Involvement Of Gut Microbiota Research Articles

Nutrition in Spondyloarthritis and Related Immune-Mediated Disorders.

Recent research on the pathogenesis of spondyloarthritis and related immune-mediated diseases associated with human leukocyte antigen class I molecule B27 (HLA-B27) has led to significant progress in terms of management and prognosis, with multiple treatments being constantly evaluated and implemented. Correlations between the genetic background of spondyloarthritis and inflammatory bowel diseases and the inflammatory processes involving gut microbiota have been established. This knowledge has allowed progress in pharmacological therapy. The role of diet in the pathogenesis and treatment of diseases pertaining to the HLA-B27 spectrum is of great significance, considering possible future applications in individualized medicine. Diet impacts the composition of gut microbiota, representing a substrate for the synthesis of metabolites affecting the mucosal immune system. Certain pro-inflammatory mediators, such as emulsifiers and microparticles, induce a more profound cytokine response, promoting inflammation. Numerous diets, including the low-starch diet, the Mediterranean diet, diets with low contents of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (low-FODMAP diets), gluten-free diets and fasting, have been analysed and correlated with patients’ symptomatology and dietary adherence. The aim of this review is to provide an extensive perspective on the diets available to patients with spondyloarthritis and related immune-mediated disorders.

Alteration of Gut Microbiota: New Strategy for Treating Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is defined as a complex heterogeneous disorder and characterized by stereotyped behavior and deficits in communication and social interactions. The emerging microbial knowledge has pointed to a potential link between gut microbiota dysbiosis and ASD. Evidence from animal and human studies showed that shifts in composition and activity of the gut microbiota may causally contribute to the etiopathogenesis of core symptoms in the ASD individuals with gastrointestinal tract disturbances and act on microbiota-gut-brain. In this review, we summarized the characterized gut bacterial composition of ASD and the involvement of gut microbiota and their metabolites in the onset and progression of ASD; the possible underlying mechanisms are also highlighted. Given this correlation, we also provide an overview of the microbial-based therapeutic interventions such as probiotics, antibiotics, fecal microbiota transplantation therapy, and dietary interventions and address their potential benefits on behavioral symptoms of ASD. The precise contribution of altering gut microbiome to treating core symptoms in the ASD needs to be further clarified. It seemed to open up promising avenues to develop microbial-based therapies in ASD.

Active microbial metabolites study on antitussive and expectorant effects and metabolic mechanisms of platycosides fraction of Platycodonis Radix

A new method involving gut microbiota biotransformation, spectrum-effect relationship analysis and metabolomics analysis was developed to study the antitussive and expectorant microbial metabolites of platycosides fraction (MPFs) of Platycodonis Radix. Furthermore, their possible metabolic mechanisms were studied for the first time. The findings showed that the antitussive and expectorant effects of the platycosides fraction (PF) were significantly enhanced by the gut microbiota biotransformation. 11 active antitussive microbial metabolites and 12 active expectorant microbial metabolites, which shared 8 components, were successfully screened out via spectrum-effect relationship analysis. The prototypes of the active microbial metabolites could be reversely traced according to the gut microbiota biotransformation pathways. It was found out that one platycoside could produce several active microbial metabolites and several different platycosides could produce the same active microbial metabolite. In addition, the metabolomics analysis showed that both the PF and its active microbial metabolites could regulate the same metabolomic pathways of Linoleic acid metabolism, Arachidonic acid metabolism and Glycerophospholipid metabolism to exert antitussive activity, and regulate the same metabolomic pathway of Arachidonic acid metabolism to exert expectorant activity. These findings suggested the microbial metabolites may be the active forms of the platycosides. Overall, the proposed approach was useful in screening the active microbial metabolites; this work explained the in vivo antitussive and expectorant metabolic mechanisms of multi-constituents, multi-targets and synergistic effects of PF of Platycodonis Radix.

Recent topics on interorgan communication networks and gut microbiota

The living body is composed of diverse organ systems, each of which has its own characteristic control mechanisms and complex in vivo responses. Between the brain and organs such as the heart, kidney, liver, pancreas, gastrointestinal tract, and even muscles, there is a sophisticated and complex regulatory system. Coordinated interactions through communication between organs are essential for maintaining health. In this review, we introduce four research trends in inter-organ networks, with a focus on the digestive system: 1) Inter-organ networks on metabolic systems, 2) Inter-organ networks originating from the gastrointestinal tract, 3) Intestinal bacteria, that is one of the biggest topics in recent years, 4) Research results on the involvement of gut microbiota in the inter-organ network between the kidney and the gastrointestinal tract. An integrated understanding and investigation of the regulatory mechanisms of inter-organ communication networks are expected to extend healthy life span and improve quality of life.

The interplay between oat beta glucan, gut microbiota and gut-liver axis in treatment of obesity associated non-alcoholic steatohepatitis and Type II diabetes mellitus

Dietary fibers regulate host health through various mechanisms related to their physicochemical structure and physiological properties in the gut. The interplay between diet, gut microbiota and human host appear to play a significant role in pathogenesis of obesity associated complications. This study was designed to unravel oat beta glucan modulatory effect on non-alcoholic steatohepatitis and type II diabetes mellitus in high fat fed rats and to explain possible pathomechanics involving gut microbiota and gut liver axis. Sixty male albino rats were included and randomly divided into four equal groups: control group; positive control group; diet induced obesity group; oat beta glucan treated group. All were subjected to assessment of glycemic profile; liver enzymes; serum trimethylamine-N-oxide levels; hepatic G-protein coupled receptor 43 relative gene expression. Histopathological examination of hepatic tissue was performed. Results revealed that oat beta glucan administration improved the biochemical changes. The histopathological findings confirmed the biochemical changes. Gut microbiota appeared to be highly implicated via its metabolites short chain fatty acids and trimethylamine. Our conclusion was that oat beta glucan was a successful compliance in the management strategy of hepatic steatosis and diabetes mellitus via modulating a number of gut microbial products.

The role of diet in the prevention of migraine attacks

The review provides information concerning the influence of dietary factors and different types of diet on the origin and frequency of migraine headaches according to the up-to-date scientific data. The relevance of the problem is associated with high prevalence of migraine, which is a common cause of disability amongst young people. Gut – brain axis takes a significant place in the pathophysiology of migraine. The concept of a gut-brain axis explains a bidirectional relationship between the gastrointestinal system and the central nervous system. It has been suggested that changes in the gut-brain axis functioning may play a role in the pathogenesis of migraine. The review describes possible mechanisms of gut microbiota involvement in the pathogenesis of migraine. Knowledge of the important role of food triggers in migraine has contributed to the development of a dietary therapeutic strategy for the prevention of migraine headache. The paper contains data concerning possible pathogenetically substantiated effects of various types of diet (elimination, epigenetic, ketogenic) in migraine prevention, given the lack of efficacy and side effects of current migraine drug therapy. The review discusses the possible positive effects of dietary approaches on migraine through their beneficial influence on the intestinal microbiota and functioning of the gut-brain axis. Conclusions. An update on the role of diet in the pathogenesis and prevention of migraine attacks is an extremely important and promising scientific field, which requires further research with the development of personalized approaches taking into account the individual characteristics of each patient.

Interaction of Gut Microbiome and Host microRNAs with the Occurrence of Colorectal and Breast Cancer and Their Impact on Patient Immunity.

Breast and colorectal cancers are two primary malignancies on which most of the research done worldwide investigates the potential genetic and environmental risk factors and thereby tries to develop therapeutic methods to improve prognosis. Breast cancer is the most diagnosed cancer type in women, while colorectal cancer is diagnosed in males as the third most and females as the second most cancer type. Though these two cancer types are predominantly seen in adult patients worldwide, in the current context, these malignancies are diagnosed at a younger age with a significant rate of incidents than previous. Such early-onset cancers are generally present at an advanced stage of the most aggressive type with a poor prognosis. In the past, the focus of the research was mainly on studying possible candidate genes to understand the onset. However, it is now recognized that genetics, epigenetics, and other environmental factors play a pivotal role in cancer susceptibility. Thus, most studies were diversified to study the behavior of host microRNAs, and the involvement of gut microbiota and good communication between them surfaced in the occurrence and state of the disease. It is understood that the impact of these factors affects the outcome of the disease. Out of the adverse outcomes identified relating to the disease, immunosuppression is one of the most concerning outcomes in the current world, where such individuals remain vulnerable to infections. Recent studies revealed that microbiome and microRNA could create a considerable impact on immunosuppression. This review focused on the behavior of host microRNAs and gut microbiome for the onset of the disease and progression, thereby influencing an individual’s immunosuppression. Understanding the interactions among microRNA, microbiome, presentation of the disease, and impact on the immune system will be immensely useful for developing future therapeutic strategies based on targeting host microRNA and the patient’s gut microbiome. Therapies such as inhibitory-miRNA therapies, miRNA mimic-based therapeutics, immune checkpoint blockade therapies, and bacteria‐assisted tumor‐targeted therapies help modulate cancer. At the same time, it paid equal attention to potential noninvasive biomarkers in diagnosis, prognosis, and therapeutics in both cancers.

Cytotoxic T-Cell Trafficking Chemokine Profiles Correlate With Defined Mucosal Microbial Communities in Colorectal Cancer.

The involvement of gut microbiota in T-cell trafficking into tumor tissue of colorectal cancer (CRC) remains to be further elucidated. The current study aimed to evaluate the expression of major cytotoxic T-cell trafficking chemokines (CTTCs) and chemokine-associated microbiota profiles in both tumor and adjacent normal tissues during CRC progression. We analyzed the expression of chemokine C-X-C motif ligands 9, 10, and 11 (CXCL9, CXCL10, and CXCL11), and C-C motif ligand 5 (CCL5), characterized gut mucosa-associated microbiota (MAM), and investigated their correlations in CRC patients. Our results showed that the expression of CXCL9, CXCL10, and CXCL11 was significantly higher in tumor than in adjacent normal tissues in 136 CRC patients. Notably, the high expression of CXCL9 in tumor tissues was associated with enhanced CD8+ T-cell infiltration and improved survival. Moreover, the MAM in tumor tissues showed reduction of microbial diversity and increase of oral bacteria. Microbial network analysis identified differences in microbial composition and structure between tumor and adjacent normal tissues. In addition, stronger associations between oral bacteria and other gut microbes were observed. Furthermore, the correlation analysis between the defined MAM and individual CTTCs showed that the CTTCs’ correlated operational taxonomic units (OTUs) in tumor and adjacent normal tissues rarely overlap with each other. Notably, all the enriched OTUs were positively correlated with the CTTCs in either tumor or adjacent normal tissues. Our findings demonstrated stronger interactions between oral bacteria and gut microbes, and a shifted correlation pattern between MAM and major CTTCs in tumor tissues, underlining possible mechanisms of gut microbiota–host interaction in CRC.

Involvement of Gut Microbiota in Schizophrenia and Treatment Resistance to Antipsychotics.

The gut microbiota is constituted by more than 40,000 bacterial species involved in key processes including high order brain functions. Altered composition of gut microbiota has been implicated in psychiatric disorders and in modulating the efficacy and safety of psychotropic medications. In this work we characterized the composition of the gut microbiota in 38 patients with schizophrenia (SCZ) and 20 healthy controls (HC), and tested if SCZ patients with different response to antipsychotics (18 patients with treatment resistant schizophrenia (TRS), and 20 responders (R)) had specific patterns of gut microbiota composition associated with different response to antipsychotics. Moreover, we also tested if patients treated with typical antipsychotics (n = 20) presented significant differences when compared to patients treated with atypical antipsychotics (n = 31). Our findings showed the presence of distinct composition of gut microbiota in SCZ versus HC, with several bacteria at the different taxonomic levels only present in either one group or the other. Similar findings were observed also depending on treatment response and exposure to diverse classes of antipsychotics. Our results suggest that composition of gut microbiota could constitute a biosignatures of SCZ and TRS.

Nanoparticles and Gut Microbiota in Colorectal Cancer

Recent years have witnessed an unprecedented growth in the research area of nanomedicine. There is an increasing optimism that nanotechnology applied to medicine will bring significant advances in the diagnosis and treatment of various diseases, including colorectal cancer (CRC), a type of neoplasm affecting cells in the colon or the rectum. Recent findings suggest that the role of microbiota is crucial in the development of CRC and its progression. Dysbiosis is a condition that disturbs the normal microbial environment in the gut and is often observed in CRC patients. In order to detect and treat precancerous lesions, new tools such as nanotechnology-based theranostics, provide a promising option for targeted marker detection or therapy for CRC. Because the presence of gut microbiota influences the route of biomarker detection and the route of the interaction of nanoparticle/drug complexes with target cells, the development of nanoparticles with appropriate sizes, morphologies, chemical compositions and concentrations might overcome this fundamental barrier. Metallic particles are good candidates for nanoparticle-induced intestinal dysbiosis, but this aspect has been poorly explored to date. Herein, we focus on reviewing and discussing nanotechnologies with potential applications in CRC through the involvement of gut microbiota and highlight the clinical areas that would benefit from these new medical technologies.

Gut Microbiota in Psychiatric Disorders: A Systematic Review.

This systematic review sought to comprehensively summarize gut microbiota research in psychiatric disorders following PRISMA guidelines. Literature searches were performed on databases using keywords involving gut microbiota and psychiatric disorders. Articles in English with human participants up until February 13, 2020, were reviewed. Risk of bias was assessed using a modified Newcastle-Ottawa Scale for microbiota studies. Sixty-nine of 4231 identified studies met the inclusion criteria for extraction. In most studies, gut microbiota composition differed between individuals with psychiatric disorders and healthy controls; however, limited consistency was observed in the taxonomic profiles. At the genus level, the most replicated findings were higher abundance of Bifidobacterium and lower abundance of Roseburia and Faecalibacterium among patients with psychiatric disorders. Gut bacteria that produce short-chain fatty acids, such as Roseburia and Faecalibacterium, could be less abundant in patients with psychiatric disorders, whereas commensal genera, for example, Bifidobacterium, might be more abundant compared with healthy controls. However, most included studies were hampered by methodological shortcomings including small sample size, unclear diagnostics, failure to address confounding factors, and inadequate bioinformatic processing, which might contribute to inconsistent results. Based on our findings, we provide recommendations to improve quality and comparability of future microbiota studies in psychiatry.

New concepts on immunology of Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory and immune-driven demyelinating disease of the central nervous system (CNS). During the past decade, major advances have been made to understand the development of MS as well as its progressive stage.Here, we discuss some emerging concepts on immunology of MS, including the growing interest in the involvement of gut microbiota and the recent pathological concepts on the progression phase. Finally, we present some immuno-tools recently available that contribute to better understand diversity and function of the immune system.

Modulation of gut microbiota by chondroitin sulfate calcium complex during alleviation of osteoporosis in ovariectomized rats

Although chondroitin sulfate calcium complex (CSCa) was claimed to have the bioactivity for bone care in vitro, its anti-osteoporosis bioactivity was little reported in vivo. Here, the effects of CSCa on osteoporosis rats were investigated. Results showed that, compared with the osteoporosis rats, CSCa could improve the bone mineral density and microstructure of femur, and change the bone turnover markers level in serum. 16S rRNA sequencing and metabolomics analysis indicated CSCa intervention altered the composition of gut microbiota along with metabolite profiles in ovariectomized rat faeces. The correlation analysis showed some gut microbiota taxa were significantly correlated with osteoporosis phenotypes and the enriched metabolites. Taken together, dietary CSCa intervention has the potential to alleviate the osteoporosis and related symptoms probably involving gut microbiota or the metabolite profiles as demonstrated in rats. This study provides some scientific evidence for the potential effects of CSCa as the food supplement on the osteoporosis.

High sucrose diet-induced dysbiosis of gut microbiota promotes fatty liver and hyperlipidemia in rats

Excess sucrose intake has been found to be a major factor in the development of metabolic syndrome, especially in promoting nonalcoholic fatty liver disease. The excess fructose is believed to targets the liver to promote de novo lipogenesis, as described in major biochemistry textbooks. On the contrary, in this study, we explored the possible involvement of gut microbiota in excess sucrose-induced lipid metabolic disorders, to validate a novel mechanism by which excess sucrose causes hepatic lipid metabolic disorders via alterations to the gut microbial community structure. Wistar male rats were fed either a control starch diet or a high-sucrose diet for 4 weeks. Half of the rats in each group were treated with an antibiotic cocktail delivered via drinking water for the entire experimental period. After 4 weeks, rats fed with the high-sucrose diet showed symptoms of fatty liver and hyperlipidemia. The architecture of cecal microbiota was altered in rats fed with high-sucrose diet as compared to the control group, with traits including increased ratios of the phyla Bacteroidetes/Firmicutes, reduced α-diversity, and diurnal oscillations changes. Antibiotic administration rescued high-sucrose diet-induced lipid accumulation in the both blood and liver. Levels of two microbial metabolites, formate and butyrate, were reduced in rats fed with the high-sucrose diet. These volatile short-chain fatty acids might be responsible for the sucrose-induced fatty liver and hyperlipidemia. Our results indicate that changes in the gut microbiota induced by a high-sucrose diet would promote the development of nonalcoholic fatty liver disease via its metabolites, such as short-chain fatty acids.

Goat Milk Improves Glucose Homeostasis via Enhancement of Hepatic and Skeletal Muscle AMP-Activated Protein Kinase Activation and Modulation of Gut Microbiota in Streptozocin-Induced Diabetic Rats.

Previously, the metabolic benefits of goat milk consumption in high-fat diet-fed rats are demonstrated. However, the effects are only reported in one animal model and the involvement of gut microbiota is not investigated. The aim of this study is to investigate the effects of goat milk consumption on glucose homeostasis and gut microbiota in streptozocin (STZ)-induced diabetic rats. STZ-induced diabetic rats are fed with three dosages of goat milk: 2.5, 5, and 10g kg-1 . Parameters related to glucose homeostasis, hepatic and skeletal muscle AMP-activated protein kinase (AMPK) activation, and gut microbiota are investigated. The dose of 10g kg-1 exerts more metabolic benefits. Goat milk consumption improves fasting glucose levels, glucose tolerance, insulin sensitivity, and promotes hepatic and skeletal muscle AMPK activation in STZ-injected diabetic rats. Goat milk modulates gut microbiota, increases the relative abundance of Lactobacillus, and augments levels of propionic and butyric acids. This study demonstrates the metabolic benefits of goat milk consumption in STZ-induced diabetic rats, which is consistent with the previous observations in high-fat diet-induced diabetic rats. Furthermore, this study elucidates the modulation of gut microbiota by goat milk, which likely mediates the metabolic effects of goat milk.

Gentamicin Induced Microbiome Adaptations Associate With Increased BCAA Levels and Enhance Severity of Influenza Infection.

Involvement of gut microbiota in pulmonary disease by the gut-lung axis has been widely observed. However, the cross-talk messengers between respiratory mucosal immunity and gut microbiota are largely unknown. Using selective pharmacologic destruction of gut microenvironment mouse models, we found gut microbiota displayed significantly lower alpha diversity and relative abundance of bacteria in Gentamicin treated mice. Metagenomic studies revealed functional differences in gut bacteria in altering metabolic profiles in mice blood. Branched-chain amino acids (BCAAs) are the essential factors linked between gut and lung. During this process, selective destruction of gut microbiota by Gentamicin induced high levels of BCAAs, and the high levels of BCAAs impacted the lung immunity against influenza virus. In vivo, Gentamicin-treated mice or mice fed with high BCAAs diets displayed reduced survival. At the sites of infection, the number of CD11b+Ly6G+ cells decreased, and CD8+ T cells increased accompanied by exuberant expression of pro-inflammatory cytokines could result in tissue damage. CD11b+Ly6G+ cells transplantation conferred remarkable protection from influenza virus infections. In vitro, BCAAs promoted bone marrow-derived cells differentiation to dendritic cells. Taken together, these findings demonstrate that Gentamicin induced disruption of the gut microbiota leads to increased BCAA levels that suppress CD11b+Ly6c+ cell development in association with overactive CD8+ T responses which may contribute to enhanced severity of the viral infection.

Dietary tryptophan depletion alters the faecal bacterial community structure of compulsive drinker rats in schedule-induced polydipsia

RationaleCompulsive behaviour, present in different psychiatric disorders such as obsessive-compulsive disorder, schizophrenia and drug abuse, is associated with altered levels of serotonin (5-hydroxytryptamine, 5-HT). The gut microbiota regulates tryptophan (TRP) metabolism and may affect global 5-H synthesis in the enteric and central nervous systems, suggesting a possible involvement of gut microbiota in compulsive spectrum disorders. ObjectivesThe present study investigated whether chronic TRP depletion by diet alters the faecal bacterial community profiles of compulsive versus non-compulsive rats in schedule-induced polydipsia (SIP). Peripheral plasma 5-HT and brain-derived neurotrophic factor (BDNF) levels were evaluated. MethodsWistar rats were selected as High Drinkers (HD) or Low Drinkers (LD) according to their SIP behaviour and were fed for 14 days with either a TRP-free diet (T-) or a TRP-supplemented diet (T+). The faecal bacterial community structure was investigated with 16S rRNA gene-targeted denaturing gradient gel electrophoresis (DGGE) fingerprinting analysis. ResultsCompulsive HD rats showed a lower bacterial diversity than LD rats, irrespectively of the diet. The TRP-depleted HD rats, the only group increasing compulsive licking in SIP, showed a reduction of bacterial evenness and a highly functionally organized community compared with the other groups, indicating that this bacterial community is more fragile to external changes due to the dominance of a low number of species. The chronic TRP depletion by diet effectively reduced peripheral plasma 5-HT levels in both HD and LD rats, while plasma BDNF levels were not altered. ConclusionsThese results highlight the possible implication of reduced microbial diversity in compulsive behaviour and the involvement of the serotonergic system in modulating the gut brain-axis in compulsive spectrum disorders.

Gut Microbiota in Bone Health and Diabetes

Patients with diabetes mellitus (DM) are at increased risk of developing osteopathogenesis and skeletal fragility. The role of the gut microbiota in both DM and osteopathy is not fully explored and may be involved in the pathology of both diseases. Gut microbiota alterations have been observed in DM and osteopathogenic disorders as compared with healthy controls, such as significantly lower abundance of Prevotella and higher abundance of Lactobacillus, with a diminished bacterial diversity. Other overlapping gastro-intestinal features include the loss of intestinal barrier function with translocation of bacterial metabolites to the blood stream, induction of immunological deficits and changes in hormonal and endocrinal signalling, which may lead to the development of diabetic osteopathy. Signalling pathways involved in both DM and osteopathy are affected by gut bacteria and their metabolites. Future studies should focus on gut microbiota involvement in both diseases.

Post-translational suppression of the high affinity IgE receptor expression on mast cells by an intestinal bacterium

Mast cells, which express the high-affinity IgE receptor (FcεRI) on their surface, play a crucial role in inducing allergic inflammation. Since mast cells are activated by crosslinking of FcεRI with IgE and allergens, the cell surface expression level of FcεRI is an important factor in determining the sensitivity to allergens. Recently, the involvement of gut microbiota in the prevalence and regulation of allergy has attracted attention but the precise underlying mechanisms are not fully understood. In this study, the effect of intestinal bacteria on cell surface expression of FcεRI was examined. Bacteroides acidifaciens type A 43 specifically suppressed cell surface expression of FcεRI on mouse bone marrow-derived mast cells (BMMCs) without reduction in FcεRI α and β-chain mRNA and total protein expression. The suppressive effect required sustained exposure to this bacterium, with a corresponding reduction in Erk activation. Inhibition of Erk decreased cell surface distribution of FcεRI in BMMCs, at least in part, through facilitated endocytosis of FcεRI. These results indicate that B. acidifaciens type A 43 suppresses cell surface expression of FcεRI on mast cells in a post-translational manner via inhibition of Erk. The suppression of FcεRI expression on mast cells by specific bacteria might be the underlying mechanism involved in the regulation of allergy by gut microbiota.

Elucidation of Essential Fatty Acid Metabolite Functions in the Immune System and the Involvement of Gut Microbiota

Elucidation of Essential Fatty Acid Metabolite Functions in the Immune System and the Involvement of Gut Microbiota