Gut Microbiota Community Research Articles

Gut dysbiosis promotes prostate cancer progression and docetaxel resistance via activating NF-κB-IL6-STAT3 axis

BackgroundThe gut microbiota is reportedly involved in the progression and chemoresistance of various human malignancies. However, the underlying mechanisms behind how it exerts some effect on prostate cancer, as an extra-intestinal tumor, in a contact-independent way remain elusive and deserve exploration. Antibiotic exposure, one of the various factors affecting the gut microbiota community and capable of causing gut dysbiosis, is associated with multiple disorders. This study aims to preliminarily clarify the link between gut dysbiosis and prostate cancer.ResultsFirst, we discovered that perturbing the gut microbiota by consuming broad-spectrum antibiotics in water promoted the growth of subcutaneous and orthotopic tumors in mice. Fecal microbiota transplantation could transmit the effect of antibiotic exposure on tumor growth. Then, 16S rRNA sequencing for mouse feces indicated that the relative abundance of Proteobacteria was significantly higher after antibiotic exposure. Meanwhile, intratumoral lipopolysaccharide (LPS) profoundly increased under the elevation of gut permeability. Both in vivo and in vitro experiments revealed that the NF-κB-IL6-STAT3 axis activated by intratumoral LPS facilitated prostate cancer proliferation and docetaxel chemoresistance. Finally, 16S rRNA sequencing of patients’ fecal samples revealed that Proteobacteria was enriched in patients with metastatic prostate cancer and was positively correlated with plasma IL6 level, regional lymph node metastasis status, and distant metastasis status. The receiver operating characteristic (ROC) curves showed that the relative abundance of Proteobacteria had better performance than the prostate-specific antigen (PSA) level in predicting the probability of distant metastasis in prostate cancer (area under the ROC curve, 0.860; p < 0.001).ConclusionCollectively, this research demonstrated that gut dysbiosis, characterized by the enrichment of Proteobacteria due to antibiotic exposure, resulted in the elevation of gut permeability and intratumoral LPS, promoting the development of prostate cancer via the NF-κB-IL6-STAT3 axis in mice. Considering findings from human patients, Proteobacteria might act as an intestinal biomarker for progressive prostate cancer.8Rvk2m_7VYdxXtFw33rTopVideo

Altitude-adaption of gut microbiota in Tibetan chicken

Low oxygen levels and extremely cold weather in high-altitude environments requires more energy intake to maintain body temperature in animals. However, little is known about the characteristics of cecal and ileac microbiota in Tibetan chicken and how the high and low altitude environments affect the gut microbiota communities in Tibetan chicken. In the present study, In the present study, Tibetan chickens (Group HA, 3572 m, 578.5 Pa) and their introduced flatland counterparts (Group LA, 580 m, 894.6 Pa) in the cecum and ileum to identify the possible bacterial species that are helpful for their host in environmental adaption. High-throughput sequencing was used to sequence the V3 to V4 hypervariable regions of the bacterial 16S rRNA gene. By comparing the gut microbial diversity of HA chicken with that of LA, the results indicated that the microbial diversity of the cecum and ileum in group HA was significantly lower (P < 0.05) than those in group LA. The cecum microbiome maintained higher population diversity and richness than the ileum (P < 0.05). Four phyla Firmicutes, Bacterioidetes, Actinobacteria, and Proteobacteria were dominant in two groups. Interestingly, there were significant differences in abundance ratio among the four groups (P < 0.05). The predominant bacteria in HA and LA ileum belong to Proteobacteria and Firmicutes, whereas in cecum, Bacterioidetes and Actinobacteria were predominant in both groups (P < 0.05). Correlation analysis showed that Sporosarcina, Enterococcus, and Lactococcus were strongly related to air pressure, and Peptoclostridium and Ruminococcaceae_UCG-014 are related to altitude and gut microbiota of LA group was influenced by altitude, while HA group affected by air pressure. Meanwhile, the Ruminococcus-torques-group was negatively correlated with the relative abundance of Paenibacillus, and positive correlated with those of other microorganisms. Furthermore, HA has higher abundance of microbiota involved in energy and glycan biosynthesis metabolism pathway, while LA has higher abundance of microbiota involved in membrane transport, signal transduction, and xenobiotics biodegradation and metabolism. Generally, our results suggested that the composition and diversity of gut microbes changed after Tibetan chickens were introduced to the plain. Tibetan chicken may adapt to new environment via reshaping the gut microbiota. Gut microbes may contribute to the host adaption to high altitude environments by increasing host energy and glycan biosynthesis.

Alterations of Gut Microbiome and Metabolite Profiles Associated With Anabatic Lipid Dysmetabolism in Thyroid Cancer.

BackgroundCurrently, the high morbidity of individuals with thyroid cancer (TC) is an increasing health care burden worldwide. The aim of our study was to investigate the relationship among the gut microbiota community, metabolites, and the development of differentiated thyroid cancer.Methods16S rRNA gene sequencing and an integrated LC–MS-based metabolomics approach were performed to obtain the components and characteristics of fecal microbiota and metabolites from 50 patients with TC and 58 healthy controls (HCs).ResultsThe diversity and richness of the gut microbiota in the TC patients were markedly decreased. The composition of the gut microbiota was significantly altered, and the Bacteroides enterotype was the dominant enterotype in TC patients. Additionally, the diagnostic validity of the combined model (three genera and eight metabolites) and the metabolite model (six metabolites) were markedly higher than that of the microbial model (seven genera) for distinguishing TC patients from HCs. LEfSe analysis demonstrated that genera (g_Christensenellaceae_R-7_group, g_Eubacterium_coprostanoligenes_group) and metabolites [27-hydroxycholesterol (27HC), cholesterol] closely related to lipid metabolism were greatly reduced in the TC group. In addition, a clinical serum indicator (total cholesterol) and metabolites (27HC and cholesterol) had the strongest influence on the sample distribution. Furthermore, functional pathways related to steroid biosynthesis and lipid digestion were inhibited in the TC group. In the microbiota-metabolite network, 27HC was significantly related to metabolism-related microorganisms (g_Christensenellaceae_R-7_group).ConclusionsOur research explored the characteristics of the gut microecology of patients with TC. The findings of this study will help to discover risk factors that affect the occurrence and development of TC in the intestinal microecology.

Alarmins and innate lymphoid cells 2 activation: A common pathogenetic link connecting respiratory syncytial virus bronchiolitis and later wheezing/asthma?

Severe respiratory syncytial virus (RSV) infection in infancy is associated with increased risk of recurrent wheezing in childhood. Both acute and long-term alterations in airway functions are thought to be related to inefficient antiviral immune response. The airway epithelium, the first target of RSV, normally acts as an immunological barrier able to elicit an effective immune reaction but may also be programmed to directly promote a Th2 response, independently from Th2 lymphocyte involvement. Recognition of RSV transcripts and viral replication intermediates by bronchial epithelial cells brings about release of TSLP, IL-33, HMGB1, and IL-25, dubbed "alarmins." These epithelial cell-derived proteins are particularly effective in stimulating innate lymphoid cells 2 (ILC2) to release IL-4, IL-5, and IL-13. ILC2, reflect the innate counterparts of Th2 cells and, when activate, are potent promoters of airway inflammation and hyperresponsiveness in RSV bronchiolitis and childhood wheezing/asthma. Long-term epithelial progenitors or persistent epigenetic modifications of the airway epithelium following RSV infection may play a pathogenetic role in the short- and long-term increased susceptibility to obstructive lung diseases in response to RSV in the young. Additionally, ILC2 function may be further regulated by RSV-induced changes in gut microbiota community composition that can be associated with disease severity in infants. A better understanding of the alarmin-ILC interactions in childhood might provide insights into the mechanisms characterizing these immune-mediated diseases and indicate new targets for prevention and therapeutic interventions.

Guar Gum-Induced Changes in Gut Microbiota Metabolic Activity and Intestinal Immune Response Augments Susceptibility to Experimental Colitis

ObjectivesGuar gum is a common food additive found in many processed foods. Both preclinical and clinical studies documented the beneficial effect of guar gum on gastrointestinal health. We, therefore, hypothesized that guar gum might attenuate the severity of ulcerative colitis (UC), an inflammatory bowel disease (IBD) that chiefly affects the large intestine.MethodsTo test the effect of guar gum on colitis, wild-type (WT) mice were fed diets containing either cellulose (insoluble fiber as control) or guar gum (soluble fiber, 7.5% w/w) for four weeks. Acute and chronic colitis was induced via epithelial injury [dextran sulfate sodium (DSS, 1.4% w/v) in drinking water for 7 days] or immune hyperactivation [IL-10 receptor neutralization by weekly injections of αIL-10R mAb (1 mg/mouse, intraperitoneally) for 4 weeks], respectively. Colitis development was examined by serological, biochemical, histological, and immunological parameters.ResultsUnexpectedly, experimental mice maintained on a guar gum-containing diet (GuD) exhibited increased susceptibility to both acute and chronic colitis. Relative to the control group, GuD-fed mice experienced greater occurrence of rectal bleeding, diarrhea, splenomegaly, and displayed higher levels of pro-inflammatory markers [serum amyloid A (SAA) and lipocalin 2 (Lcn2)]. Analysis of the composition of gut microbiota and their metabolites revealed elevated branched chain amino acids and reduced butyrate in the GuD-fed groups compared to control, among other differences in gut microbiota community structure. Depletion of gut microbiota with broad spectrum antibiotics reversed colitis susceptibility, suggesting that GuD-induced alterations in gut microbiota might contribute to the severity of experimental colitis. Besides differences in gut microbiota activity, a substantial decrease in colonic IL-18 production (>3 folds) was observed in mice fed GuD. Remarkably, supplementation of recombinant IL-18 (rIL-18) alleviated colitis in GuD-fed mice, suggesting that reduced colonic IL-18 upon GuD feeding increases susceptibility to colitis.ConclusionsCollectively, our study demonstrates that food additive guar gum adversely impacts the gut microbiota activity and colonic immune response and increases susceptibility to colonic inflammation.Funding SourcesCrohn's & Colitis Foundation.

Gut microbiota-derived ursodeoxycholic acid from neonatal dairy calves improves intestinal homeostasis and colitis to attenuate extended-spectrum β-lactamase-producing enteroaggregative Escherichia coli infection

BackgroundAntimicrobials are often used to prevent and treat diarrhea induced by enteroaggregative Escherichia coli (EAEC) in young ruminants. However, drug overuse or misuse accelerates the spread of multidrug-resistant extended-spectrum β-lactamase (ESBL)-producing E. coli. Thus, supplementary foods as alternatives to antibiotics are needed to prevent colibacillus diarrhea in neonatal dairy calves. Ursodeoxycholic acid (UDCA), a therapeutic bile acid, helps alleviate colitis. However, how UDCA helps alleviate ESBL-EAEC-induced clinical symptoms and colitis remains unclear.ResultsWe investigated the microbial profiles and metabolites of healthy and diarrheic neonatal calves to determine microbial and metabolite biomarkers in early-life development. Both the gut microbiota communities and their associated metabolites differed between healthy and diarrheic calves. Commensal Butyricicoccus, Faecalibacterium, Ruminococcus, Collinsella, and Coriobacterium were key microbial markers that distinguished healthy and diarrheic gut microbiomes. Random forest machine-learning algorithm and Spearman correlation results indicated that enriched UDCA, short-chain fatty acids (SCFAs), and other prebiotics were strongly positively correlated with these five bacterial genera. We explored the effect of ursodiol on bacterial growth, cell adherence, and lipopolysaccharide-treated Caco-2 cells. Adding ursodiol induced direct antibacterial effects, suppressed proinflammatory effects, and reduced cell integrity damage. Oral ursodiol delivery to neonatal mice exhibited significant antibacterial effects and helped maintain colonic barrier integrity in mouse models of peritonitis sepsis and oral infection. UDCA supplementation attenuated colitis and recovered colonic SCFA production. To validate this, we performed fecal microbiota transplantations to inoculate ESBL-EAEC-infected neonatal mice. Microbiotas from UDCA-treated neonatal mice ameliorated colitis and hindgut commensal bacterial damage compared with that of the microbiotas from the control and placebo mice, as evidenced by colonization of abundant bacteria, including Oscillospiraceae, Ruminococcaceae, Lachnospiraceae, and Clostridia_UCG-014, and upregulated SCFA production.ConclusionsThis study provided the first evidence that UDCA could confer diarrhea resistance in ESBL-EAEC-infected newborn dairy calves. UDCA blocked bacterial growth and invasion both in vitro and in vivo, alleviated commensal bacterial dysbiosis during ESBL-EAEC infection in neonatal mouse models of sepsis and colitis via the TGR5-NF-κB axis, and upregulated SCFA production in the hindgut digesta. Our findings provide insight into the UDCA-mediated remission of ESBL-EAEC infections and the potential role of UDCA as an antibiotic alternative.4w5amkFjBAcdG8aZG5NrJ4Video abstract

Effects of Bile Acid Modulation by Dietary Fat, Cholecystectomy, and Bile Acid Sequestrant on Energy, Glucose, and Lipid Metabolism and Gut Microbiota in Mice.

Bile acid metabolism, involved with the digestion and absorption of nutrients in the gut, is linked to the gut microbiota community, greatly impacting the host’s metabolism. We examined the hypothesis that the modulation of bile acid metabolism by dietary fat contents, gallbladder removal (GBX; cholecystectomy), and bile acid sequestrant (BAS; cholestyramine) treatment could alter energy, glucose, and lipid metabolism through the changes in the gut microbiota. Mice were randomly assigned to the following six groups: (1) Sham GBX surgery (Sham) + low fat/high carbohydrate diet (LFD), (2) Sham + high fat diet (HFD), (3) Sham + HFD + BAS, (4) GBX + LFD, (5) GBX + HFD, and (6) GBX + HFD + BAS. BAS groups received 2% cholestyramine. After an 8-week intervention, energy, glucose, and lipid metabolism, and the gut microbiota community were measured. HFD groups exhibited higher body weight gain than LFD, and GBX increased the weight gain comped to Sham groups regardless of BAS in HFD (p < 0.05). Homeostatic model assessment for insulin resistance (HOMA-IR) was higher in HFD than LFD, and GBX increased it regardless of BAS. Serum lipid profiles were worsened in GBX + HFD compared to Sham + LFD, whereas BAS alleviated them, except for serum HDL cholesterol. Hepatic tumor-necrosis-factor-α (TNF-α) mRNA expression and lipid peroxide contents increased with GBX and BAS treatment compared to Sham and no BAS treatment (p < 0.05). Hepatic mRNA expression of sterol regulatory element-binding transcription factor 1c (SREBP1c) and peroxisome proliferator-activated receptor gamma (PPAR-γ) exhibited the same trend as that of tumor necrosis factor-α (TNF-α). The α-diversity of gut bacteria decreased in GBX + HFD and increased in GBX + HFD + BAS. Akkermentia, Dehalobacterium, SMB53, and Megamonas were high in the Sham + LFD, and Veillonella and Streptococcus were rich in the Sham + HFD, while Oscillospira and Olsenella were high in Sham + HFD + BAS (p < 0.05). GBX + LFD increased Lactobacillus and Sutterella while GBX + HFD + BAS elevated Clostridium, Alistipes, Blautia, Eubacterium, and Coprobacillus (p < 0.05). In conclusion, the modulation of bile acid metabolism influences energy, glucose, and lipid metabolisms, and it might be linked to changes in the gut microbiota by bile acid metabolism modulation.

The Stance4Health Project: Evaluating a Smart Personalised Nutrition Service for Gut Microbiota Modulation in Normal- and Overweight Adults and Children with Obesity, Gluten-Related Disorders or Allergy/Intolerance to Cow's Milk.

Unhealthy diets represent a major risk for the pathogenesis of metabolic and chronic inflammatory diseases. Improving the quality of diet is important to prevent chronic diseases, and diet-induced modifications of the gut microbiota (GM) community likely play an important role. The EU-funded Stance4Health project aims at performing a randomized clinical trial based on a nutritional intervention program in the context of normal weight and overweight adults as well as children with obesity and gluten-related disorders or allergy/intolerance to cow’s milk. The trial will evaluate the efficacy of a Smart Personalised Nutrition (SPN) service in modifying GM composition and metabolic function and improving consumer empowerment through technology adoption.

Effects of chronic exposure to the fungicide vinclozolin on gut microbiota community in an aquatic turtle

Environmental issues associated with the widespread use of agricultural chemicals are being seriously concerned. Of them, toxicological impacts of fungicides in aquatic organisms are often overlooked. Here, soft-shelled turtle (Pelodiscus sinensis) hatchlings were exposed to different concentrations of vinclozolin (0, 5, 50, 500 and 5000 μg/L) for 60 days to investigate the impact of fungicide exposure on their gut microbial composition and diversity. Vinclozolin exposure significantly affected the composition of the gut microbiota in hatchling turtles. Unexpectedly, gut bacterial diversity and richness of vinclozolin-exposed turtles (but not for the 5000 μg/L-exposed group) were relatively higher than control ones. At the phylum level, the abundance of Firmicutes was decreased, while that of Proteobacteria was increased in high-concentration groups. At the genus level, some bacterial genera including Cellulosilyticum, Romboutsia and Clostridium_sensu_stricto, were significantly changed after vinclozolin exposure; and some uniquely observed in high-concentration groups. Gene function predictions showed that genes related to amino acid metabolism were less abundant, while those related to energy metabolism more abundant in high-concentration groups. The prevalence of some pathogens inevitably affected gut health status of vinclozolin-exposed turtles. Such gut microbiota dysbiosis might be potentially linked with hepatic metabolite changes induced by vinclozolin exposure.

Integrated Gut-Heart Axis and Network Pharmacology to Reveal the Mechanisms of the Huoxue Wentong Formula Against Myocardial Ischemia.

Background Myocardial ischemia (MI) is a major public health problem with high mortality and morbidity worldwide. Huoxue Wentong formula (HX), a traditional Chinese medicine (TCM) formula, exhibits unambiguous effects on treating MI and preventing cardiovascular diseases. However, the molecular mechanism of the therapeutic effects of HX on MI remains largely unknown. Objective This study combined microbiology, metabolomics, and network pharmacology to explore the relationship between the gut microbiota and its metabolites in MI rats and the efficacy of HX. Methods First, the MI rat model was established by ligation of left anterior descending. Echocardiography, Masson's staining, and hematoxylin and eosin staining were used to evaluate the effect of HX on MI. Then, fecal metabolomics and 16S rRNA sequencing were used to obtain the microbial and metabolic characteristics of HX on MI. After that, network pharmacology was used to predict the target and action pathway of HX in treating MI. Finally, the relationship between fecal metabolites and target was explored through bioinformatics. Results HX can improve the cardiac function and ameliorated myocardial fibrosis in MI rats. Moreover, HX can affect the gut microbiota community and metabolites of MI rats, especially Bacteroides, Deferribacteres, Ruminococcus_sp._zagget7, Acidobacteria, daidzein, L-lactic acid, and malate. Network pharmacology found that HX can function through tumor necrosis factor (TNF), tumor protein p53 (TP53), interleukin 6 (IL6), vascular endothelial growth factor A (VEGFA), fos proto-oncogene (FOS), bcl2-associated X (BAX), myeloperoxidase (MPO), PI3K-Akt signaling pathways, and HIF-1 signaling pathway. The mechanism study showed that the anti-MI effect of HX was related to valine, leucine, and isoleucine biosynthesis, fatty acid biosynthesis, and arachidonic acid metabolism. Conclusion This study demonstrates that HX treated MI rats in a multitarget and multipathway manner. Its mechanism is related to the change of gut microbiota and the regulation of valine, leucine and isoleucine biosynthesis, fatty acid biosynthesis, and arachidonic acid metabolism.

Dietary Cholesterol‐Induced Gut Microbes Drive Nonalcoholic Fatty Liver Disease Pathogenesis in a Murine Model

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are hepatic manifestations of metabolic syndrome and major indications for liver transplantation. Western diet contributes to disease pathogenesis, partially mediated through the gut microbiome, yet mechanisms remain elusive. Human epidemiological studies identified high dietary cholesterol intake as a NAFLD risk factor and it is essential to drive disease in murine models, yet little is known about its role in reshaping gut microbiota. Using the fast food (FF) diet murine model in germ‐free (GF) mice completely devoid of all microbes and their conventionally‐raised (control) counterparts harboring complex microbiomes, we hypothesized high dietary cholesterol‐induced gut microbiota impact NAFLD onset, progression, and severity.Male C57Bl/6 age‐matched GF and control mice were fed 1 of 4 semi‐purified diets: low‐fat (LF); high fat (HF); FF + 0.2% high cholesterol (FFHC); FF + 2% very high cholesterol (FFVHC) for 8 or 24 weeks. Fecal gut microbiota profiles were tracked over time via Illumina MiSeq 16S rRNA gene amplicon sequencing. Serum alanine transaminase (ALT) and lipopolysaccharide binding protein (LBP, an indicator of gut barrier function) were measured throughout the study. Livers were collected for histology and Illumina NovaSeq RNA‐sequencing.Despite equal caloric intake between GF and controls across diets, significant weight gain and increased liver weight to body weight ratios (P&lt;0.05) were observed only in control mice fed FF diets. GF mice were largely protected from disease, with no elevation in plasma ALT, LBP, or histology‐based NAFLD activity score (NAS) regardless of treatment. Conversely, FFVHC control mice exhibited significantly elevated plasma ALT after 8 weeks on diet, which was exacerbated at 24 weeks relative to LF control and all GF groups. FF diets significantly increased (FFHC: P&lt;0.05; FFVHC: P&lt;0.01) plasma LBP after 24 weeks. Control mice fed FF diets exhibited severe steatosis, where FFVHC significantly increased NAS at 8 (P&lt;0.05) and 24 (P&lt;0.001) weeks relative to LF control and all GF groups. Microbiota profiling revealed no change in α‐diversity regardless of diet in control mice. β‐diversity analysis showed HF and FF diets, particularly FFVHC, rapidly shifted gut microbiota community membership after only 4 weeks, preceding disease onset and was further exacerbated over time. Liver RNA‐seq revealed FFVHC diet in control, but not GF, mice significantly enriched genes involved in the KEGG pathway, “antigen processing and presentation” (Bonferroni P&lt;0.001) relative to HF‐fed counterparts at 24 weeks.Taken together, FF diet‐induced shifts in gut microbes are both a prerequisite for and precede NAFLD/NASH disease onset, which is exacerbated by increased dietary cholesterol, driving liver inflammation. These data provide unique insights into how Western diet components impact host‐microbe interactions in complex liver diseases, which may aid in identifying novel therapeutic interventions.

Gut microbiota promote biotransformation and bioaccumulation of arsenic in tilapia

Aquatic organisms such as fish can accumulate high levels of arsenic (As) and transform toxic inorganic As (iAs) to non-toxic arsenobetaine (AsB). Whether the gut microbiota are involved in the process of As accumulation and transformation in fish is unclear. Herein, we subjected tilapia (Oreochromis mossambicus) to antibiotic treatment for 19 d to remove the gut microbiota, followed by the dietary exposure to arsenate (As(V)) for 16 d. The antibiotic-treated fish accumulated significantly less total As and AsB levels in the intestine and muscle than the fish in the control group. The gut contents (mixture of microbiota, digestive fluid, and diet debris) in the control fish metabolized As(V) to arsenite (As(III)) and organoarsenicals in vitro, while those in the antibiotic-treated fish lost this ability. As(V) exposure significantly changed the fish gut microbiota community. Stenotrophomonas maltophilia was found to be the dominant species (>60% of total operational taxonomic unit (OTU) number) in the gut microbiota of As-treated fish. The isolated As-resistant strain S. maltophilia SCSIOOM owned a high capability to metabolize As(V) to As(III) and organoarsenicals. Overall, these results demonstrated that the gut microbiota, at least the As-resistant bacteria, were involved in As biotransformation pathways in fish.

Exploring the Gut Microbiome in Myasthenia Gravis.

The human gut microbiota is vital for maintaining human health in terms of immune system homeostasis. Perturbations in the composition and function of microbiota have been associated with several autoimmune disorders, including myasthenia gravis (MG), a neuromuscular condition associated with varying weakness and rapid fatigue of the skeletal muscles triggered by the host’s antibodies against the acetylcholine receptor (AChR) in the postsynaptic muscle membrane at the neuromuscular junction (NMJ). It is hypothesized that perturbation of the gut microbiota is associated with the pathogenesis of MG. The gut microbiota community profiles are usually generated using 16S rRNA gene sequencing. Compared to healthy individuals, MG participants had an altered gut microbiota’s relative abundance of bacterial taxa, particularly with a drop in Clostridium. The microbial diversity related to MG severity and the overall fecal short-chain fatty acids (SCFAs) were lower in MG subjects. Changes were also found in terms of serum biomarkers and fecal metabolites. A link was found between the bacterial Operational Taxonomic Unit (OTU), some metabolite biomarkers, and MG’s clinical symptoms. There were also variations in microbial and metabolic markers, which, in combination, could be used as an MG diagnostic tool, and interventions via fecal microbiota transplant (FMT) could affect MG development. Probiotics may influence MG by restoring the gut microbiome imbalance, aiding the prevention of MG, and lowering the risk of gut inflammation by normalizing serum biomarkers. Hence, this review will discuss how alterations of gut microbiome composition and function relate to MG and the benefits of gut modulation.

Bacterial Atlas of Mouse Gut Microbiota

Background. Mouse model is one of the most widely used animal models for exploring the roles of human gut microbiota, a complex system involving in human immunity and metabolism. However, the structure of mouse gut bacterial community has not been explored at a large scale. To address this concern, the diversity and composition of the gut bacteria of 600 mice were characterized in this study. Results. The results showed that the bacteria belonging to 8 genera were found in the gut microbiota of all mouse individuals, indicating that the 8 bacteria were the core bacteria of mouse gut microbiota. The dominant genera of the mouse gut bacteria contained 15 bacterial genera. It was found that the bacteria in the gut microbiota were mainly involved in host’s metabolisms via the collaborations between the gut bacteria. The further analysis demonstrated that the composition of mouse gut microbiota was similar to that of human gut microbiota. Conclusion. Our study presented a bacterial atlas of mouse gut microbiota, providing a solid basis for investing the bacterial communities of mouse gut microbiota.

Blastocystis sp. Subtypes Colonisation and their Association with Clinical Diseases: A Systematic Review

Blastocystis sp. has been considered as an opportunistic intestinal parasite particularly in immunocompromised patient. Recent findings of the predominance of Blastocystis subtypes infection in the clinical disease with its interaction with gut microbiota in the hosts will be discussed accordingly. A total of 57 eligible studies, published from 2010 to October 2020 from a broad search in electronic databases were accessed. The studies showed that bloating, abdominal pain and diarrhoea were among the common symptoms in Blastocystis sp. infection in the immunocompromised patients. However, asymptomatic and healthy individuals were also infected by the Blastocystis sp. with higher prevalence among healthy individuals. Specifically, Blastocystis sp. ST3 were most frequently discovered among immunocompromised patients (IBS, cancer, transplant, HIV/AIDS, dengue) followed by ST1 and ST2. Despite most studies suggesting that Blastocystis sp. promote a healthy gut, a few studies had suggested otherwise. Blastocystis sp. colonisation may modify the gut microbiota with the reduction of beneficial bacteria phyla such as Firmicutes and Bacteroides. Although there was a positive association between Blastocystis sp. subtypes and clinical diseases, more studies are needed. To understand the pathogenicity of Blastocystis sp., their interactions with the gut microbiota communities in humans are properly discussed.

The impact of environmental pH on the gut microbiota community structure and short chain fatty acid production.

Environmental pH is a critical parameter for maintenance of the gut microbiota. Here, the impact of pH on the gut microbiota luminal and mucosal community structure and short chain fatty acid (SCFA) production was evaluated in vitro, and data compiled to reveal a donor-independent response to an increase or decrease in environmental pH. The results found that raising environmental pH significantly increased luminal community richness and decreased mucosal community evenness. This corresponded with an increased abundance of Ruminococcaceae Ruminococcus and Erysipelotrichaceae Erysipelatoclostridium, and a decreased abundance of Coriobacteriaceae Collinsella and Enterobacteriaceae Shigella for both the luminal and mucosal communities. Total SCFA levels were significantly higher, primarily due to an increase in acetic and 2-methylbutanoic acids. Lowering pH decreased luminal community evenness and decreased mucosal community evenness and richness. This corresponded with an increased abundance of Lachnospiraceae Enterocloster, Veillonellaceae Megasphaera, Veillonellaceae Sporomusa, Erysipelotrichaceae Eubacterium, and Alcaligenaceae Sutterella, and decreased abundance of Odoribacteraceae Butyricimonas, Fusobacteriaceae Fusobacterium, Veillonellaceae Phascolarctobacterium, and multiple Enterobacteriaceae species for both the luminal and mucosal communities. Total SCFA levels were significantly lower, with an observed drop in acetic and propionic acids, and increased butyric and valeric acids. Taken together, these results indicate that alterations to environmental pH can modulate the gut microbiota community structure and function, and some changes may occur in a donor-independent manner.

Modulation effects of danshen-honghua herb pair on gut microbiota of acute myocardial ischemia model rat.

In the recent years, a growing number of studies have shown that the occurrence of myocardial ischemia (MI) is closely related to the gut microbiota (GM). The Danshen-Honghua herb pair (DHHP), a classic combination in traditional Chinese herbal formulas, has been widely applied throughout history to cure cardiovascular disease, exhibiting remarkable clinical efficacy to treat ischemic heart disease (IHD). However, the intrinsic regulation mechanism of DHHP in treating MI remains unclear. This study aims to investigate the possible protective mechanism of DHHP in rats with acute myocardial ischemia (AMI) induced by isoproterenol (ISO) through 16S rRNA gene sequencing technique. Pharmacodynamic results showed that DHHP significantly ameliorated the pathological changes and improved the abnormal cardiac enzymes levels in the AMI rats. In addition, GM analysis demonstrated that DHHP effectively ameliorated the ISO-induced dysbiosis of the GM community, mainly by enhancing the GM diversity and increasing the relative abundance of Bacteroides, Roseburia, unclassified_f__Lachnospiraceae, and Lachnospiraceae_NK4A136_group, the abundance ratio of Bacteroidetes to Firmicutes, and decreasing the relative abundance of Escherichia-Shigella and Enterococcus. In summary, this study revealed that DHHP could improve ischemic myocardial injury in rats, and that its regulation mechanism is associated with significantly ameliorating the composition of GM, thus contributing to further our understanding of the anti-MI mechanisms of DHHP.

Histamine Causes Pyroptosis of Liver by Regulating Gut-Liver Axis in Mice.

Huangjiu usually caused rapid-drunkenness and components such as β-benzyl ethanol (β-be), isopentanol (Iso), histamine (His), and phenethylamine (PEA) have been reported linked with intoxication. However, the destructive effect of these components on gut microbiota and liver is unclear. In this study, we found oral treatment of these components, especially His, stimulated the level of oxidative stress and inflammatory cytokines in liver and serum of mice. The gut microbiota community was changed and the level of lipopolysaccharide (LPS) increased significantly. Additionally, cellular pyroptosis pathway has been assessed and correlation analysis revealed a possible relationship between gut microbiota and liver pyroptosis. We speculated oral His treatment caused the reprogramming of gut microbiota metabolism, and increased LPS modulated the gut-liver interaction, resulting in liver pyroptosis, which might cause health risks. This study provided a theoretical basis for the effect of Huangjiu, facilitating the development of therapeutic and preventive strategies for related inflammatory disorders.

Distinct Diet-Microbiota-Metabolism Interactions in Overweight and Obese Pregnant Women: a Metagenomics Approach

ABSTRACTDiet and gut microbiota are known to modulate metabolic health. Our aim was to apply a metagenomics approach to investigate whether the diet-gut microbiota-metabolism and inflammation relationships differ in pregnant overweight and obese women. This cross-sectional study was conducted in overweight (n = 234) and obese (n = 152) women during early pregnancy. Dietary quality was measured by a validated index of diet quality (IDQ). Gut microbiota taxonomic composition and species diversity were assessed by metagenomic profiling (Illumina HiSeq platform). Markers for glucose metabolism (glucose, insulin) and low-grade inflammation (high sensitivity C-reactive protein [hsCRP], glycoprotein acetylation [GlycA]) were analyzed from blood samples. Higher IDQ scores were positively associated with a higher gut microbiota species diversity (r = 0.273, P = 0.007) in obese women, but not in overweight women. Community composition (beta diversity) was associated with the GlycA level in the overweight women (P = 0.04) but not in the obese. Further analysis at the species level revealed a positive association between the abundance of species Alistipes finegoldii and the GlycA level in overweight women (logfold change = 4.74, P = 0.04). This study has been registered at ClinicalTrials.gov under registration no. NCT01922791 (https://clinicaltrials.gov/ct2/show/NCT01922791).IMPORTANCE We observed partially distinct diet-gut microbiota-metabolism and inflammation responses in overweight and obese pregnant women. In overweight women, gut microbiota community composition and the relative abundance of A. finegoldii were associated with an inflammatory status. In obese women, a higher dietary quality was related to a higher gut microbiota diversity and a healthy inflammatory status.

Structural Characteristics of Inulin and Microcrystalline Cellulose and Their Effect on Ameliorating Colitis and Altering Colonic Microbiota in Dextran Sodium Sulfate-Induced Colitic Mice.

Several studies have reported that dietary fibers (DFs) from plants may exert beneficial effects on inflammatory bowel disease. In the present study, we investigated the structural differences of soluble DF (inulin) and insoluble DF (microcrystalline cellulose, MCC) and their effects on the intestinal barrier integrity, gut microbiota community, and inflammation response in mice with dextran sodium sulfate (DSS)-induced colitis. Mice were fed for 21 days with diets containing inulin or MCC (2.5 g/kg body weight), and colitis was induced by administration of DSS (4% w/v) in drinking water during the last 8 days of experimentation. The results showed that inulin and MCC differ in morphology and structure. MCC exhibited a smaller particle size, a larger specific surface area, and higher thermal stability than inulin. In addition, both inulin and MCC restored various physical signs (body weight, colon weight and length, disease activity index score, and infiltration of inflammatory cells), gut barrier function (as evidenced by the increased expression of claudin-3, claudin-7, ZO-2, occludin, JAM-2, and MUC-3 and the decreased activity of myeloperoxidase activity), downregulation of mRNA expression of proinflammatory cytokines (caspase-1, NLPR3, TLR4, TNF-α, and IL-1β), and modulation of colon microbiota community. Taken together, the present study demonstrates that DFs differ in morphology and structure and ameliorate DSS-induced colitis in mice by blocking proinflammatory cytokines, reinforcing gut barrier integrity, and modulating gut microbiota. Therefore, DFs, especially inulin, are promising dietary supplements to alleviate intestinal inflammation.