bl/6) were randomly divided into two groups, namely, supplementation with culture medium (control, CTR) and Bacteroides fragilis (BFS), and were fed a high-fat diet. The gut microbiota abundance in feces was evaluated using the 16S rDNA cloning library construction, sequencing, and bioinformatics analysis. The atherosclerotic lesion was estimated using Oil Red O staining. Levels of CD36, a scavenger receptor implicated in atherosclerosis, and F4/80, a macrophage marker in small intestine, were quantified by quantitative real-time PCR. Compared with the CTR group, the BFS group showed increased food intake, fasting blood glucose level, body weight, low-density lipoprotein level, and aortic atherosclerotic lesions. BFS dramatically reduced Lactobacillaceae (LAC) abundance and increased Desulfovibrionaceae (DSV) abundance. The mRNA expression levels of CD36 and F4/80 in small intestine and aorta tissue in the BFS group were significantly higher than those in the CTR group. CONCLUSIONS: gut microbiota dysbiosis was induced by BFS. It was characterized by reduced LAC and increased DSV abundance and led to the deterioration of glucose/lipid metabolic dysfunction and inflammatory response, which likely promoted aorta plaque formation and the progression of atherosclerosis.

Mechanistic Insights into the Link between Gut Dysbiosis and Major Depression: An Extensive Review.

Depression is a highly common mental disorder, which is often multifactorial with sex, genetic, environmental, and/or psychological causes. Recent advancements in biomedical research have demonstrated a clear correlation between gut dysbiosis (GD) or gut microbial dysbiosis and the development of anxiety or depressive behaviors. The gut microbiome communicates with the brain through the neural, immune, and metabolic pathways, either directly (via vagal nerves) or indirectly (via gut- and microbial-derived metabolites as well as gut hormones and endocrine peptides, including peptide YY, pancreatic polypeptide, neuropeptide Y, cholecystokinin, corticotropin-releasing factor, glucagon-like peptide, oxytocin, and ghrelin). Maintaining healthy gut microbiota (GM) is now being recognized as important for brain health through the use of probiotics, prebiotics, synbiotics, fecal microbial transplantation (FMT), etc. A few approaches exert antidepressant effects via restoring GM and hypothalamus-pituitary-adrenal (HPA) axis functions. In this review, we have summarized the etiopathogenic link between gut dysbiosis and depression with preclinical and clinical evidence. In addition, we have collated information on the recent therapies and supplements, such as probiotics, prebiotics, short-chain fatty acids, and vitamin B12, omega-3 fatty acids, etc., which target the gut-brain axis (GBA) for the effective management of depressive behavior and anxiety.

The Human Gut Microbiome as a Potential Factor in Autism Spectrum Disorder.

The high prevalence of gastrointestinal (GI) disorders among autism spectrum disorder (ASD) patients has prompted scientists to look into the gut microbiota as a putative trigger in ASD pathogenesis. Thus, many studies have linked the gut microbial dysbiosis that is frequently observed in ASD patients with the modulation of brain function and social behavior, but little is known about this connection and its contribution to the etiology of ASD. This present review highlights the potential role of the microbiota-gut-brain axis in autism. In particular, it focuses on how gut microbiota dysbiosis may impact gut permeability, immune function, and the microbial metabolites in autistic people. We further discuss recent findings supporting the possible role of the gut microbiome in initiating epigenetic modifications and consider the potential role of this pathway in influencing the severity of ASD. Lastly, we summarize recent updates in microbiota-targeted therapies such as probiotics, prebiotics, dietary supplements, fecal microbiota transplantation, and microbiota transfer therapy. The findings of this paper reveal new insights into possible therapeutic interventions that may be used to reduce and cure ASD-related symptoms. However, well-designed research studies using large sample sizes are still required in this area of study.

Distinct effects of TU-100 (daikenchuto) on long-lasting dysbiosis in the small intestine in patients with colorectal cancer and inflammatory bowel disease.

The profile of the human small intestinal microbiota remains to be uncovered primarily due to sampling difficulties. Ileostomy provides the intestinal luminal contents as ileostomy effluents (IE) that offer opportunity for performing extensive analyses of nutrients, gastrointestinal fluids, metabolites, and microbiome. In the present study, we evaluated changes in the microbiome, pH, and bacterial short-chain fatty acids (SCFAs) in IE obtained from patients who had undergone ileostomy following surgical resection of colon cancer and inflammatory bowel disease (IBD). We enrolled 11 patients who varied in the duration of ileostomy from 3 days to >5 years after surgery and had no inflammation in the small intestine. The analyses suggested that IE from patients previously having IBD had less diversity and greater intraday and interday fluctuations, and increased pH and decreased levels of propionic acid and acetic acid than those in IE from patients previously having cancer. Furthermore, correlation analysis suggested a possible effect of the intestinal microbiome on luminal pH, presumably via SCFA production. The present study suggested that inflammation in the colon may induce long-term dysbiosis in the small intestine even after removal of diseased parts of the colon. Moreover, pharmaceutical-grade Japanese traditional medicine daikenchuto (TU-100) was found to have beneficial effects on postoperative bowel dysfunction and the human small intestinal microbiota. Taken together, these results suggest the necessity of a direct remedy for dysbiosis and the treatment of gastrointestinal lesions to achieve favorable outcomes for chronic gastrointestinal disorders.

Alpha-Ketoglutarate Attenuates Colitis in Mice by Increasing Lactobacillus Abundance and Regulating Stem Cell Proliferation via Wnt-Hippo Signaling.

SCOPE: Inflammatory bowel disease is an inflammatory gastrointestinal disorder associated with intestinal barrier damage, cell proliferation disorder, and dysbiosis of the intestinal microbiota. It remains unknown whether alpha-ketoglutarate (α-KG) can alleviate colitis in mice. METHODS AND RESULTS: Six-week-old male C57BL/6 mice supplemented with or without 0.5% α-KG (delivered in the form of sodium salt) are subjected to drinking water or 2.5% DSS to induce colitis. The results show that α-KG administration is attenuated the severity of colitis, as is indicated by reduced body-weight loss, colon shortening and colonic hyperplasia, and repressed proinflammatory cytokine secretion in DSS-challenged mice. Additionally, DSS-induced increases in malondialdehyde (MDA) and hydrogen peroxide (H2 O2 ), and decreases in glutathione (GSH) levels are attenuated by α-KG administration. Further study shows that the protective effect of α-KG is associated with restoring gut barrier integrity by enhancing the expression of tight junction proteins, increasing Lactobacillus levels, and regulating gut hyperplasia by the Wnt-Hippo signaling pathway in DSS-induced colitis. CONCLUSION: Collectively, the data provided herein demonstrate that α-KG administration is attenuated mucosal inflammation, barrier dysfunction, and gut microflora dysbiosis. This beneficial effect is associated with increased Lactobacillus levels and regulated colon hyperplasia by the Wnt-Hippo signaling pathway.

Rhubarb Enema Increasing Short-Chain Fatty Acids that Improves the Intestinal Barrier Disruption in CKD May Be Related to the Regulation of Gut Dysbiosis.

The incidence of CKD seriously endangers people's health. Researchers have proposed that improving the intestinal barrier damage in CKD may be an effective target for delaying the progression of CKD. Rhubarb can effectively improve the intestinal barrier and renal fibrosis, which may be related to the regulation of gut dysbiosis, but the mechanism needs to be further studied. Short-chain fatty acids (SCFAs) are important metabolites of the gut microbiota and play an important role in maintaining the intestinal barrier. The purpose of this study was to investigate whether rhubarb enema regulates the production of short-chain fatty acid-related gut microbiota and improves the intestinal barrier damage of CKD. 5/6 nephrectomy rats were used as the animal model, sevelamer was used as the positive control group, and the sham operation rats were used as the control group. After 4 weeks of enema treatment, the general clinical indicators, short-chain fatty acid levels, renal pathology, intestinal tissue pathology, intestinal tight junction protein, and changes in gut microbiota were detected. The results showed that rhubarb enema can increase the level of short-chain fatty acids in the 5/6 nephrectomy model rats, improve the intestinal barrier damage, inhibit the decrease of intestinal tight junction proteins, reduce inflammation levels, improve kidney pathology, reduce blood creatinine levels, and regulate the intestinal tract, the abundance, and composition of the flora. Further correlation analysis showed that rhubarb enema increased the level of short-chain fatty acids in 5/6 nephrectomy model rats, which may be related to the 7 strains that may regulate the production of short-chain fatty acids. This study indicated that rhubarb enema can improve the intestinal barrier damage of 5/6 nephrectomy model rats and improve CKD, which may be related to the regulation of short-chain fatty acid-producing gut microbiota.

Microbiome Crosstalk in Immunotherapy and Antiangiogenesis Therapy.

The human body and its microbiome constitute a highly delicate system. The gut microbiome participates in the absorption of the host's nutrients and metabolism, maintains the microcirculation, and modulates the immune response. Increasing evidence shows that gut microbiome dysbiosis in the body not only affects the occurrence and development of tumors but also tumor prognosis and treatment. Microbiome have been implicated in tumor control in patients undergoing anti- angiogenesis therapy and immunotherapy. In cases with unsatisfactory responses to chemotherapy, radiotherapy, and targeted therapy, appropriate adjustment of microbes abundance is considered to enhance the treatment response. Here, we review the current research progress in cancer immunotherapy and anti- angiogenesis therapy, as well as the unlimited potential of their combination, especially focusing on how the interaction between intestinal microbiota and the immune system affects cancer pathogenesis and treatment. In addition, we discuss the effects of microbiota on anti-cancer immune response and anti- angiogenesis therapy, and the potential value of these interactions in promoting further research in this field.

Anti-inflammatory effects of purple sweet potato anthocyanin extract in DSS-induced colitis: modulation of commensal bacteria and attenuated bacterial intestinal infection.

Purple sweet potato anthocyanins have been acknowledged for their beneficial effects on human inflammatory bowel diseases (IBD). Although the ability of anthocyanins in modulating the gut microbiota has been reported, the relationship between the bacteria modulated by anthocyanins and intestinal inflammation has not been fully elucidated. We aimed to ascertain whether the purple sweet potato anthocyanin extract (PSPAE) modulation of gut microbiota in the dextran sodium sulphate (DSS) induced chronic colitis mouse model could result in the maintenance of intestinal homeostasis and protection against bacterial intestinal inflammation. Chronic colitis was induced by adding DSS in drinking water while administering the mice with PSPAE via gavage (20 mg kg-1). Effects on colon tissue damage, gut microbiota composition, tight junction protein, and cytokines were evaluated. PSPAE prevented the loss of Bifidobacterium and Lactobacillus and inhibited the increase of Gammaproteobacteria and Helicobacter upon DSS treatment. The non-pathogenic-dependent and pathogenic-dependent microenvironments were established upon treatment with broad-spectrum antibiotics. Both PSPAE treatment and non-pathogenic treatments modified the colonic expression of mouse tight junction proteins and maintained the architecture of the colon. However, the non-pathogenic treatment could not attenuate intestinal inflammation. Moreover, the pathogenic-dependent dysbiosis was exacerbated because of the increasing colonization of pathogens such as Helicobacter. The PSPAE exerted the modulation of gut microbiota to maintain the gut microbiome homeostasis in DSS-induced chronic colitis mice, which may help to propose a new treatment that combines efficacy and reduction of the possibility of bacterial intestinal infection.

Gut microbiota disorder caused by diterpenoids extracted from Euphorbia pekinensis aggravates intestinal mucosal damage.

Gut microbiota disorder will lead to intestinal damage. This study evaluated the influence of total diterpenoids extracted from Euphorbia pekinensis (TDEP) on gut microbiota and intestinal mucosal barrier after long-term administration, and the correlations between gut microbiota and intestinal mucosal barrier were analysed by Spearman correlation analysis. Mice were randomly divided to control group, TDEP groups (4, 8, 16 mg/kg), TDEP (16 mg/kg) + antibiotic group. Two weeks after intragastric administration, inflammatory factors (TNF-α, IL-6, IL-1ß) and LPS in serum, short chain fatty acids (SCFAs) in feces were tested by Enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), respectively. The expression of tight junction (TJ) protein in colon was measured by western blotting. Furthermore, the effects of TDEP on gut microbiota community in mice have been investigated by 16SrDNA high-throughput sequencing. The results showed TDEP significantly increased the levels of inflammatory factors in dose-dependent manners, and decreased the expression of TJ protein and SCFAs, and the composition of gut microbiota of mice in TDEP group was significantly different from that of control group. When antibiotics were added, the diversity of gut microbiota was significantly reduced, and the colon injury was more serious. Finally, through correlation analysis, we have found nine key bacteria (Barnesiella, Muribaculaceae_unclassified, Alloprevotella, Candidatus_Arthromitus, Enterorhabdus, Alistipes, Bilophila, Mucispirillum, Ruminiclostridium) that may be related to colon injury caused by TDEP. Taken together, the disturbance of gut microbiota caused by TDEP may aggravate the colon injury, and its possible mechanism may be related to the decrease of SCFAs in feces, disrupted the expression of TJ protein in colon and increasing the contents of inflammatory factors.

The synergy of dietary supplements Lactobacillus salivarius LI01 and Bifidobacterium longum TC01 in alleviating liver failure in rats treated with D-galactosamine.

Lactobacillus salivarius (L. salivarius) has been widely used in dietary supplements and clinical treatments. Previous studies demonstrated the protective effect of L. salivarius LI01 on liver injury induced by D-galactosamine (D-GaIN) in rats. Accumulating evidence indicates that Lactobacillus and Bifidobacterium are highly coordinated; so in this study, we focus on the synergistic effect of L. salivarius LI01 and B. longum TC01 on the alleviation of liver injury caused by D-GaIN in rats and aim to find out the underlying interaction between the two strains. We observed reduced hepatic damage in the D-GaIN-treated rats with probiotic pre-administration, characterized by lower levels of AST and ALT (p < 0.05) and decreased HAI (Histological Activity Index) scores. Moreover, cotreatment with LI01 and TC01 more effectively decreases proinflammatory cytokines TNF-α, MCP-1 and M-CSF (p < 0.05) so as to inhibit systemic inflammation. Gut barrier dysfunction was ameliorated with compound probiotic pretreatment, as evidenced by the ultrastructure integrity, decreased histological score and elevated TJP-1 expression. What's more, supplementation with LI01 and TC01 markedly alleviates gut dysbiosis in the G-DaIN-treated rats, with enrichment of short chain fatty acid (SCFA) producers Faecalibaculum and Eubacterium_xylanophilum_group, a decreased Firmicutes/Bacteroidetes (F/B) ratio and depletion of proinflammatory microbes, such as Peptococcaeae and Ruminococcaceae_UCG-005. This study highlights the synergistic effect of dietary supplements LI01 and TC01 on the protection against liver failure, which is probably via altering gut microbiota.