scholarly journals The Gut Microbiota in Celiac Disease and probiotics

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2375 ◽  
Author(s):  
Chibbar ◽  
Dieleman
Keyword(s):  
Celiac Disease ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Healthy Subjects ◽  
Intestinal Inflammation ◽  
Bacterial Populations ◽  
Intestinal Dysbiosis ◽  
Immune Mediated ◽  
Inflammatory State ◽  
Anti Inflammatory

Celiac disease (CeD) is an immune-mediated enteropathy, and unique in that the specific trigger is known: gluten. The current mainstay of therapy is a gluten-free diet (GFD). As novel therapies are being developed, complementary strategies are also being studied, such as modulation of the gut microbiome. The gut microbiota is involved in the initiation and perpetuation of intestinal inflammation in several chronic diseases. Intestinal dysbiosis has been reported in CeD patients, untreated or treated with GFD, compared to healthy subjects. Several studies have identified differential bacterial populations associated with CeD patients and healthy subjects. However, it is still not clear if intestinal dysbiosis is the cause or effect of CeD. Probiotics have also been considered as a strategy to modulate the gut microbiome to an anti-inflammatory state. However, there is a paucity of data to support their use in treating CeD. Further studies are needed with therapeutic microbial formulations combined with human trials on the use of probiotics to treat CeD by restoring the gut microbiome to an anti-inflammatory state.

scholarly journals Children Developing Celiac Disease Have a Distinct and Proinflammatory Gut Microbiota in the First 5 Years of Life

2020 ◽  
Author(s):  
Qian Huang ◽  
Yi Yang ◽  
Vladimir Tolstikov ◽  
Michael A. Kiebish ◽  
Jonas F Ludvigsson ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Plasma Metabolites ◽  
List Type ◽  
Healthy Controls ◽  
Microbiota Composition ◽  
Immune Mediated ◽  
Gut Microbiota Composition

ABSTRACTObjectiveCeliac disease (CD) is an immune-mediated disease characterized by small intestinal inflammation. CD is associated with HLA-DQ2 and HLA-DQ8 haplotypes, however, genetics alone cannot explain the increasing incidence rates. The main goal of this study was to determine the role of the gut microbiota in CD pathogenesis in the first five years of life.DesignWe conducted a longitudinal study focusing on three developmental phases of the gut microbiota (ages 1, 2.5 and 5 years). The fecal samples were obtained from 16 children who developed CD and 16 matched controls. We used 16S sequencing combined with functional analysis, flow cytometry, immunoglobulin A (IgA) sequencing (IgA-seq), and plasma metabolomics to determine a microbial link to CD pathogenesis.ResultsWe identified a distinct gut microbiota composition in CD progressors (CDP, children who developed CD during or after their gut microbiota were sampled) in each developmental phase. Pathogenesis and inflammation-related microbial pathways were enriched in CDP. Moreover, they had significantly more IgA coated bacteria and the IgA targets were significantly different compared to controls. Proinflammatory and pathogenesis-related metabolic pathways were enriched in CDP. Further, we identified inflammatory metabolites, particularly microbiota-derived taurodeoxycholic acid (TDCA) as increased in CDP.ConclusionOur study defines an inflammatory gut microbiota for the CDP including its composition, function, IgA response and related plasma metabolites. The inflammatory nature of CD gut microbiota during development is potentially related to the onset of the disease. Targeting inflammatory bacteria in this critical window could affect the pathogenesis and prognosis of CD.Significance of this studyWhat is already known on this subject?Celiac Disease (CD) is a gluten induced immune-mediated disease in genetically predisposed individuals.CD incidence is increasing worldwide which genetics alone cannot explain. Previous studies have shown that the gut microbiota of CD patients differ from that of healthy populations. However, the role of the microbiome in CD pathogenesis and its role in chronic inflammation is yet be established.What are the new findings?In a prospective longitudinal study in children using samples representing all three phases of gut microbiota development (ages 1, 2.5 and 5), we identified significant differences in the composition and function of gut microbiota at each phase. Pathogenesis and inflammation-related functions are enriched in the gut microbiome of CD progressors.We applied IgA-sequencing to identify inflammatory bacteria in both healthy subjects and CD progressors. Flow Cytometry analysis identified more IgA coated bacteria at ages 1 and 5 in CD progressors, indicating an early inflammatory response. CD bacterial IgA targets also differed significantly from healthy controls.We analyzed plasma metabolites obtained at age 5. The CD plasma metabolome was significantly different from healthy controls. Particularly, proinflammatory plasma metabolites, including microbiota-derived taurodeoxycholic acid (TDCA) and isobutyryl-L-carnitine, were increased two-fold in CD progressors.How might it impact clinical practice in the foreseeable future?Our results establish a link between gut microbiota composition and chronic inflammation in CD during child development. The highly IgA-coated bacteria identified in IgA sequencing and inflammatory bacteria potentially contribute to CD pathogenesis. Targeting these bacteria in the early stages of CD development could be a preventative tool.TDCA is a microbiota-derived proinflammatory metabolite increased two-fold in CD progressors. Increased TDCA levels may be used as a predictive/diagnostic tool in genetically predisposed subjects. Moreover, targeting TDCA-producing bacteria (e.g., Clostridium XIVa species) could potentially help to control the intestinal inflammation in CD.Developing anti-inflammatory probiotics/prebiotics might be viable therapeutics for altering microbiota composition in children genetically predisposed for CD. These microbes/compounds may also complement a gluten-free diet in patients that continue to experience persistent CD symptoms.

scholarly journals Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Stefano Romano ◽  
George M. Savva ◽  
Janis R. Bedarf ◽  
Ian G. Charles ◽  
Falk Hildebrand ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
Meta Analysis ◽  
Gastrointestinal Symptoms ◽  
Short Chain Fatty Acids ◽  
Inflammatory Status

AbstractThe gut microbiota is emerging as an important modulator of neurodegenerative diseases, and accumulating evidence has linked gut microbes to Parkinson’s disease (PD) symptomatology and pathophysiology. PD is often preceded by gastrointestinal symptoms and alterations of the enteric nervous system accompany the disease. Several studies have analyzed the gut microbiome in PD, but a consensus on the features of the PD-specific microbiota is missing. Here, we conduct a meta-analysis re-analyzing the ten currently available 16S microbiome datasets to investigate whether common alterations in the gut microbiota of PD patients exist across cohorts. We found significant alterations in the PD-associated microbiome, which are robust to study-specific technical heterogeneities, although differences in microbiome structure between PD and controls are small. Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, both important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations. This dysbiosis might result in a pro-inflammatory status which could be linked to the recurrent gastrointestinal symptoms affecting PD patients.

Prospective correlation between the patient microbiome with response to and development of immune-mediated adverse effects to immunotherapy in lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21024-e21024
Author(s):  
Justin Chau ◽  
Meeta Yadav ◽  
Ben Liu ◽  
Muhammad Furqan ◽  
Qun Dai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gut Microbiota ◽  
Treatment Response ◽  
Gut Microbiome ◽  
Operational Taxonomic Unit ◽  
Geographic Region ◽  
Organ Function ◽  
Immune Mediated ◽  
Α Diversity ◽  
Clinical Trial Information

e21024 Background: Though the gut microbiome has been associated with immunotherapy (ICI) efficacy in certain cancers, similar correlations between microbiomes at other body sites with treatment response and immune related adverse events (irAEs) in lung cancer (LC) patients receiving ICIs have not been made. We designed a prospective cohort study conducted from 2018-2020 at a single-center academic institution to assess for correlations between the microbiome in various body sites with treatment response and development of irAEs in LC patients treated with ICIs. Methods: Patients with histopathologically confirmed, unresectable/advanced/metastatic LC planned to undergo ICI-based therapy were enrolled between September 2018 and June 2019. Patients must have had measurable disease, ECOG 0-2, and good organ function to be included. Data was collected for analysis from January 2019 to October 2020. Nasal, buccal and gut microbiome samples were obtained prior to ICI initiation, at development of irAEs, improvement of irAEs to grade 1 or less, and at disease progression. 16S rRNA sequenced data was mapped to the SILVA 13.2 database; operational taxonomic unit clusters were analyzed using MicrobiomeAnalyst and METAGENassist. Results: 37 patients were enrolled, and 34 patients were evaluable for this report. 32 healthy controls (HC) from the same geographic region were included to compare baseline gut microbiota. Compared to HC, LC gut microbiota exhibited significantly lower α-diversity. The gut microbiome of patients who did not suffer irAEs were found to have relative enrichment of Bifidobacterium ( p = 0.001) and Desulfovibrio ( p = 0.0002). Responders to combined chemoimmunotherapy exhibited increased Clostridiales ( p = 0.018) but reduced Rikenellaceae ( p = 0.016). In responders to chemoimmunotherapy we also observed enrichment of Finegoldia in nasal microbiome, and increased Megasphaera but reduced Actinobacillus in buccal samples. Longitudinal samples exhibited a trend of α-diversity and certain microbial changes during the development and resolution of irAEs. Conclusions: This pilot study identified significant differences in the gut microbiome between HC and LC patients, and correlates specific bacterial genera to ICI response and irAEs in LC. In addition, it suggests potential predictive utility in nasal and buccal microbiomes, warranting further validation with a larger cohort and mechanistic dissection using preclinical models. Clinical trial information: NCT03688347.

scholarly journals The Role of the Gut Microbiome in Colorectal Cancer

2018 ◽  
Vol 31 (03) ◽  
pp. 192-198 ◽  
Author(s):  
Grace Chen
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Microbial Community ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Intestinal Health ◽  
Genotoxic Effects ◽  
Bacterial Populations ◽  
Health And Disease

AbstractThere is increasing evidence that the gut microbiome, which consists of trillions of microbes representing over 1,000 species of bacteria with over 3 million genes, significantly impacts intestinal health and disease. The gut microbiota not only is capable of promoting intestinal homeostasis and antitumor responses but can also contribute to chronic dysregulated inflammation as well as have genotoxic effects that lead to carcinogenesis. Whether the gut microbiota maintains health or promotes colon cancer may ultimately depend on the composition of the gut microbiome and the balance within the microbial community of protective and detrimental bacterial populations. Disturbances in the normal balanced state of a healthful microbiome, known as dysbiosis, have been observed in patients with colorectal cancer (CRC); however, whether these alterations precede and cause CRC remains to be determined. Nonetheless, studies in mice strongly suggest that the gut microbiota can modulate susceptibility to CRC, and therefore may serve as both biomarkers and therapeutic targets.

scholarly journals NONSTEROIDAL ANTI-INFLAMMATORY DRUGS AS THERAPEUTIC ALLIES OF THE GUT MICROBIOME ON CHRONIC INFLAMMATION

2020 ◽  
pp. 85
Author(s):  
Fabian Mermans ◽  
Evelien Heiremans ◽  
Maud Van Belleghem ◽  
Axelle Meersschaut ◽  
Emma Hernandez-Sanabria
Keyword(s):  
Drug Metabolism ◽  
Chronic Inflammation ◽  
Gut Microbiome ◽  
Tissue Level ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Vital Functions ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Therapeutic Activities

Our gut harbours around 1014 bacteria of more than 1000 species, accounting for approximately 2 kg of biomass. The gut microbiome plays several vital functions in processes such as the development of the immune system, food digestion and protection against pathogens. For these functions to be beneficial for both host and microbiome, interactions are tightly regulated. Gut and immune cells continuously interact to distinguish among commensal microbiota, harmless foodstuff, and pathogens. A fine balance between inflammatory and anti-inflammatory state is fundamental to protect intestinal homeostasis. Nonsteroidal anti-inflammatories (NSAIDs) are a class of drugs used for management of pain and inflammation. These compounds have heterologous structures but similar therapeutic activities. The target of all NSAIDs are the isoforms of cyclooxygenase enzymes (COX): the primarily constitutive form COX-1, and the inducible from COX-2. Both isoforms catalyse the conversion of arachidonic acid to PGH2, the immediate substrate for specific prostaglandin and thromboxane synthesis. The gut microbiota plays a role in drug metabolism,  resulting in altered bioavailability of these compounds. Additionally, complex host-microbiome interactions lead to modified xenobiotic metabolism and altered expression of genes involved in drug metabolism. These effects can be at gut tissue-level, or distant, including in the liver. Besides the gut microbiome influencing drug metabolism, drugs also impact the microbial communities in the gut. As different drugs exert selective pressures on the gut microbiome,  understanding this bidirectional relationship is crucial for developing effective therapies for managing chronic inflammation.

scholarly journals The Herbal Medicine Scutellaria-Coptis Alleviates Intestinal Mucosal Barrier Damage in Diabetic Rats by Inhibiting Inflammation and Modulating the Gut Microbiota

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Boxun Zhang ◽  
Rensong Yue ◽  
Yuan Chen ◽  
Xiaoying Huang ◽  
Maoyi Yang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Diabetic Rats ◽  
Mucosal Barrier ◽  
Inflammatory Factors ◽  
Pathological State ◽  
Intestinal Mucosal Barrier ◽  
Metabolic Inflammation ◽  
Anti Inflammatory

Recent studies have confirmed that increased intestinal permeability and gut-origin lipopolysaccharide (LPS) translocation are important causes of metabolic inflammation in type 2 diabetes (T2D), but there are no recognized therapies for targeting this pathological state. Scutellaria baicalensis and Coptis chinensis are a classic herbal pair often used to treat diabetes and various intestinal diseases, and repair of intestinal barrier damage may be at the core of their therapeutic mechanism. This study investigated the effects of oral administration of Scutellaria-Coptis (SC) on the intestinal mucosal barrier in diabetic rats and explored the underlying mechanism from the perspective of anti-inflammatory and gut microbiota-modulatory effects. The main results showed that, in addition to regulating glycolipid metabolism disorders and inhibiting serum inflammatory factors, SC could also upregulate the expression levels of the tight junction proteins claudin-1, occludin, and zonula occludens (ZO-1), significantly improve intestinal epithelial damage, and inhibit excessive LPS translocation into the blood circulation. Furthermore, it was found that SC could reduce the levels of the inflammatory factors interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α) in intestinal tissue and that the anti-inflammatory effects involved the TLR-4/TRIF and TNFR-1/NF-κB signalling pathways. Moreover, SC had a strong inhibitory effect on some potential enteropathogenic bacteria and LPS-producing bacteria, such as Proteobacteria, Enterobacteriaceae, Enterobacter, Escherichia-Shigella, and Enterococcus, and could also promote the proliferation of butyrate-producing bacteria, such as Lachnospiraceae and Prevotellaceae. Taken together, the hypoglycaemic effects of SC were related to the protection of the intestinal mucosal barrier, and the mechanisms might be related to the inhibition of intestinal inflammation and the regulation of the gut microbiota.

scholarly journals Aryl hydrocarbon receptor ligand production by the gut microbiota is decreased in celiac disease leading to intestinal inflammation

2020 ◽  
Vol 12 (566) ◽  
pp. eaba0624 ◽  
Author(s):  
Bruno Lamas ◽  
Leticia Hernandez-Galan ◽  
Heather J. Galipeau ◽  
Marco Constante ◽  
Alexandra Clarizio ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Gut Microbiota ◽  
Aryl Hydrocarbon Receptor ◽  
Intestinal Inflammation ◽  
Susceptibility Gene ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Aryl Hydrocarbon ◽  
Pathway Activation ◽  
Gut Microbiota Composition

Metabolism of tryptophan by the gut microbiota into derivatives that activate the aryl hydrocarbon receptor (AhR) contributes to intestinal homeostasis. Many chronic inflammatory conditions, including celiac disease involving a loss of tolerance to dietary gluten, are influenced by cues from the gut microbiota. We investigated whether AhR ligand production by the gut microbiota could influence gluten immunopathology in nonobese diabetic (NOD) mice expressing DQ8, a celiac disease susceptibility gene. NOD/DQ8 mice, exposed or not exposed to gluten, were subjected to three interventions directed at enhancing AhR pathway activation. These included a high-tryptophan diet, gavage with Lactobacillus reuteri that produces AhR ligands or treatment with an AhR agonist. We investigated intestinal permeability, gut microbiota composition determined by 16S rRNA gene sequencing, AhR pathway activation in intestinal contents, and small intestinal pathology and inflammatory markers. In NOD/DQ8 mice, a high-tryptophan diet modulated gut microbiota composition and enhanced AhR ligand production. AhR pathway activation by an enriched tryptophan diet, treatment with the AhR ligand producer L. reuteri, or pharmacological stimulation using 6-formylindolo (3,2-b) carbazole (Ficz) decreased immunopathology in NOD/DQ8 mice exposed to gluten. We then determined AhR ligand production by the fecal microbiota and AhR activation in patients with active celiac disease compared to nonceliac control individuals. Patients with active celiac disease demonstrated reduced AhR ligand production and lower intestinal AhR pathway activation. These results highlight gut microbiota-dependent modulation of the AhR pathway in celiac disease and suggest a new therapeutic strategy for treating this disorder.

Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide

Gut ◽  
2021 ◽  
pp. gutjnl-2020-322599
Author(s):  
Hsin-Chih Lai ◽  
Tzu-Lung Lin ◽  
Ting-Wen Chen ◽  
Yu-Lun Kuo ◽  
Chih-Jung Chang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Chronic Obstructive ◽  
Microbiota Composition ◽  
Active Components ◽  
Toll Like Receptor 4 ◽  
Obstructive Pulmonary Disease ◽  
Anti Inflammatory ◽  
Gut Microbiota Composition

ObjectiveChronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.DesignA murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.ResultsGut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.ConclusionThe gut microbiota–lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.

scholarly journals Iron Biofortified Carioca Bean (Phaseolus vulgaris L.)—Based Brazilian Diet Delivers More Absorbable Iron and Affects the Gut Microbiota In Vivo (Gallus gallus)

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1970 ◽  
Author(s):  
Desirrê Dias ◽  
Nikolai Kolba ◽  
Dana Binyamin ◽  
Oren Ziv ◽  
Marilia Regini Nutti ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Gallus Gallus ◽  
Bacterial Populations ◽  
Microbiome Composition ◽  
Treatment Groups ◽  
Micronutrient Concentration ◽  
Total Body ◽  
And Function

Biofortification aims to improve the micronutrient concentration and bioavailability in staple food crops. Unlike other strategies utilized to alleviate Fe deficiency, studies of the gut microbiota in the context of Fe biofortification are scarce. In this study, we performed a 6-week feeding trial in Gallus gallus (n = 15), aimed to investigate the Fe status and the alterations in the gut microbiome following the administration of Fe-biofortified carioca bean based diet (BC) versus a Fe-standard carioca bean based diet (SC). The tested diets were designed based on the Brazilian food consumption survey. Two primary outcomes were observed: (1) a significant increase in total body Hb-Fe values in the group receiving the Fe-biofortified carioca bean based diet; and (2) changes in the gut microbiome composition and function were observed, specifically, significant changes in phylogenetic diversity between treatment groups, as there was increased abundance of bacteria linked to phenolic catabolism, and increased abundance of beneficial SCFA-producing bacteria in the BC group. The BC group also presented a higher intestinal villi height compared to the SC group. Our results demonstrate that the Fe-biofortified carioca bean variety was able to moderately improve Fe status and to positively affect the intestinal functionality and bacterial populations.

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