Gut Microbiota Homeostasis Research Articles

Polysaccharides from soybean residue fermented by Neurospora crassa alleviate DSS-induced gut barrier damage and microbiota disturbance in mice.

Soluble polysaccharides derived from microbial fermentation of agricultural by-products were considered as potential functional ingredients, primarily having probiotic properties. Herein, soluble polysaccharides (FSRP) were isolated from soybean residue fermented by Neurospora crassa, and FSRP mainly contained rhamnose, arabinose, fucose, mannose, glucose, and galactose, according to GC-MS analysis. To further investigate the protective effect of FSRP against colitis, dextran sulfate sodium induction (DSS)-treated mice were orally gavaged with FSRP (200 mg kg-1 d-1) or inulin (400 mg kg-1 d-1, a positive control) for 7 d. The results showed that DSS-treated mice displayed symptoms of body weight loss, atrophy, and histopathological changes of colon, as well as gut barrier damage, which were recovered after FSRP supplementation (similar to inulin). Furthermore, the beneficial effects of FSRP were linked to a decreased inflammatory response and increased protein expression of E-cadherin, claudin-1 and ZO-1. Illumina-MiSeq sequencing analysis revealed that FSRP increased microbial diversity and altered community structure. Specifically, FSRP could modulate the abundance of inflammation-related bacteria (such as Tenericutes, Clostridia, and Bacilli) to ameliorate colitis symptoms. Therefore, FSRP can relieve DSS-induced colitis, which is closely associated with reduced levels of inflammatory factors, improved gut barrier function and gut microbiota homeostasis.

Effects of alkaloid-rich extracts obtained from Grifola frondosa on gut microbiota and glucose homeostasis in rats.

Grifola frondosa (GF), also known as maitake (a type of mushroom), has been widely used as a food item and it exhibits various health-beneficial hypoglycemic activities. Rats fed with a fat/high-sucrose-based diet were used to determine the hypoglycemic activity of 95% and 55% GF ethanol extracts (labeled as GF95 and GF55, respectively). The activity was determined by monitoring the fasting blood glucose level. Oral glucose tolerance tests were conducted, and the levels of alanine aminotransferase and aspartate aminotransferase were studied to study the hypoglycemic activity. The HPLC-ESI-TOF-MS technique was used to analyze the samples, and the results revealed that alkaloids were present in abundance in GF95 and GF55. It was also observed that GF55 contained some organic acids and GF95 contained extra small amounts of phenoloid. The levels of intestinal microbiota were analyzed, and the results from transcriptome analysis indicated that GF55 reduced the relative abundance of Romboutsia and affected RT-Db1, thereby improving the extent of glucose metabolism achieved. GF95 downregulated the mRNA level of Socs1 by increasing the levels of Oscillibacter, Butyricimonas, Barnesiella, Turicibacter, Methanosphaera, Asaccharobacter, Globicatella, Bifidobacterium, Allobaculum, and Romboutsia. The expression of Pik3rl was upregulated when the levels of Ruminococcus and Saccharibacteria increased. The hypoglycemic activity was induced under these conditions. The obtained data indicated that the efficiency of GF95 to control glucose levels was higher than the efficiency of GF55. This suggested that GF95 can be potentially used to protect against hyperglycemia.

Gestational Diabetes, Colorectal Cancer, Bariatric Surgery, and Weight Loss among Diabetes Mellitus Patients: A Mini Review of the Interplay of Multispecies Probiotics.

Diabetes mellitus has been steadily increasing over the past decades and is one of the most significant global public health concerns. Diabetes mellitus patients have an increased risk of both surgical and post-surgical complications. The post-surgical risks are associated with the primary condition that led to surgery and the hyperglycaemia per se. Gut microbiota seems to contribute to glucose homeostasis and insulin resistance. It affects the metabolism through body weight and energy homeostasis, integrating the peripheral and central food intake regulatory signals. Homeostasis of gut microbiota seems to be enhanced by probiotics pre and postoperatively. The term probiotics is used to describe some species of live microorganisms that, when administered in adequate amounts, confer health benefits on the host. The role of probiotics in intestinal or microbial skin balance after abdominal or soft tissue elective surgeries on DM patients seems beneficial, as it promotes anti-inflammatory cytokine production while increasing the wound-healing process. This review article aims to present the interrelation of probiotic supplements with DM patients undergoing elective surgeries.

Alginate oligosaccharides protect against fumonisin B1-induced intestinal damage via promoting gut microbiota homeostasis

Fumonisin B1 (FB1), one of the most common mycotoxins contaminating feed and food, has been shown to induce intestinal barrier degradation. However, its role on gut microbiota in this process is still unclear. Alginate oligosaccharides (AOS) have been reported to exert their anti-inflammatory and anti-apoptotic function partially via modulation the gut microbiota. However, little is known about the beneficial effect of AOS on gut microbiota upon FB1 exposure. Results show that FB1 degraded intestinal epithelial barrier function as evidenced by increased pathological epithelial cell shedding, reduced the number of goblet cells, and promoted intestinal cell apoptosis. Markedly, FB1 disturbed the cecal and fecal microbiota composition. FB1 increased the level of Lactobacillus and decreased the relative abundance of beneficial microbes. FB1 largely inhibited the production of short chain fatty acids (SCFAs). AOS greatly ameliorated FB1-induced intestinal damage, inflammation, and oxidative stress (eg., T-SOD and MDA). AOS alleviated gut microbial dysbiosis by promoting the growth of beneficial microbes such as Roseburia, Bifidobacterium, and Akkermansia, and increasing SCFAs production upon FB1 exposure. Moreover, the correlation analysis showed that FB1- and AOS-treated gut microbiota alteration is closely associated with the change of intestinal phenotype. We have thus provided a novel insight into the protective role of AOS on FB1-induced gut microbial dysbiosis.

Dietary Supplementation with Vitamin D, Fish Oil or Resveratrol Modulates the Gut Microbiome in Inflammatory Bowel Disease.

Gastrointestinal health is influenced by the functional genes and metabolites generated by the human microbiome. As the volume of current biomedical and translational research indicates, the importance and impact of this ecosystem of microorganisms, especially those comprising the gut microbiome on human health, has become increasingly apparent. Changes to the gut microbiome are associated with inflammatory bowel disease (IBD), which is characterized by persistent intestinal inflammation. Furthermore, the lifetime dietary choices of their host may positively or negatively affect both the gut microbiome and its impact on IBD. As such, “anti-inflammatory” dietary supplements, their impact, and mechanisms in restoring gut microbiota homeostasis during IBD is an area of intensive research. Dietary supplementation may represent an important adjuvant treatment avenue for limiting intestinal inflammation in IBD. Overall, this review addresses the development of the gut microbiome, the significance of the gut microbiome in IBD, and the use of dietary supplements such as vitamin D, fish oil, and resveratrol in the mitigation of IBD-associated gut dysbiosis and intestinal inflammation.

Metronidazole and ciprofloxacin differentially affect chronic unpredictable mild stress-induced changes in the colon, cecum and ileum microbiota.

Antibiotics have been shown to have a major impact on the composition and metabolism of gut microbiota, while unpredictable stress has been shown to have major influences on gut microbiota homeostasis. However, the impact of combination antibiotics (e.g. metronidazole and ciprofloxacin) on gut microbiota dysbiosis that is induced by stress remains unclear. Here, chronic unpredictable mild stress (CUMS) was used to simulate unpredictable stress, and Sprague-Dawley rats received antibiotics (metronidazole and ciprofloxacin) after CUMS. The weights and coefficients of the thymus, liver and spleen were analysed. 16S rRNA gene sequencing was performed to determine the gut microbiota in the colon, cecum and ileum. We found that antibiotics decreased the CUMS-induced increases in spleen coefficients. Short-term antibiotic exposure significantly increased the cecum and ileum microbiota richness and significantly increased the ileum microbiota diversity after CUMS. Long-term antibiotic exposure significantly decreased the colon microbiota diversity and significantly increased the ileum microbiota richness after CUMS. The impacts of antibiotic exposure on the microbiota compositions at the phylum and genus levels in different gut segments were different after CUMS. However, it is worth noting that the most differentially abundant bacteria in the colon, cecum and ileum were all Verrucomicrobia under long-term antibiotic exposure. Antibiotic exposure significantly increased the relative abundance of Lactobacillus in the colon and ileum and significantly increased the relative abundance of Akkermansia in the colon and cecum after CUMS. In conclusion, this study showed that metronidazole and ciprofloxacin differentially affected the CUMS-induced changes in the microbiota of the colon, cecum and ileum.Key points• The impacts of antibiotic exposure on the changes in microbiota that were induced by chronic unpredictable mild stress were analysed.• We collected rat gut microorganisms from the colon, cecum and ileum.• The diversities, compositions, functions and network structures were analysed.

Nitric Oxide Synthase Regulates Gut Microbiota Homeostasis by ERK-NF-κB Pathway in Shrimp.

The gut microbiota is a complex group of microorganisms that is not only closely related to intestinal immunity but also affects the whole immune system of the body. Antimicrobial peptides and reactive oxygen species participate in the regulation of gut microbiota homeostasis in invertebrates. However, it is unclear whether nitric oxide, as a key mediator of immunity that plays important roles in antipathogen activity and immune regulation, participates in the regulation of gut microbiota homeostasis. In this study, we identified a nitric oxide synthase responsible for NO production in the shrimp Marsupenaeus japonicus. The expression of Nos and the NO concentration in the gastrointestinal tract were increased significantly in shrimp orally infected with Vibrio anguillarum. After RNA interference of Nos or treatment with an inhibitor of NOS, L-NMMA, NO production decreased and the gut bacterial load increased significantly in shrimp. Treatment with the NO donor, sodium nitroprusside, increased the NO level and reduced the bacterial load significantly in the shrimp gastrointestinal tract. Mechanistically, V. anguillarum infection increased NO level via upregulation of NOS and induced phosphorylation of ERK. The activated ERK phosphorylated the NF-κB-like transcription factor, dorsal, and caused nuclear translocation of dorsal to increase expression of antimicrobial peptides (AMPs) responsible for bacterial clearance. In summary, as a signaling molecule, NOS-produced NO regulates intestinal microbiota homeostasis by promoting AMP expression against infected pathogens via the ERK-dorsal pathway in shrimp.

Is Gut Involvement a Cause or Effect of COVID-19?

Digestive disorder symptoms in COVID-19 may be similar in form to post-infectious functional gastrointestinal disorder (PI-FGID). To cause clinical effects, SARS-CoV-2 must reach the bowels and gastric hypochlorhydria may facilitate such transit. Asian elderly are predisposed to greater infection rate and severity of COVID-19, and the high prevalence of gastric atrophy and intake of proton-pump inhibitor in this aged group might explain the risk. Persistence shedding of SARS-CoV-2 in stools indicates that faecal transmission should not be disregarded. Gut involvement in COVID-19 is mediated by angiotensin-converting enzyme 2 (ACE2) receptor, which serves as the entry point for SARS-CoV-2 in the small bowel. ACE2 dysregulation has an impact on the homeostasis of gut microbiota and altered inflammatory response. Liver injury is variable in COVID-19 and is likely a result of by-stander effects rather than actual viropathic process. Further research is needed to understand if gut involvement is a cause or effect of SARS-CoV-2.

Sex-Specific Effects of Synbiotic Exposure in Mice on Addictive-Like Behavioral Alterations Induced by Chronic Alcohol Intake Are Associated With Changes in Specific Gut Bacterial Taxa and Brain Tryptophan Metabolism.

Chronic alcohol intake has been shown to disrupt gut microbiota homeostasis, but whether microbiota modulation could prevent behavioral alterations associated with chronic alcohol intake remains unknown. We investigated the effects of synbiotic dietary supplementation on the development of alcohol-related addictive behavior in female and male mice and evaluated whether these effects were associated with changes in bacterial species abundance, short-chain fatty acids, tryptophan metabolism, and neurotransmitter levels in the prefrontal cortex and hippocampus. Chronic intermittent exposure to alcohol during 20 days induced escalation of intake in both female and male mice. Following alcohol deprivation, relapse-like behavior was observed in both sexes, but anxiogenic and cognitive deficits were present only in females. Synbiotic treatment reduced escalation and relapse to alcohol intake in females and males. In addition, the anxiogenic-like state and cognitive deficits observed in females following alcohol deprivation were abolished in mice exposed to synbiotic. Alcohol-induced differential alterations in microbial diversity and abundance in both sexes. In females, synbiotic exposure abrogated the alterations provoked by alcohol in Prevotellaceae UCG-001 and Ruminococcaceae UCG-014 abundance. In males, synbiotic exposure restored the changes induced by alcohol in Akkermansia and Muribaculum uncultured bacterium abundance. Following alcohol withdrawal, tryptophan metabolites, noradrenaline, dopamine, and γ-aminobutyric acid concentrations in the prefrontal cortex and the hippocampus were correlated with bacterial abundance and behavioral alterations in a sex-dependent manner. These results suggested that a dietary intervention with a synbiotic to reduce gut dysbiosis during chronic alcohol intake may impact differently the gut-brain-axis in females and males.

Characterization of gut microbiota, metabolism and cytokines in benzene-induced hematopoietic damage

Benzene exposure leads to hematopoietic dysfunction and is characterized clinically by a decrease in blood cells, but the underlying mechanisms remain elusive. Disturbed gut microbiota may induce host metabolic, immune disorders and the onset of disease. However, the characterization of gut microbiota, metabolism, cytokines and their association with benzene-induced hematopoietic toxicity lacks systematic evidence. Here, the microbiomics, metabolomics and cytokine network were applied to find out the critical characteristics of gut microbiota, metabolism and cytokines in mice involved in the benzene-induced hematopoietic toxicity. We found that the decline in hematopoietic stem cells was earlier than the hematological changes in the 5 mg/kg and 25 mg/kg benzene exposure groups. While 125 mg/kg benzene exposure resulted in a significant decline in whole blood cells. High-throughput sequencing results showed that benzene exposure disrupted homeostasis of gut microbiota, metabolism and cytokine in mice. 6 bacteria, 12 plasma metabolites and 6 cytokines were associated with benzene-induced hematopoietic damage. Notably, IL-5 was significantly increased in benzene exposure group in a dose-dependent manner, and a significant negative correlation was found between IL-5 and hematopoietic damage. We further found that increased Family_XIII_AD3011_group at the genus level and decreased Anaerotruncus_sp at the species level in benzene-exposed group were strongly associated with hematopoietic toxicity and IL-5. Furthermore, the abundance of Family_XIII_AD3011_group and Anaerotruncus_sp were negatively correlated with Adipic acid and 4-Hydroxyproline, respectively. Our findings indicated that altered flora structure of gut microbiota affects the metabolic phenotype which acts as messengers for the gut microbes, affecting host inflammation. This preliminary study provides new insight into the potential mechanisms of benzene-induced hematopoietic toxicity, further exploration by functional studies is required in the future.

Dietary κ-carrageenan facilitates gut microbiota-mediated intestinal inflammation

The inflammatory effects of carrageenan (CGN), a ubiquitous food additive, remains controversial. Gut microbiota and intestinal homeostasis may be a breakthrough in resolving this controversy. Here we show that, κ-CGN did not cause significant inflammatory symptoms, but it did cause reduced bacteria-derived short-chain fatty acids (SCFAs) and decreased thickness of the mucus layer by altering microbiota composition. Administration of the pathogenic bacterium Citrobacter rodentium, further aggravated the inflammation and mucosal damage in the presence of κ-CGN. Mucus layer degradation and altered SCFA levels could be reproduced by fecal transplantation from κ-CGN-fed mice, but not from germ-free κ-CGN-fed mice. These symptoms could be partially repaired by administering probiotics. Our results suggest that κ-CGN may not be directly inflammatory, but it creates an environment that favors inflammation by perturbation of gut microbiota composition and then facilitates expansion of pathogens, and this effect may be partially reversed by the introduction of probiotics.

Curcumin ameliorated dextran sulfate sodium-induced colitis via regulating the homeostasis of DCs and Treg and improving the composition of the gut microbiota

Abnormal dendritic cells (DCs) and Treg cell polarisation and dysbiosis of the intestinal flora are typical features of the pathogenesis of inflammatory bowel disease (IBD). The natural compound curcumin has good anti-inflammatory properties. However, it is unclear whether curcumin effectively ameliorates IBD by regulating the homeostasis of DCs, Treg and gut microbiota. In this study, mice colitis induced by dextran sulfate sodium was orally administrated with curcumin (100 mg/kg/day) for 7 days. Consequently, the index of colonic weight significantly decreased, and body weight, colonic weight, colonic length and colonic tissue injury improved significantly; the percentage of Treg increased significantly, inflammatory DCs and pro-inflammatory cytokines decreased significantly, and the composition of gut microbiota were improved. In addition, curcumin inhibited the activation of PI3K/Akt signaling pathway in colitis mice. These data suggested that curcumin ameliorated colitis by regulating DCs, Treg and gut microbiota, and the underlying mechanism is related to PI3K/Akt pathway inhibition.

Comprehensive 16S rDNA Sequencing and LC-MS/MS-Based Metabolomics to Investigate Intestinal Flora and Metabolic Profiles of the Serum, Hypothalamus and Hippocampus in p‑Chlorophenylalanine-Induced Insomnia Rats Treated with Lilium brownie.

Gut microbiota homeostasis in the organism and insomnia have been reported to influence each other. In the study, a method of 16S rRNA gene sequencing combined with ultra-high performance liquid chromatography-mass/mass spectrometry was adopted to evaluate the effects of Lilium brownie (LB) on intestinal flora and metabolic profiles of serum, hypothalamus and hippocampus in insomnia rat induced by p‑chlorophenylalanine (PCPA). It was observed that the imbalance in the diversity and abundance of gut microbiota induced by PCPA was restored after LB intervention. Among these, the Porphyromonadaceae, Lactobacillus and Escherichia were significantly adjusted at the genus level by PCPA and LB, respectively. It was also found that the most of metabolic phenotypes in serum, hypothalamus and hippocampus perturbed by PCPA were regulated towards normal after LB intervention, especially 5-hydroxy-L-tryptophan of the hypothalamus involving in 5-HT metabolism. Moreover, the arachidonic acid metabolism in serum, hypothalamus and hippocampus, and the serotonergic synapse in hypothalamus and hippocampus were the most fundamentally and significantly affected pathways after LB intervention. The results of correlation analysis showed that several floras including Pseudoruegeria have an outstanding contribution to the change of differential metabolites. In brief, the results confirm that gut microbiota is significantly returned to normal and may interact with the corresponding metabolites to relieve insomnia under LB intervention.

Dietary lactoferrin has differential effects on gut microbiota in young versus middle-aged APPswe/PS1dE9 transgenic mice but no effects on cognitive function.

BackgroundExisting evidence suggest that lactoferrin might be beneficial for Alzheimer’s disease, while precise mechanisms are not fully elucidated.ObjectiveTo determine the effects of lactoferrin intervention on cognitive function from APPswe/PS1dE9 (APP/PS1) mice, and potential mechanisms involved.DesignBoth the young and middle-aged male APP/PS1 mice were divided into the control and lactoferrin intervention groups with 16 weeks’ intervention.ResultsLactoferrin had no effects on cognitive function for both the young and middle-aged mice, and no key markers involved in Aβ, tau pathology, neuro-inflammation and synaptic plasticity were altered after lactoferrin intervention. With regards to gut microbiota profiles, in the young APP/PS1 mice, lactoferrin elevated the α diversity index including ACE and Chao 1, and reduced the relative abundance of the genera Bacteroides and Alistipes and elevated Oscillibacter; in addition, Oscillibacter, Anaerotruncus, EF096579_g, EU454405_g, Mollicutes_RF39, EU474361_g, EU774448_g, and EF096976_g were specifically abundant via linear discriminant analysis with effect size (LEfSe) analysis. In the middle-aged APP/PS1 mice, the relative abundance of the phylum Proteobacteria, as well as the genera Oscillospira, Coprococcus, and Ruminococcus was significantly reduced post lactoferrin; additionally, S24_7, Bacteroidia, Bacteroidetes, and Methylobacterium were specific via LEfSe analysis in the lactoferrin group.ConclusionsDietary lactoferrin might be beneficial for gut microbiota homeostasis although it might have no effects on cognition.

Disruption of Intestinal Homeostasis Through Altered Responses of the Microbial Community, Energy Metabolites, and Immune System in Zebrafish After Chronic Exposure to DEHP.

Di-(2-ethylhexyl) phthalate (DEHP) is ubiquitously reported in global water bodies and exhibits various environmental and human health risks. However, the effects of DEHP chronic exposure on the intestinal microbiota and associated host health concerns in aquatic species are still largely unexplored. In this study, chronic exposure to DEHP at environmental levels significantly increased the body weight, length, and body mass index (BMI), especially in male fish. The microbial community was disrupted with the relative abundance of phylum Firmicutes and genera diversity for Prevotella-7, Deefgea, PeM15, Halomonas, Akkermansia, Chitinibacter, and Roseomonas, which are significantly activated in zebrafish after exposure to DEHP. The height of the gut villus, the thickness of muscularis layer, and the number of goblet cells per villus were significantly decreased, as well as showed differences between female and male zebrafish. Further, the levels of energy-related metabolites in gut tissues were increased, compared to the control group. The expression levels of immune-related genes (interleukin 8, il-8, also referred to as cxcl8a), microbial defense-related genes (lysozyme, lyz, interleukin 10, and il-10), and obesity-related genes (aquaporin 8a, aqp8, mucin 2.1, muc2.1, fibroblast growth factor 2, fgf2, and proopiomelanocortin a, pomca) were significantly up-regulated in zebrafish, except the down-regulated expressions of toll-like receptor-5 (tlr-5) and interleukin 1β (il-1β) in the females and pomca in the males, respectively. Importantly, Spearman’s correlation analyses revealed that the levels of metabolites and gene expressions in the gut were closely related to the dominant microbial genera, such as Aeromonas, Deefgea, Akkermansia, PeM15, Mycobacterium, and Rhodobacter. Taken together, chronic exposure to DEHP at environmental levels disturbed bacterial composition accompanied by the altered expressions of intestinal metabolites and the critical immune and intestinal function-related genes, which provided novel insights into DEHP effects on perturbation of gut microbiota and metabolic homeostasis in zebrafish.

Genetically encoded probiotic EcN 1917 alleviates alcohol-induced acute liver injury and restore gut microbiota homeostasis

Alcohol abuse increases the risk of acute liver injury. Escherichia coli Nissle 1917(EcN) has been comprehensively demonstrated as a safe oral probiotic. In this study, we genetically modified EcN expressing alcohol dehydrogenase gene, acetaldehyde dehydrogenase gene, NAD synthase gene, and NADH oxidase gene. Applied strains in the mouse experiment showed a 54.44% reduction in serum ethanol. EcN-treated mice also exhibited lower liver AST, ALT, MDA, TG, T-CHO, TNF-α, IL-1β and increased SOD and GSH levels versus untreated ones, indicating restored liver function alongside depressed oxidative stress, lipid peroxidation, and inflammation. Consistently, aberrant gene expression correlating with alcohol metabolism and injured liver induced by alcoholic food were restored following EcN inoculation. The efficacy EcN conferred was accompanied by the restoration of gut microbiota homeostasis. In conclusion, the engineered EcN has been shown to detoxify ethanol metabolites in liver disease models and which may be attributed to intestinal recovery.

Traditional Chinese Medicine Ganshuang Granules Attenuate CCl4 -Induced Hepatic Fibrosis by Modulating Gut Microbiota.

Gut dysbiosis contributes to hepatic fibrosis. Emerging evidence revealed the major role of traditional Chinese medicine (TCM) in gut microbiota homeostasis. Here, we aimed to investigate the anti-fibrotic activity and underlying mechanism of ganshuang granules (GS), particularly regarding gut microbiota homeostasis. CCl4 -induced hepatic fibrosis models were allocated into 4 groups receiving normal saline (model), 1.0, 2.0, or 4.0 g/kg GS for 5 weeks. As result, GS treatment alleviated liver injury in CCl4 -induced hepatic fibrosis, presenting as decreases of the liver index, alanine aminotransferase, and aspartate transaminase. Histological staining and expression revealed that the enhanced oxidative stress, inflammatory and hepatic fibrosis in CCl4 -induced models were attenuated by GS. Immunohistochemical staining showed that tight junction-associated proteins in intestinal mucosa were up-regulated by GS. 16S rRNA sequencing showed that GS rebalanced the gut dysbiosis manifested as improving alpha and beta diversity of gut microbiota, reducing the ratio of Firmicutes to Bacteroidetes, and regulating the relative abundance of various bacteria. In summary, GS decreased the intestinal permeability and rebalanced the gut microbiota to reduce the oxidative stress and inflammation, eventually attenuating CCl4 -induced hepatic fibrosis.

MicroRNA-602 prevents the development of inflammatory bowel diseases in a microbiota-dependent manner.

Inflammatory bowel diseases (IBD) are a group of chronic disorders occurring in the intestinal tract. Previous studies demonstrated that genetics and microbiota play critical roles in the pathogenesis of IBD. Discoveries of genes that may regulate the homeostasis of gut microbiota and pathogenesis of IBD have the potential to provide new therapeutic targets for IBD treatment. The results suggested that the expression level of microRNA (miR)-602 is negatively related to the development of IBD, and that miR-602 overexpression in mice may prevent inflammation and intestinal barrier injuries in dextran sulfate sodium (DSS)-induced IBD mice. It was also found that the microbiota is important for miR-602-mediated prevention of IBD, as the inhibitory effect of miR-602 was lost when the microbiota was depleted using antibiotics. Furthermore, co-housing or adoptive transfer of microbiota from miR-602 could attenuate the pathogenesis of IBD. In addition, it was demonstrated that miR-602 could target tumor necrosis factor receptor-associated factor 6 (TRAF6) in intestinal epithelial cells. Collectively, the present results suggest that miR-602 plays a protective role in DSS-induced IBD by targeting TRAF6 in a microbiota-dependent manner.

Dietary Bacillus subtilis supplementation alleviates alcohol-induced liver injury by maintaining intestinal integrity and gut microbiota homeostasis in mice.

Alcoholic liver disease (ALD) is a worldwide health problem with limited therapeutic options, which is associated with gut-derived endotoxins, particularly lipopolysaccharide (LPS) and intestinal microbiota dysbiosis. Recently, probiotics, synbiotics and other food additive interventions have been shown to be effective in decreasing or preventing the progression of ALD. Bacillus subtilis (B. subtilis) and its metabolic products are widely used as food additives to maintain intestinal health, but the protective effects of B. subtilis against alcohol-induced liver injury are poorly understood. In the present study a chronic alcohol-induced liver injury model was constructed based on the Lieber-DeCarli diet and it aimed to determine whether dietary B. subtilis supplementation may alleviate alcohol-induced liver injury. Results revealed that prophylactic B. subtilis supplementation partially restored gut microbiota homeostasis and relieved alcohol-induced intestinal barrier injury, which significantly decreased the translocation of bacterial endotoxins to the blood. In addition, the decreased serum LPS alleviated hepatic inflammation via the toll-like receptor 4 pathway, resulting in improved hepatic structure and function. These results demonstrated that dietary B. subtilis supplementation imparts novel hepatoprotective functions by improving intestinal permeability and homeostasis.

Composition-Activity Relationships of Polysaccharides from Saccharina japonica in Regulating Gut Microbiota in Short-Term High-Fat Diet-Fed Mice.

Saccharina japonica polysaccharide could modulate gut microbiota composition; however, the composition-activity relationship remains unclear, thus restricting its application. In the current study, we investigated the impact of eight different S. japonica polysaccharide fractions on the gut microbiota after day 2 and day 14 treatments on high-fat diet (HFD) feeding mice. The results showed that a 2 day HFD dramatically altered gut microbiota composition, and the additional 12 day HFD further strengthened the gut microbiota dysbiosis in the HFD group. LjA-1 and LjA-3 could partially alleviate the dysbiosis of gut microbiota composition and significantly alter gut microbiota function. Multiple linear regression analysis revealed that the sulfate content and the molecular weight distributions were the main factors affecting the dominant gut bacterial genera. Our findings reveal that gut microbiota homeostasis could be disordered by HFD at day 2 and provide insights into the quantitative composition-activity relationships of polysaccharides in regulating gut microbiota.