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Rifaximin alters gut microbiota profile, but does not affect systemic inflammation - a randomized controlled trial in common variable immunodeficiency.

ABSTRACT: Common variable immunodeficiency (CVID) patients have reduced gut microbial diversity compared to healthy controls. The reduced diversity is associated with gut leakage, increased systemic inflammation and ten "key" bacteria that capture the gut dysbiosis (dysbiosis index) in CVID. Rifaximin is a broad-spectrum non-absorbable antibiotic known to reduce gut leakage (lipopolysaccharides, LPS) in liver disease. In this study, we explored as a 'proof of concept' that altering gut microbial composition could reduce systemic inflammation, using CVID as a disease model. Forty adult CVID patients were randomized, (1:1) to twice-daily oral rifaximin 550?mg versus no treatment for 2 weeks in an open-label, single-centre study. Primary endpoints were reduction in plasma/serum levels of soluble (s) CD14, sCD25, sCD163, neopterin, CRP, TNF, LPS and selected cytokines measured at 0, 2 and 8 weeks. Secondary endpoint was changes in intra-individual bacterial diversity in stool samples. Rifaximin-use did not significantly change any of the inflammation or gut leakage markers, but decreased gut microbial diversity compared with no treatment (p?=?0.002). Importantly, the gut bacteria in the CVID dysbiosis index were not changed by rifaximin. The results suggest that modulating gut microbiota by rifaximin is not the chosen intervention to affect systemic inflammation, at least not in CVID.

SUBMITTER: Jorgensen SF

PROVIDER: S-EPMC6336782 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Rifaximin alters gut microbiota profile, but does not affect systemic inflammation - a randomized controlled trial in common variable immunodeficiency.

Jørgensen S F SF Macpherson M E ME Bjørnetrø T T Holm K K Kummen M M Rashidi A A Michelsen A E AE Lekva T T Halvorsen B B Trøseid M M Mollnes T E TE Berge R K RK Yndestad A A Ueland T T Karlsen T H TH Aukrust P P Hov J R JR Fevang B B

Scientific reports 20190117 1

Common variable immunodeficiency (CVID) patients have reduced gut microbial diversity compared to healthy controls. The reduced diversity is associated with gut leakage, increased systemic inflammation and ten "key" bacteria that capture the gut dysbiosis (dysbiosis index) in CVID. Rifaximin is a broad-spectrum non-absorbable antibiotic known to reduce gut leakage (lipopolysaccharides, LPS) in liver disease. In this study, we explored as a 'proof of concept' that altering gut microbial compositi ...[more]

PMID: 30655568

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Project description:A substantial proportion of patients with common variable immunodeficiency (CVID) have inflammatory and autoimmune complications of unknown etiology. We have previously shown that systemic inflammation in CVID correlates with their gut microbial dysbiosis. The gut microbiota dependent metabolite trimethylamine N-oxide (TMAO) has been linked to several metabolic and inflammatory disorders, but has hitherto not been investigated in relation to CVID. We hypothesized that TMAO is involved in systemic inflammation in CVID. To explore this, we measured plasma concentrations of TMAO, inflammatory markers, and lipopolysaccharide (LPS) in 104 CVID patients and 30 controls. Gut microbiota profiles and the bacterial genes CutC and CntA, which encode enzymes that can convert dietary metabolites to trimethylamine in the colon, were examined in fecal samples from 40 CVID patients and 86 controls. Furthermore, a food frequency questionnaire and the effect of oral antibiotic rifaximin on plasma TMAO concentrations were explored in these 40 patients. We found CVID patients to have higher plasma concentrations of TMAO than controls (TMAO 5.0 [2.9-8.6] vs. 3.2 [2.2-6.3], p = 0.022, median with IQR). The TMAO concentration correlated positively with tumor necrosis factor (p = 0.008, rho = 0.26), interleukin-12 (p = 0.012, rho = 0.25) and LPS (p = 0.034, rho = 0.21). Dietary intake of meat (p = 0.678), fish (p = 0.715), egg (p = 0.138), dairy products (p = 0.284), and fiber (p = 0.767) did not significantly impact on the TMAO concentrations in plasma, nor did a 2-week course of the oral antibiotic rifaximin (p = 0.975). However, plasma TMAO concentrations correlated positively with gut microbial abundance of Gammaproteobacteria (p = 0.021, rho = 0.36). Bacterial gene CntA was present in significantly more CVID samples (75%) than controls (53%), p = 0.020, potentially related to the increased abundance of Gammaproteobacteria in these samples. The current study demonstrates that elevated TMAO concentrations are associated with systemic inflammation and increased gut microbial abundance of Gammaproteobacteria in CVID patients, suggesting that TMAO could be a link between gut microbial dysbiosis and systemic inflammation. Gut microbiota composition could thus be a potential therapeutic target to reduce systemic inflammation in CVID.

Project description:The aim of current study was to determine variations in sow's gut microbiota, serum immunity, and milk metabolite profile mediated by lysozyme supplementation. Twenty-four pregnant sows were assigned to a control group without supplementation and two treatments with 0.5 kg/t and 1.0 kg/t lysozyme provided in formula feed for 21 days (n = 8 per treatment). Microbiota analysis and metagenomic predictions were based on 16s RNA high-throughput sequencing. Milk metabolome was assessed by untargeted liquid chromatography tandem mass spectrometry. Serum biochemical indicators and immunoglobulins were also determined. Gut microbial diversity of sows receiving 1.0 kg/t lysozyme treatment was significantly reduced after the trial. Spirochaetes, Euryarchaeota, and Actinobacteria significantly increased while Firmicutes showed a remarkable reduction in 1.0 kg/t group compared with control. Lysozyme addition rebuilt sow's gut microbiota to beneficial composition identified by reduced richness of Escherichia coli and increased abundance of Lactobacillus amylovorus. Accordingly, microbial metabolic functions including pyrimidine metabolism, purine metabolism, and amino acid related enzymes were significantly up-regulated in 1.0 kg/t group. Microbial metabolic phenotypes like the richness of Gram-positive bacteria and oxidative stress tolerance were also significantly reduced by lysozyme treatment. Serum alanine transaminase (ALT) activity and IgA levels were significantly down-regulated in the 1.0 kg/t group compared with control, but IgM levels showed a significantly increase in 1.0 kg/t group. Milk metabolites such as L-glutamine, creatine, and L-arginine showed significantly dose-dependent changes after treatment. Overall, lysozyme supplementation could effectively improve the composition, metabolic functions, and phenotypes of sow's gut microbiota and it also benefit sows with better serum immunity and milk composition. This research could provide theoretical support for further application of lysozyme in promoting animal gut health and prevent pathogenic infections in livestock production.

Dataset Information

Rifaximin alters gut microbiota profile, but does not affect systemic inflammation - a randomized controlled trial in common variable immunodeficiency.

Publications

Rifaximin alters gut microbiota profile, but does not affect systemic inflammation - a randomized controlled trial in common variable immunodeficiency.

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