Altered Gut Microbiota Composition Research Articles

Dietary cholesterol drives the development of nonalcoholic steatohepatitis by altering gut microbiota mediated bile acid metabolism in high-fat diet fed mice

Nonalcoholic fatty liver disease (NAFLD) is the most widespread chronic liver disorder globally. Unraveling the pathogenesis of simple fatty liver to nonalcoholic steatohepatitis (NASH) has important clinical significance for improving the prognosis of NAFLD. Here, we explored the role of a high-fat diet alone or combined with high cholesterol in causing NASH progression. Our results demonstrated that high dietary cholesterol intakes accelerate the progression of spontaneous NAFLD and induces liver inflammation in mice. An elevation of hydrophobic unconjugated bile acids cholic acid (CA), deoxycholic acid (DCA), muricholic acid and chenodeoxycholic acid, was observed in high-fat and high-cholesterol diet fed mice. Full-length sequencing of the 16S rDNA gene of gut microbiota revealed a significant increase in the abundance of Bacteroides, Clostridium, and Lactobacillus that possess bile salt hydrolase activity. Furthermore, the relative abundance of these bacterial species was positively correlated with content of unconjugated bile acids in liver. Moreover, the expression of genes related to bile acid reabsorption (organic anion-transporting polypeptides, Na+-taurocholic acid cotransporting polypeptide, apical sodium dependent bile acid transporter and organic solute transporter β) was found to be increased in mice with a high-cholesterol diet. Lastly, we observed that hydrophobic bile acids CA and DCA induce an inflammatory response in free fatty acids-induced steatotic HepG2 cells. In conclusion, high dietary cholesterol promotes the development of NASH by altering gut microbiota composition and abundance and thereby influencing with bile acid metabolism.

Gut Microbiota Dysbiosis and Increased NLRP3 Levels in Patients with Pregnancy-Induced Hypertension

Pregnancy-induced hypertension (PIH) is one of the most common diseases, causing high maternal morbidity and mortality. However, the correlation of gut microbiota in PIH has not been reported. Our aim was to characterize the intestinal microbiota of patients with PIH compared with healthy people. We analyzed and compared the gut microbiota communities in the feces of 28 PIH patients with pregnancy(not pre-pregnancy) body mass index (including height and weight)-matched healthy controls using 16S rRNA gene sequencing and then investigate the relationships among gut microbiota, cytokines, and PIH. Compared with the healthy group, microbial α diversity was lower in the PIH group, but not statistically significant different. At the phylum level, Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria exhibited obvious differences between the PIH and control groups. LEfSe analysis found 33 differentially abundant taxa between the two groups. The production of pro-inflammatory cytokines in PIH serum or placenta tissues was higher than that of the control group. In addition to alterations in gut microbiota composition, we also found that the Bac_Prevotellaceae, Pre_Prevotella bacteria were positively correlated with NLRP3 level, but negatively correlated with Bac_Bacteroidaceae, Bac_Bacteroides. PIH patients had gut microbiota dysbiosis and increased NLRP3 levels, which will lead to a better understanding of the relationship between the gut microbiota and PIH.

Trimethylamine N-Oxide as a Potential Risk Factor for Non-communicable Diseases: A Systematic Review.

Trimethylamine N-Oxide (TMAO), as a gut microbiota-derived metabolite, has been associated with a number of chronic diseases like cardiovascular diseases. Considering the increasing prevalence of non-communicable diseases (NCDs), we conducted a systematic review to discuss the TMAO association with NCDs. A comprehensive search has been conducted on PubMed, Web of Science, and Scopus databases up to December, 2020. The inclusion criteria were all related observational studies that surveyed the association between TMAO levels and non-communicable diseases. Interventional studies, animal experiments, reviews, case reports, letters, congress abstracts, and studies that were not published in English were excluded. Moreover, related review studies were separately discussed. Within 2191 recorded studies, 99 cross-sectional, case-control and cohort studies met the inclusion criteria. The most common diseases associated with TMAO levels are cardiovascular diseases, diabetes, kidney disease, stroke, inflammatory diseases, neurological disorders, and cancer. Elevated TMAO levels as a consequence of alteration in gut microbiota composition and dietary intake can lead to the incidence of NCDs. The high levels of TMAO can disrupt the homeostasis of glucose and lipids and induce inflammation that leads to serious NCDs. There is a dose-response relationship between TMAO levels and NCDs progression. Therefore, it can be studied as a therapeutic target or prognostic biomarker for dealing with NCDs.

Bamboo Shoots Modulate Gut Microbiota, Eliminate Obesity in High-Fat-Diet-Fed Mice and Improve Lipid Metabolism

Bamboo shoots (BS) have a variety of nutritional benefits; however, their anti-obesity effect and its underlying mechanism of action are still unclear. In this study, we investigated the protective effect of BS against high-fat diet (HFD)-induced gut dysbiosis in mice. After 12 weeks of feeding C57BL/6J mice either on a normal or an HFD with or without BS, metabolic indicators, including blood lipids and glucose tolerance, were measured. 16S rRNA gene sequencing and metabolomics were used to identify alterations in gut microbiota composition and fecal metabolic profiling. The results demonstrated that BS supplementation reduced body weight by 30.56%, mitigated liver damage, and improved insulin resistance and inflammation in obese mice. In addition, BS increased short-chain fatty acid (SCFA) levels and SCFA-producing bacteria (e.g., Lachnospiraceae_NK4A136_group and Norank_f_Muribaculaceae), and reduced levels of harmful bacteria (e.g., Blautia and Burkholderia-Paraburkholderia). Finally, BS increased many beneficial fecal metabolites, such as fatty acids and bile acids, which are highly relevant to the altered gut microbiota. Based on the modulatory effect of BS on microbiota composition and gut metabolite levels observed in this study, we suggest that BS may be beneficial in treating obesity and its related complications.

Metagenomic and targeted metabolomic analyses reveal distinct phenotypes of the gut microbiota in patients with colorectal cancer and type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is an independent risk factor for colorectal cancer (CRC), and the patients with CRC and T2DM have worse survival. The human gut microbiota (GM) is linked to the development of CRC and T2DM, respectively. However, the GM characteristics in patients with CRC and T2DM remain unclear. We performed fecal metagenomic and targeted metabolomics studies on 36 samples from CRC patients with T2DM (DCRC group, n = 12), CRC patients without diabetes (CRC group, n = 12), and healthy controls (Health group, n = 12). We analyzed the fecal microbiomes, characterized the composition and function based on the metagenomics of DCRC patients, and detected the short-chain fatty acids (SCFAs) and bile acids (BAs) levels in all fecal samples. Finally, we performed a correlation analysis of the differential bacteria and metabolites between different groups. Compared with the CRC group, LefSe analysis showed that there is a specific GM community in DCRC group, including an increased abundance of Eggerthella , Hungatella , Peptostreptococcus , and Parvimonas , and decreased Butyricicoccus , Lactobacillus , and Paraprevotella . The metabolomics analysis results revealed that the butyric acid level was lower but the deoxycholic acid and 12-keto-lithocholic acid levels were higher in the DCRC group than other groups ( P < 0.05). The correlation analysis showed that the dominant bacterial abundance in the DCRC group ( Parvimonas , Desulfurispora , Sebaldella , and Veillonellales , among others) was negatively correlated with butyric acid, hyodeoxycholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, chenodeoxycholic acid, cholic acid and glycocholate. However, the abundance of mostly inferior bacteria was positively correlated with these metabolic acid levels, including Faecalibacterium , Thermococci , and Cellulophaga . Unique fecal microbiome signatures exist in CRC patients with T2DM compared to those with non-diabetic CRC. Alterations in GM composition and SCFAs and secondary BAs levels may promote CRC development.

Fecal Immunoglobulin Levels as a Modifier of the Gut Microbiome in Patients with Common Variable Immunodeficiency

ObjectiveCommon variable immunodeficiency (CVID) is the most common clinically relevant entity of inborn errors of immunity. In these patients, an altered gut microbiome composition with reduced diversity has been described. We sought to investigate the fecal immunoglobulin levels and their impact on the gut microflora in patients with CVID.MethodsWe analyzed the gut microbiome of 28 CVID patients and 42 healthy donors (HDs), including 21 healthy household controls, by sequencing the V3 and V4 regions of the bacterial 16S rRNA gene extracted from stool samples. The fecal levels of immunoglobulin A, M, and G of 27 CVID patients and 41 HDs were measured in the supernatant by ELISA and normalized for protein concentration.ResultsWe measured decreased IgA and increased IgG in stool samples from CVID patients compared to HDs. Decreased levels of fecal IgA and IgM were associated with reduced microbial diversity and increased dysbiosis. We identified a large number of significantly differentially abundant taxa, especially in patients with decreased IgA levels, but also in patients with decreased IgM levels compared to their counterparts.ConclusionsCVID patients have an altered gut microbiota composition, which is most prevalent in patients with decreased fecal IgA and IgM levels. In this study, we identify fecal immunoglobulins as a potential modifier of the gut microbiome in CVID patients.

Molecular Pathways of Carcinogenesis in Familial Adenomatous Polyposis.

Familial adenomatous polyposis (FAP) is a genetic syndrome characterized by the presence of multiple polyps in the gastrointestinal tract and a wide range of systemic extra-intestinal manifestations. Patients affected will inevitably undergo abdominal surgery due to the malignant transformation of one or more adenomas. The pathogenesis of the disease is based on a loss of function mutation in adenomatous polyposis coli (APC), a tumor-suppressor gene, inherited following a Mendelian pattern. This gene is a key component of multiple cell functions that cooperate for homeostasis; when mutated, it contributes to the progression of colorectal adenoma into cancer. Recent studies have demonstrated that several additional mechanisms may influence this process, such as alterations in gut microbiota composition and mucosal barrier immunity, interaction with the immune microenvironment and inflammation, the hormone estrogen, and other signaling pathways. These factors represent promising targets of future therapies and chemoprevention, aiming to alter the progressive nature of the disease and improve the quality of life of families affected. Therefore, we performed a narrative review about the current knowledge of the aforementioned pathways involved in colorectal cancer pathogenesis in FAP, exploring the genetic and environmental factors that may contribute to the development of CRC in FAP.

Effect of Probiotic Supplementation on Gut Microbiota in Patients with Major Depressive Disorders: A Systematic Review

There is accumulating evidence on the beneficial effects of probiotic supplementation for patients with depressive disorders. However, prior reviews on the topic have largely focused on clinical effectiveness with limited emphasis on the underlying mechanisms of action and effects of probiotics on gut microbiota. In accordance with PRISMA guidelines, a systematic literature search of Medline, EMBASE and the Cochrane Library using combinations of the key words, ("depress*" OR "MDD" OR "suicide"), ("probiotic" OR "Lactobacillus" OR "Bifidobacterium") AND ("gut" OR "gut micr*" OR "microbiota"), as well as grey literature was performed. We found seven clinical trials involving patients with major depressive disorder (MDD). The small number of studies and heterogeneous sources of data precluded meta-analysis. Most trials (other than one open-label trial) had a low-to-moderate risk of bias, which was largely due to a lack of control for the effects of diet on gut microbiota. Probiotic supplementation yielded only modest effects on depressive symptoms and there were no consistent effects on gut microbiota diversity, and in most instances, no significant alterations in gut microbiota composition were observed after four to eight weeks of probiotic intervention. There is also a lack of systematic reporting on adverse events and no good longer-term data. Patients with MDD may require a longer time to show clinical improvement and the microbial host environment may also need longer than eight weeks to produce significant microbiota alterations. To advance this field, further larger-scale and longer-term studies are required.

IL-22 alters gut microbiota composition and function to increase aryl hydrocarbon receptor activity in mice and humans

BackgroundIL-22 is induced by aryl hydrocarbon receptor (AhR) signaling and plays a critical role in gastrointestinal barrier function through effects on antimicrobial protein production, mucus secretion, and epithelial cell differentiation and proliferation, giving it the potential to modulate the microbiome through these direct and indirect effects. Furthermore, the microbiome can in turn influence IL-22 production through the synthesis of L-tryptophan (L-Trp)-derived AhR ligands, creating the prospect of a host-microbiome feedback loop. We evaluated the impact IL-22 may have on the gut microbiome and its ability to activate host AhR signaling by observing changes in gut microbiome composition, function, and AhR ligand production following exogenous IL-22 treatment in both mice and humans.ResultsMicrobiome alterations were observed across the gastrointestinal tract of IL-22-treated mice, accompanied by an increased microbial functional capacity for L-Trp metabolism. Bacterially derived indole derivatives were increased in stool from IL-22-treated mice and correlated with increased fecal AhR activity. In humans, reduced fecal concentrations of indole derivatives in ulcerative colitis (UC) patients compared to healthy volunteers were accompanied by a trend towards reduced fecal AhR activity. Following exogenous IL-22 treatment in UC patients, both fecal AhR activity and concentrations of indole derivatives increased over time compared to placebo-treated UC patients.ConclusionsOverall, our findings indicate IL-22 shapes gut microbiome composition and function, which leads to increased AhR signaling and suggests exogenous IL-22 modulation of the microbiome may have functional significance in a disease setting.Cw21cUiGabCHLYfc9EL5iqVideo

Evidence for a Causal Role for Escherichia coli Strains Identified as Adherent-Invasive (AIEC) in Intestinal Inflammation.

Enrichment of adherent-invasive Escherichia coli (AIEC) has been consistently detected in subsets of inflammatory bowel disease (IBD) patients. Although some AIEC strains cause colitis in animal models, these studies did not systematically compare AIEC with non-AIEC strains, and causal links between AIEC and disease are still disputed. Specifically, it remains unclear whether AIEC shows enhanced pathogenicity compared to that of commensal E. coli found in the same ecological microhabitat and if the in vitro phenotypes used to classify strains as AIEC are pathologically relevant. Here, we utilized in vitro phenotyping and a murine model of intestinal inflammation to systematically compare strains identified as AIEC with those identified as non-AIEC and relate AIEC phenotypes to pathogenicity. Strains identified as AIEC caused, on average, more severe intestinal inflammation. Intracellular survival/replication phenotypes routinely used to classify AIEC positively correlated with disease, while adherence to epithelial cells and tumor necrosis factor alpha production by macrophages did not. This knowledge was then applied to design and test a strategy to prevent inflammation by selecting E. coli strains that adhered to epithelial cells but poorly survived/replicated intracellularly. Two E. coli strains that ameliorated AIEC-mediated disease were subsequently identified. In summary, our results show a relationship between intracellular survival/replication in E. coli and pathology in murine colitis, suggesting that strains possessing these phenotypes might not only become enriched in human IBD but also contribute to disease. We provide new evidence that specific AIEC phenotypes are pathologically relevant and proof of principle that such mechanistic information can be therapeutically exploited to alleviate intestinal inflammation. IMPORTANCE Inflammatory bowel disease (IBD) is associated with an altered gut microbiota composition, including expansion of Proteobacteria. Many species in this phylum are thought to contribute to disease under certain conditions, including adherent-invasive Escherichia coli (AIEC) strains, which are enriched in some patients. However, whether this bloom contributes to disease or is just a response to IBD-associated physiological changes is unknown. Although assigning causality is challenging, appropriate animal models can test the hypothesis that AIEC strains have an enhanced ability to cause colitis in comparison to other gut commensal E. coli strains and to identify bacterial traits contributing to virulence. We observed that AIEC strains are generally more pathogenic than commensal E. coli and that bacterial intracellular survival/replication phenotypes contributed to disease. We also found that E. coli strains lacking primary virulence traits can prevent inflammation. Our findings provide critical information on E. coli pathogenicity that may inform development of IBD diagnostic tools and therapies.

Periodontitis salivary microbiota exacerbates nonalcoholic fatty liver disease in high-fat diet-induced obese mice

Periodontitis may aggravate the development of nonalcoholic fatty liver disease (NAFLD); however, the precise mechanism is unknown. In this study, salivary microbiota collected from patients with periodontitis was transferred intragastrically to obese mice induced by high-fat diet. Microbiomics and metabolomics analysis were performed to assess the influence of periodontitis salivary microbiota on gut microbiome and liver metabolism. Periodontitis salivary microbiota altered gut microbiota composition and exacerbated intestinal barrier dysfunction in obese mice. Subsequently, the bacterial lipopolysaccharide transported to liver may activate the toll-like receptor 4 signaling and cause the release of pro-inflammatory factors. Moreover, the tryptophan-kynurenine-AhR signal axis was upregulated in liver, which may be related to aggravated hepatic steatosis and glucolipid metabolism dysregulation during NAFLD development. This study indicated that in the context of obesity, periodontitis salivary microbiota may aggravate the pathological progression of NAFLD, in which the tryptophan-AhR pathway may play a key role.

The interaction between dietary fiber and gut microbiota, and its effect on pig intestinal health.

Intestinal health is closely associated with overall animal health and performance and, consequently, influences the production efficiency and profit in feed and animal production systems. The gastrointestinal tract (GIT) is the main site of the nutrient digestive process and the largest immune organ in the host, and the gut microbiota colonizing the GIT plays a key role in maintaining intestinal health. Dietary fiber (DF) is a key factor in maintaining normal intestinal function. The biological functioning of DF is mainly achieved by microbial fermentation, which occurs mainly in the distal small and large intestine. Short-chain fatty acids (SCFAs), the main class of microbial fermentation metabolites, are the main energy supply for intestinal cells. SCFAs help to maintain normal intestinal function, induce immunomodulatory effects to prevent inflammation and microbial infection, and are vital for the maintenance of homeostasis. Moreover, because of its distinct characteristics (e.g. solubility), DF is able to alter the composition of the gut microbiota. Therefore, understanding the role that DF plays in modulating gut microbiota, and how it influences intestinal health, is essential. This review gives an overview of DF and its microbial fermentation process, and investigates the effect of DF on the alteration of gut microbiota composition in pigs. The effects of interaction between DF and the gut microbiota, particularly as they relate to SCFA production, on intestinal health are also illustrated.

The diet rapidly and differentially affects the gut microbiota and host lipid mediators in a healthy population

BackgroundBioactive lipids produced by human cells or by the gut microbiota might play an important role in health and disease. Dietary intakes are key determinants of the gut microbiota, its production of short-chain (SCFAs) and branched-chain fatty acids (BCFAs), and of the host endocannabinoidome signalling, which are all involved in metabolic diseases. This hypothesis-driven longitudinal fixed sequence nutritional study, realized in healthy participants, was designed to determine if a lead-in diet affects the host response to a short-term dietary intervention. Participants received a Mediterranean diet (MedDiet) for 3 days, a 13-day lead-in controlled diet reflecting the average Canadian dietary intake (CanDiet), and once again a MedDiet for 3 consecutive days. Fecal and blood samples were collected at the end of each dietary phase to evaluate alterations in gut microbiota composition and plasma levels of endocannabinoidome mediators, SCFAs, and BCFAs.ResultsWe observed an immediate and reversible modulation of plasma endocannabinoidome mediators, BCFAs, and some SCFAs in response to both diets. BCFAs were more strongly reduced by the MedDiet when the latter was preceded by the lead-in CanDiet. The gut microbiota response was also immediate, but not all changes due to the CanDiet were reversible following a short dietary MedDiet intervention. Higher initial microbiome diversity was associated with reduced microbiota modulation after short-term dietary interventions. We also observed that BCFAs and 2-monoacylglycerols had many, but distinct, correlations with gut microbiota composition. Several taxa modulated by dietary intervention were previously associated to metabolic disorders, warranting the need to control for recent diet in observational association studies.ConclusionsOur results indicate that lipid mediators involved in the communication between the gut microbiota and host metabolism exhibit a rapid response to dietary changes, which is also the case for some, but not all, microbiome taxa. The lead-in diet influenced the gut microbiome and BCFA, but not the endocannabinoidome, response to the MedDiet. A higher initial microbiome diversity favored the stability of the gut microbiota in response to dietary changes. This study highlights the importance of considering the previous diet in studies relating the gut microbiome with lipid signals involved in host metabolism.91qzVqRa16ptEbbFa4LH5iVideo

Altered Gut Microbiota Composition and Its Potential Association in Patients with Advanced Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the second-most-common cause of cancer death. In recent years, studies have suggested that intestinal microbiota dysregulation is closely related to HCC and can affect the therapeutic efficacy of immune checkpoint inhibitors. However, there are few data on the relationship between altered gut microbiota composition and its potential association in patients with advanced hepatocellular carcinoma. Hence, in this study, we aimed to investigate the gut microbiota profile associated with advanced hepatocarcinoma. In total, 20 patients with advanced hepatocarcinoma and 20 matched healthy participants were recruited. Stool samples were collected for 16S rRNA sequencing to confirm intestinal microbiota dysbiosis. The results showed that the Nseqs index in advanced hepatocarcinoma patients was significantly different compared with that in healthy individuals, while the butyrate-producing bacteria decreased and LPS-producing bacteria increased. Meanwhile, Lactobacillus, Anaerostipes, Fusicatenibacter, Bifidobacterium, and Faecalibacterium were significantly correlated with AFP, ALT, AST, and PIVKA. Our findings characterized the gut microbiota composition of advanced hepatocarcinoma, providing an experimental basis and theoretical support for using microbiota to regulate immunotherapy, achieve potential biomarkers for diagnosis, and improve the effect of clinical treatment for patients with advanced hepatocarcinoma.

DOP03 Unfermented β-fructan fibres can induce gut inflammation and tumorigenesis in select Inflammatory Bowel Disease patients mediated by gut microbiota

Abstract Background Dietary fibres are not digested in the bowel; they are fermented by microbes, typically promoting gut health. However, IBD patients have altered gut microbiota composition and can experience sensitivity to consumption of fibres. Our previous findings offered the first mechanistic evidence that if dietary β-fructans (inulin and oligofructose) are not fermented by gut microbes in IBD patients, these fibres can induce inflammation. This diet-induced inflammation could have serious repercussions as chronic inflammation creates a mutagenic environment that promotes progression to colorectal cancer (CRC). We hypothesized that unfermented β-fructans cause tumorigenesis and promotion of IBD progression to CRC. Methods We examined pathways associated with response to β-fructan in a randomized controlled trial examining β-fructan supplementation (15g/day) in UC patients in remission (RNA sequencing). We validated pathways of interest in IBD patient colonic biopsies cultured ex vivo with β-fructans (targeted proteomics and mesoscale discovery). We examined structural changes (microscopy; e.g., tumorigenic architecture) in these biopsies. Further, cell invasion, migration, and proliferation were examined using scratch wound assays and chick chorioallantoic membrane assays (CAM; n=10 embryos per treatment). Results CRC-related pathways (SLIT2/MAPK and SOS1) were induced and anti-tumour gene RPS27A was reduced only in biopsies from remission UC patients who entered relapse following consumption of β-fructans (endpoint versus baseline), not those in the placebo arm who relapsed. Pathways were validated in IBD patient colonic biopsies cultured ex vivo demonstrating oligofructose produced more significant effects than inulin; response correlated with disease severity. Inulin and oligofructose further influenced the processes of migration and invasion reflective of the tumorigenic process of epithelial to mesenchymal transition and risk of CRC. Conclusion Our findings suggest that intolerance and avoidance of fibres in select IBD patients occurs specifically in patients whose gut microbiota do not support fermentation of dietary fibres resulting in increased presence of unfermented dietary fibres in the gut. Here we show that these β-fructan fibres commonly touted as beneficial prebiotics can elicit gut inflammation and tumorigenesis in this subset of IBD patients, suggesting consumption of these fibres should be avoided in these patients.

Alterations in Gut Microbiota Composition in Patients with COVID-19: A Pilot Study of Whole Hypervariable 16S rRNA Gene Sequencing.

It is crucial to consider the importance of the microbiome and the gut-lung axis in the context of SARS-CoV-2 infection. This pilot study examined the fecal microbial composition of patients with COVID-19 following a 3-month recovery. Using for the first time metagenomic analysis based on all hypervariable regions (V1-V9) of the 16S rRNA gene, we have identified 561 microbial species; however, 17 were specific only for the COVID-19 group (n = 8). The patients' cohorts revealed significantly greater alpha diversity of the gut microbiota compared to healthy controls (n = 14). This finding has been demonstrated by operational taxonomic units (OTUs) richness (p < 0.001) and Chao1 index (p < 0.01). The abundance of the phylum Verrucomicrobia was 30 times higher in COVID-19 patients compared to healthy subjects. Accordingly, this disproportion was also noted at other taxonomic levels: in the class Verrucomicrobiae, the family Verrucomicrobiaceae, and the genus Akkermansia. Elevated pathobionts such as Escherichia coli, Bilophila wadsworthia, and Parabacteroides distasonis were found in COVID-19 patients. Considering the gut microbiota's ability to disturb the immune response, our findings suggest the importance of the enteric microbiota in the course of SARS-CoV-2 infection. This pilot study shows that the composition of the microbial community may not be fully restored in individuals with SARS-CoV-2 following a 3-month recovery.

Serum Vitamin D Level and Gut Microbiota in Women.

Obesity and vitamin D deficiency are two major public health concerns. Evidence suggests that alteration in gut microbiota composition is a possible risk factor for obesity. Additionally, altered vitamin D status has a potential role in shaping the gut microbial community. Further, the prevalence of obesity has been rising in the Middle East, especially among women of reproductive age, which is of specific concern due to its adverse effects on the health of their offspring. To date, limited evidence is available on the association between gut microbiota composition and vitamin D levels in Arab women. This study aims to identify the associations between serum vitamin D, gut microbiota, and obesity among Saudi females. The current study is a case-control study including 92 women aged 18 to 25 years, (n = 48) with normal weight and (n = 44) with obesity. Anthropometric, biochemical, lifestyle data, and fecal samples were collected and analyzed. We used shotgun metagenomic sequencing to characterize microbial communities of stool samples. Vitamin D levels were significantly associated with alpha and beta diversities. Serum vitamin D levels were positively associated with bacteria known to regulate immunological responses; Bacteroides thetaiotaomicron in the normal weight group (r = 0.34, p = 0.03) and Bifidobacterium adolescentis in the obesity group (r = 0.33, p = 0.04). In conclusion, the findings suggest that vitamin D status may play a role in regulating the gut microbiota composition by inhibiting the growth of pathogenic bacteria while nourishing the beneficial strains.

STING Promotes Intestinal IgA Production by Regulating Acetate-producing Bacteria to Maintain Host-microbiota Mutualism.

Intestinal Immunoglobulin A (IgA) is crucial in maintaining host-microbiota mutualism and gut homeostasis. It has been shown that many species of gut bacteria produce cyclic dinucleotides, along with an abundance of microbiota-derived DNA present within the intestinal lumen, which triggers the tonic activation of the cytosolic cGAS-STING pathway. However, the role of STING in intestinal IgA remains poorly understood. We further investigated whether and how STING affects intestinal IgA response. Intestinal IgA was determined between wild-type (WT) mice and Sting-/- mice in steady conditions and upon enteric Citrobacter rodentium infection. STING agonists were used to stimulating B cells or dendritic cells in vitro. Gut microbiota composition was examined by 16S ribosomal RNA gene sequencing. Bacteria metabolomics functional analyses was performed by PICRUSt2. Fecal short-chain fatty acid (SCFA) was determined by Mass spectrometry and Cedex Bio Analyzer. Gut bacteria from WT mice and Sting-/- mice were transferred into germ-free mice and antibiotic-pretreated mice. Intestinal IgA response was impaired in Sting-/- mice. However, STING agonists did not directly stimulate B cells or dendritic cells to induce IgA. Interestingly, Sting-/- mice displayed altered gut microbiota composition with decreased SCFA-producing bacteria and downregulated SCFA fermentation pathways. Transfer of fecal bacteria from Sting-/- mice induced less IgA than that from WT mice in germ-free mice and antibiotic-pretreated mice, which is mediated by GPR43. Acetate, the dominant SCFA, was decreased in Sting-/- mice, and supplementation of acetate restored intestinal IgA production in Sting-/- mice. STING promotes intestinal IgA by regulating acetate-producing gut bacteria.

The Implication of Mechanistic Approaches and the Role of the Microbiome in Polycystic Ovary Syndrome (PCOS): A Review.

As a complex endocrine and metabolic condition, polycystic ovarian syndrome (PCOS) affects women's reproductive health. These common symptoms include hirsutism, hyperandrogenism, ovulatory dysfunction, irregular menstruation, and infertility. No one knows what causes it or how to stop it yet. Alterations in gut microbiota composition and disruptions in secondary bile acid production appear to play a causative role in developing PCOS. PCOS pathophysiology and phenotypes are tightly related to both enteric and vaginal bacteria. Patients with PCOS exhibit changed microbiome compositions and decreased microbial diversity. Intestinal microorganisms also alter PCOS patient phenotypes by upregulating or downregulating hormone release, gut-brain mediators, and metabolite synthesis. The human body's gut microbiota, also known as the "second genome," can interact with the environment to improve metabolic and immunological function. Inflammation is connected to PCOS and may be caused by dysbiosis in the gut microbiome. This review sheds light on the recently discovered connections between gut microbiota and insulin resistance (IR) and the potential mechanisms of PCOS. This study also describes metabolomic studies to obtain a clear view of PCOS and ways to tackle it.

Altered gut microbiota composition in children and their caregivers infected with the SARS-CoV-2 Omicron variant.

Gut microbiota alterations have been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19). This study aimed to explore gut microbiota changes in a prospective cohort of COVID-19 children and their asymptomatic caregivers infected with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) Omicron variant. A total of 186 participants, including 59 COVID-19 children, 50 asymptomatic adult caregivers, 52 healthy children (HC), and 25 healthy adults (HA), were recruited between 15 April and 31 May 2022. The gut microbiota composition was determined by 16S rRNA gene sequencing in fecal samples collected from the participants. Gut microbiota functional profiling was performed by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software. The gut microbiota analysis of beta diversity revealed that the fecal microbial community of COVID-19 children remained far distantly related to HC. The relative abundances of the phyla Actinobacteria and Firmicutes were decreased, whereas Bacteroidetes, Proteobacteria, and Verrucomicrobiota were increased in COVID-19 children. Feces from COVID-19 children exhibited notably lower abundances of the genera Blautia, Bifidobacterium, Fusicatenibacter, Streptococcus, and Romboutsia and higher abundances of the genera Prevotella, Lachnoclostridium, Escherichia-Shigella, and Bacteroides than those from HC. The enterotype distributions of COVID-19 children were characterized by a high prevalence of enterotype Bacteroides. Similar changes in gut microbiota compositions were observed in asymptomatic caregivers. Furthermore, the microbial metabolic activities of KEGG (Kyoto Encyclopedia of Genes and Genomes) and COG (cluster of orthologous groups of proteins) pathways were perturbed in feces from subjects infected with the SARS-CoV-2 Omicron variant. Our data reveal altered gut microbiota compositions in both COVID-19 children and their asymptomatic caregivers infected with the SARS-CoV-2 Omicron variant, which further implicates the critical role of gut microbiota in COVID-19 pathogenesis.