Microbiota In Pathophysiology Research Articles

Prevalence of perturbed gut microbiota in pathophysiology of arsenic-induced anxiety- and depression-like behaviour in mice

Severe toxic effects of arsenic on human physiology have been of immense concern worldwide. Arsenic causes irrevocable structural and functional disruption of tissues, leading to major diseases in chronically exposed individuals. However, it is yet to be resolved whether the effects result from direct deposition and persistence of arsenic in tissues, or via activation of indirect signaling components. Emerging evidences suggest that gut inhabitants play an active role in orchestrating various aspects of brain physiology, as the gut-brain axis maintains cognitive health, emotions, learning and memory skills. Arsenic-induced dysbiosis may consequentially evoke neurotoxicity, eventually leading to anxiety and depression. To delineate the mechanism of action, mice were exposed to different concentrations of arsenic. Enrichment of Gram-negative bacteria and compromised barrier integrity of the gut enhanced lipopolysaccharide (LPS) level in the bloodstream, which in turn elicited systemic inflammation. Subsequent alterations in neurotransmitter levels, microglial activation and histoarchitectural disruption in brain triggered onset of anxiety- and depression-like behaviour in a dose-dependent manner. Finally, to confirm whether the neurotoxic effects are specifically a consequence of modulation of gut microbiota (GM) by arsenic and not arsenic accumulation in the brain, fecal microbiota transplantations (FMT) were performed from arsenic-exposed mice to healthy recipients. 16S rRNA gene sequencing indicated major alterations in GM population in FMT mice, leading to severe structural, functional and behavioural alterations. Moreover, suppression of Toll-like receptor 4 (TLR4) using vivo-morpholino oligomers (VMO) indicated restoration of the altered parameters towards normalcy in FMT mice, confirming direct involvement of the GM in inducing neurotoxicity through the arsenic-gut-brain axis. This study accentuates the potential role of the gut microbiota in promoting neurotoxicity in arsenic-exposed mice, and has immense relevance in predicting neurotoxicity under altered conditions of the gut for designing therapeutic interventions that will target gut dysbiosis to attenuate arsenic-mediated neurotoxicity.

Gut microbiota in pathophysiology, diagnosis, and therapeutics of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a multifactorial disease, which is thought to be an interplay between genetic, environment, microbiota, and immune-mediated factors. Dysbiosis in the gut microbial composition, caused by antibiotics and diet, is closely related to the initiation and progression of IBD. Differences in gut microbiota composition between IBD patients and healthy individuals have been found, with reduced biodiversity of commensal microbes and colonization of opportunistic microbes in IBD patients. Gut microbiota can, therefore, potentially be used for diagnosing and prognosticating IBD, and predicting its treatment response. Currently, there are no curative therapies for IBD. Microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been recognized as promising therapeutic strategies. Clinical studies and studies done in animal models have provided sufficient evidence that microbiota-based interventions may improve inflammation, the remission rate, and microscopic aspects of IBD. Further studies are required to better understand the mechanisms of action of such interventions. This will help in enhancing their effectiveness and developing personalized therapies. The present review summarizes the relationship between gut microbiota and IBD immunopathogenesis. It also discusses the use of gut microbiota as a noninvasive biomarker and potential therapeutic option.

The role of the gut microbiota and the use of new therapies in Irritable Bowel Syndrome

Introduction: Irritable bowel syndrome is a functional disorder of the gastrointestinal tract with a multifactorial nature of the disease. IBS affects 11% of the population, with the gut microbiota playing an important role in the pathophysiology. Purpose: The aim of this article is to present the course of irritable bowel syndrome, the role of the gut microbiota in pathophysiology, and new therapeutic approaches, including probiotics, based on the current state of knowledge. Conclusions: IBS is a syndrome whose exact pathophysiology is not fully understood. The state of the gut microbiota has a huge impact on the course of the disease, but also on the functioning of the whole body. New therapies currently in use, i.e. probiotics, are showing promising results, but more research is needed to find the golden mean to treat the disease. Methods: Data for the article were retrieved using PubMed setting the time descriptors to 2013-2023. Irritable bowel syndrome is one of the more common functional disorders of the gastrointestinal tract. It manifests as recurrent abdominal pain, discomfort and bloating accompanied by bowel movements without a direct underlying cause. From multicentre clinical studies, it is known that disorders of various mechanisms within the brain-gut axis, altered gastrointestinal motility and visceral hypersensitivity are the underlying causes. In addition, many scholars are of the opinion that disturbances in the gut microbiota play a key role in the pathogenesis of IBS.

THE ROLE OF GUT MICROBIOTA IN PATIENTS WITH DIABETES TYPE 2 AND INSULIN RESISTANCE

Diabetes mellitus is one of the most common chronic disease. In a number of developing and industrialized countries, diabetes mellitus has become an epidemic and is one of the leading causes of death. The rapid increase of cases of type 2 diabetes mellitus (T2DM) in the past decades has made it a widespread metabolic disorder. In recent years, an increasing understanding of how our microflora is linked to obesity-related T2DM has provided a new potential target for reducing the risk of T2DM. The aim of our project is to expand our view on the key roles of microflora during the onset and development of T2DM as well as its complications. Our aim was to study 2 groups of people with T2DM and Prediabetes in order to reveal any gastro-intestinal problems. According to questionnaires, it appeared that patients with diabetes type 2 had 3 or more gastrointestinal disorders, 72 % had bloating, 16% constipation and 12% diarrhea. Patients with prediabetes had 3 and more intestinal disorders: 56 % had bloating, 23% constipation and 21 % diarrhea. Despite, multiple studies supporting the importance of gut microbiota in pathophysiology of T2DM, the field is in early stage. Currently, we have reached a point in our understanding that some probiotics and related molecular mechanisms may be involved in glucose metabolism related to T2DM. We should work towards precision/personalized medicine selecting anti-diabetics and probiotics for a given patient to treat patients successfully.

Advances in the Involvement of Gut Microbiota in Pathophysiology of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and progresses to non-steatohepatitis (NASH) when the liver displays overt inflammatory damage. Increasing evidence has implicated critical roles for dysbiosis and microbiota-host interactions in NAFLD pathophysiology. In particular, microbiota alter intestine absorption of nutrients and intestine permeability, whose dysregulation enhances the delivery of nutrients, endotoxin, and microbiota metabolites to the liver and exacerbates hepatic fat deposition and inflammation. While how altered composition of gut microbiota attributes to NAFLD remains to be elucidated, microbiota metabolites are shown to be involved in the regulation of hepatocyte fat metabolism and liver inflammatory responses. In addition, intestinal microbes and circadian coordinately adjust metabolic regulation in different stages of life. During aging, altered composition of gut microbiota, along with circadian clock dysregulation, appears to contribute to increased incidence and/or severity of NAFLD.

Effects of Western Diet on Giardiasis: A Role for Fatty Acids and Gut Microbiota in the Persistence and Severity of Giardia Infections

AIMSGiardia duodenalis is a protozoan parasite responsible for giardiasis, one of the most common cause of waterborne diseases. Giardia. sp causes epithelial disruptions as well as microbiota alterations. Giardia infections are common in countries with poor sanitation, where the diet is mostly agrarian and high in fiber content. Intriguingly, in such environments, giardiasis has commonly been reported to cause little or no illness. Giardiasis also occurs in developed countries with western/high fat diets, where infections are a common cause of diarrhea. This sutdy investigated the role of diet on the severity and the duration of giardiasis. We hypothesized that western diet may contribute to the persistence of Giardia in the gut. Experiments assessed the role of fatty acids and gut microbiota in pathophysiology.METHODSC57/BL6 mice were fed for two weeks with 5TJN Western diet or 5TJS Low‐Fat (LF) diet prior to infection with Giardia duodenalis GS/M strain (human isolate). The small intestines were collected at day 7 post infection (PI) for histological study and parasite burden. Gut microbiota composition was determined by Illumina Mi‐Seq 16S RNA sequencing. The effect of Oleic and Palmitic acid on Giardia metabolic activity was determined by resazurin assay. Finally, tight junction disruption of small intestinal epithelial cell line SCNB infected with G. duodenalis Assemblage A (NF strain) and Assemblage B (GS/M strain) in the presence of Oleic, Palmitic acid (0.3 mM) or both was determined by immunofluorescence.RESULTSWe observed that Giardia infected C57/BL6 mice that were fed with 5TJN Western diet exhibited a significantly higher trophozoite burden 7 days PI. Giardia infected mice also exhibited more severe mucosal damage (lower villus‐crypt ratio) when fed with Western diet. Fecal microbiota analysis showed that mice fed with Western Diet exhibit a higher abundance of Verrucomicrobia and a lower abundance of Firmicutes than mice fed LF diet. Upon Giardia infection, a decrease of Bacteroidetes and an increase of Firmicutes was observed. Overall, Giardia infection induced an increase of the alpha diversity in Western mice compared to mice given LF diet. Trophozoite metabolic activity was enhanced in the presence of Oleic acid (0.1 mM) and Palmitic acid (0.25mM). In addition, small intestine cell lines infected with G. duodenalis strain NF and GS/M showed a disruption and/or a rearrangement of tight junction proteins such as ZO‐1, Claudin‐1 and 4 when incubated with Oleic and Palmitic acids (0.3 mM).CONCLUSIONThis study gives insight into how diet may influence the outcome of parasitic diseases and intestinal pathophysiology. The findings suggest that a Western Diet may increase the severity of giardiasis by, at least in part, promoting the growth of Giardia through fatty acid supplementation and microbiota modulation. The potential of diet intervention in treatment against parasitic diseases warrants further research.Support or Funding InformationGrant support: NSERCThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Intestinal microbiota in pathophysiology and management of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes. The human intestinal microbiota are composed of more than 1000 different bacterial species and 10(14) cells, and are essential for the development, function, and homeostasis of the intestine, and for individual health. The putative mechanisms that explain the role of microbiota in the development of IBS include altered composition or metabolic activity of the microbiota, mucosal immune activation and inflammation, increased intestinal permeability and impaired mucosal barrier function, sensory-motor disturbances provoked by the microbiota, and a disturbed gut-microbiota-brain axis. Therefore, modulation of the intestinal microbiota through dietary changes, and use of antibiotics, probiotics, and anti-inflammatory agents has been suggested as strategies for managing IBS symptoms. This review summarizes and discusses the accumulating evidence that intestinal microbiota play a role in the pathophysiology and management of IBS.

Functional dysbiosis within the gut microbiota of patients with constipated‐irritable bowel syndrome

The role of the gut microbiota in patho-physiology of irritable bowel syndrome (IBS) is suggested by several studies. However, standard cultural and molecular methods used to date have not revealed specific and consistent IBS-related groups of microbes. To explore the constipated-IBS (C-IBS) gut microbiota using a function-based approach. The faecal microbiota from 14 C-IBS women and 12 sex-match healthy subjects were examined through a combined strictly anaerobic cultural evaluation of functional groups of microbes and fluorescent in situ hybridisation (16S rDNA gene targeting probes) to quantify main groups of bacteria. Starch fermentation by C-IBS and healthy faecal samples was evaluated in vitro. In C-IBS, the numbers of lactate-producing and lactate-utilising bacteria and the number of H(2) -consuming populations, methanogens and reductive acetogens, were at least 10-fold lower (P < 0.05) compared with control subjects. Concomitantly, the number of lactate- and H(2) -utilising sulphate-reducing population was 10 to 100 fold increased in C-IBS compared with healthy subjects. The butyrate-producing Roseburia - E. rectale group was in lower number (0.01 < P < 0.05) in C-IBS than in control. C-IBS faecal microbiota produced more sulphides and H(2) and less butyrate from starch fermentation than healthy ones. A major functional dysbiosis was observed in constipated-irritable bowel syndrome gut microbiota, reflecting altered intestinal fermentation. Sulphate-reducing population increased in the gut of C-IBS and were accompanied by alterations in other microbial groups. This could be responsible for changes in the metabolic output and enhancement in toxic sulphide production which could in turn influence gut physiology and contribute to IBS pathogenesis.