The human intestinal microbiota of constipated-predominant irritable bowel syndrome patients exhibits anti-inflammatory properties

Gobert, Alain P.; Sagrestani, Giulia; Delmas, Eve; Wilson, Keith T.; Verriere, Thomas G.; Dapoigny, Michel; Del’Homme, Christophe; Bernalier-Donadille, Annick

doi:10.1038/srep39399

Cited by 81 publications

(67 citation statements)

References 49 publications

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“…in individuals with PD. Enrichment in Akkermansia muciniphila is known to be related to longer gastrointestinal passage times . However, we did not find Akkermansia abundances to be related to self‐reported constipation.…”

Section: Discussioncontrasting

confidence: 88%

The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder

et al. 2017

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BackgroundIncreasing evidence connects the gut microbiota and the onset and/or phenotype of Parkinson's disease (PD). Differences in the abundances of specific bacterial taxa have been reported in PD patients. It is, however, unknown whether these differences can be observed in individuals at high risk, for example, with idiopathic rapid eye movement sleep behavior disorder, a prodromal condition of α‐synuclein aggregation disorders including PD.ObjectivesTo compare microbiota in carefully preserved nasal wash and stool samples of subjects with idiopathic rapid eye movement sleep behavior disorder, manifest PD, and healthy individuals.MethodsMicrobiota of flash‐frozen stool and nasal wash samples from 76 PD patients, 21 idiopathic rapid eye movement sleep behavior disorder patients, and 78 healthy controls were assessed by 16S and 18S ribosomal RNA amplicon sequencing. Seventy variables, related to demographics, clinical parameters including nonmotor symptoms, and sample processing, were analyzed in relation to microbiome variability and controlled differential analyses were performed.ResultsDifferentially abundant gut microbes, such as Akkermansia, were observed in PD, but no strong differences in nasal microbiota. Eighty percent of the differential gut microbes in PD versus healthy controls showed similar trends in idiopathic rapid eye movement sleep behavior disorder, for example, Anaerotruncus and several Bacteroides spp., and correlated with nonmotor symptoms. Metagenomic sequencing of select samples enabled the reconstruction of genomes of so far uncharacterized differentially abundant organisms.ConclusionOur study reveals differential abundances of gut microbial taxa in PD and its prodrome idiopathic rapid eye movement sleep behavior disorder in comparison to the healthy controls, and highlights the potential of metagenomics to identify and characterize microbial taxa, which are enriched or depleted in PD and/or idiopathic rapid eye movement sleep behavior disorder. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Section: Discussioncontrasting

confidence: 88%

The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder

et al. 2017

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“…Experiments with the GABAb agonist baclofen have shown that GABAb receptors can reduce gastric mobility in the colon of rabbits (via cholinergic modulation) (Tonini et al 1989). Interestingly, A. muciniphila has been shown to be positively associated with gastrointestinal transit time (Gobert et al 2016; Vandeputte et al 2016). GABA could reach the CNS via blood stream as a lipophilic compound, being able to pass the blood brain barrier.…”

Section: Discussionmentioning

confidence: 99%

Parkinson’s disease-associated alterations of the gut microbiome can invoke disease-relevant metabolic changes

Baldini

Hertel

Sandt

et al. 2019

Preprint

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25 26 Parkinson's disease (PD) is a systemic disease clinically defined by the degeneration of 27 dopaminergic neurons in the brain. While alterations in the gut microbiome composition have 28 been reported in PD, their functional consequences remain unclear. Herein, we first analysed 29 the gut microbiome of patients and healthy controls by 16S rRNA gene sequencing of stool 30 samples from the Luxembourg Parkinson's study (n=147 typical PD cases, n=162 controls). 31All individuals underwent detailed clinical assessment, including neurological examinations 32 and neuropsychological tests followed by self-reporting questionnaires. Second, we predicted 33 the potential secretion for 129 microbial metabolites through personalised metabolic modelling 34 using the microbiome data and genome-scale metabolic reconstructions of human gut 35 microbes. Our key results include: 1. eight genera and nine species changed significantly in 36 their relative abundances between PD patients and healthy controls. 2. PD-associated microbial 37 patterns statistically depended on sex, age, BMI, and constipation. The relative abundances of 38Bilophila and Paraprevotella were significantly associated with the Hoehn and Yahr staging 39 after controlling for the disease duration. In contrast, dopaminergic medication had no 40 detectable effect on the PD microbiome composition. 3. Personalised metabolic modelling of 41 the gut microbiomes revealed PD-associated metabolic patterns in secretion potential of nine 42 microbial metabolites in PD, including increased methionine and cysteinylglycine. The 43 microbial pantothenic acid production potential was linked to the presence of specific non-44 motor symptoms and attributed to individual bacteria, such as Akkermansia muciniphila and 45 Bilophila wardswarthia. Our results suggest that PD-associated alterations of gut microbiome 46 could translate into functional differences affecting host metabolism and disease phenotype. 47

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“…Mono-association of Il10 -/mice with A. muciniphila did not induce signs of intestinal inflammation within three weeks but only mildly activated the immune response based on slightly increased fecal lipocalin-2 concentrations. This result indicates that A. muciniphila did not disturb gut immune homeostasis but was perceived as a non-inflammatory, commensal bacterium by the host immune system as observed for wild type mice, 43 even if the host, the Il10 -/mouse, was genetically predisposed to developing colitis. 20 Indeed, mono-association of NMRI wild type mice with A. muciniphila induces the expression of genes involved in antigen presentation in cecum and upregulates the expression of genes involved in innate and adaptive immune responses in the colon without inducing a pro-inflammatory response in these mice.…”

Section: Discussionmentioning

confidence: 60%

“…These cell numbers are approximately one order of magnitude higher than those detected in humans but in the same range as those reported for monoassociated wild-type mice. 2,43 This suggests that the lack of a pro-inflammatory effect of A. muciniphila is not due to an insufficient colonization efficiency of the A. muciniphila strain used in our experiments. It is important to note that we analyzed the short-term effect of A. muciniphila strain ATCC BAA-835 three weeks after its application.…”

Section: Discussionmentioning

confidence: 76%

“…20 Indeed, mono-association of NMRI wild type mice with A. muciniphila induces the expression of genes involved in antigen presentation in cecum and upregulates the expression of genes involved in innate and adaptive immune responses in the colon without inducing a pro-inflammatory response in these mice. 43 Recently, A. muciniphila was reported to trigger intestinal inflammation in germ-free Il10 -/mice within eight weeks following colonization and to increase colitis in specific-pathogen-free (SPF) Il10 -/mice. 42 In our study we used the type strain of A. muciniphila, which was isolated from human feces, 4 while Ref.…”

Section: Discussionmentioning

confidence: 99%

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Akkermansia muciniphila strain ATCC BAA-835 does not promote short-term intestinal inflammation in gnotobiotic interleukin-10-deficient mice

et al. 2018

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Akkermansia muciniphila is a common member of the intestinal microbiota of healthy human individuals. Its abundance is negatively associated with inflammatory bowel disease and metabolic disorders and the oral administration of A. muciniphila improves the symptoms of metabolic disease in mice. Therefore, A. muciniphila is a promising candidate for the treatment of type-2 diabetes and obesity. However, some studies using animal models of intestinal inflammation reported that A. muciniphila may exacerbate gut inflammation. Because of these contradictory reports the present study aimed to clarify the role of A. muciniphila in the development of intestinal inflammation and the conditions promoting it. For this purpose, the short-term colitogenic potential of A. muciniphila strain ATCC BAA-835 was investigated in colitis-prone, gnotobiotic IL-10-deficient (Il10 -/-) mice. Il10 -/mice mono-associated with A. muciniphila showed no signs of intestinal inflammation based on bodyweight change, histopathological scoring and inflammatory markers. Additional association of the mice with the colitogenic Escherichia coli strain NC101 led to cecal but not colonic inflammation. However, the severity of the inflammation did not exceed that observed in mice mono-associated with E. coli NC101. Il10 -/mice colonized with a simplified human intestinal microbiota showed increased histopathology, but no increase in inflammatory markers. Furthermore, co-colonization with A. muciniphila did not modify histopathology. The turnover of intestinal mucus was similar in all groups despite the mucus-degrading property of A. muciniphila. Overall, the data do not support a short-term pro-inflammatory effect of A. muciniphila strain ATCC BAA-835 in the Il10 -/mouse model for inflammatory bowel disease. ARTICLE HISTORY

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The human intestinal microbiota of constipated-predominant irritable bowel syndrome patients exhibits anti-inflammatory properties

Cited by 81 publications

References 49 publications

The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder

The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder

Parkinson’s disease-associated alterations of the gut microbiome can invoke disease-relevant metabolic changes

Akkermansia muciniphila strain ATCC BAA-835 does not promote short-term intestinal inflammation in gnotobiotic interleukin-10-deficient mice

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