scholarly journals Long-term dietary patterns are associated with pro-inflammatory and anti-inflammatory features of the gut microbiome

Gut ◽  
2021 ◽  
pp. gutjnl-2020-322670
Author(s):  
Laura A Bolte ◽  
Arnau Vich Vila ◽  
Floris Imhann ◽  
Valerie Collij ◽  
Ranko Gacesa ◽  
...  

ObjectiveThe microbiome directly affects the balance of pro-inflammatory and anti-inflammatory responses in the gut. As microbes thrive on dietary substrates, the question arises whether we can nourish an anti-inflammatory gut ecosystem. We aim to unravel interactions between diet, gut microbiota and their functional ability to induce intestinal inflammation.DesignWe investigated the relation between 173 dietary factors and the microbiome of 1425 individuals spanning four cohorts: Crohn’s disease, ulcerative colitis, irritable bowel syndrome and the general population. Shotgun metagenomic sequencing was performed to profile gut microbial composition and function. Dietary intake was assessed through food frequency questionnaires. We performed unsupervised clustering to identify dietary patterns and microbial clusters. Associations between diet and microbial features were explored per cohort, followed by a meta-analysis and heterogeneity estimation.ResultsWe identified 38 associations between dietary patterns and microbial clusters. Moreover, 61 individual foods and nutrients were associated with 61 species and 249 metabolic pathways in the meta-analysis across healthy individuals and patients with IBS, Crohn’s disease and UC (false discovery rate<0.05). Processed foods and animal-derived foods were consistently associated with higher abundances of Firmicutes, Ruminococcus species of the Blautia genus and endotoxin synthesis pathways. The opposite was found for plant foods and fish, which were positively associated with short-chain fatty acid-producing commensals and pathways of nutrient metabolism.ConclusionWe identified dietary patterns that consistently correlate with groups of bacteria with shared functional roles in both, health and disease. Moreover, specific foods and nutrients were associated with species known to infer mucosal protection and anti-inflammatory effects. We propose microbial mechanisms through which the diet affects inflammatory responses in the gut as a rationale for future intervention studies.

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S028-S029
Author(s):  
L Bolte ◽  
A Vich Vila ◽  
F Imhann ◽  
V Collij ◽  
V Peters ◽  
...  

Abstract Background The gut microbiome directly affects the balance of pro-inflammatory and anti-inflammatory responses in the gut. As microbes thrive on dietary substrates, the question arises whether we can nourish an anti-inflammatory gut ecosystem. In this study, we investigated the relation between 173 dietary factors and the microbiome of 1425 individuals spanning four cohorts: Crohn’s disease, ulcerative colitis, irritable bowel syndrome and the general population. Methods Shotgun metagenomic sequencing was performed to profile gut microbial composition and function. Dietary intake was assessed through food frequency questionnaires. We performed unsupervised clustering to identify dietary patterns and microbial clusters. Next, linear models were conducted between dietary intake and microbial species and pathways, adding age, sex, caloric intake and sequencing read depth as covariates. Analyses were conducted per cohort, followed by a meta-analysis and heterogeneity estimation. Multiple testing correction was performed on the obtained p-values and a FDR &lt;0.05 was defined as significance cut-off. Results We identified 38 associations between dietary patterns and microbial clusters. Moreover, 61 individual foods and nutrients were associated with 61 species and 249 metabolic pathways in the meta-analysis across healthy individuals and patients with IBS, Crohn’s disease and UC (FDR&lt;0.05, heterogeneity p-value&gt;0.05). Processed foods and animal-derived foods were consistently associated with higher abundances of Firmicutes, Ruminococcus species of the Blautia genus and endotoxin synthesis pathways. The opposite associations were found for clusters comprising fish, nuts, bread and legumes. Moreover, while total plant protein intake was associated with a higher Bifidobacterium abundance (FDR=0.048, coef=4.98), animal-derived protein showed a negative association (FDR=1.30x10-05, coef= -4.1). Lastly, we observed positive associations of fecal calprotectin with a fast food cluster (FDR=4.14x10-4, coef=0.24) and a cluster comprised of high-fat meat, potatoes and gravy (FDR=0.003, coef =0.22), while the opposite was seen for clusters of fish and nuts (FDR=0.038, coef= -0.1) and bread and legumes (FDR=0.005, coef= -2.48). Conclusion We identified dietary patterns that consistently correlate with groups of bacteria with shared functional roles in both, health and disease. Moreover, specific foods and nutrients were associated with species known to infer mucosal protection and anti-inflammatory effects. A decrease in these bacteria has already been associated with both IBS and IBD. We propose microbial mechanisms through which the diet affects inflammatory responses in the gut as a rationale for future intervention studies.


2019 ◽  
Vol 13 (11) ◽  
pp. 1439-1449 ◽  
Author(s):  
Marjolein A Y Klaassen ◽  
Floris Imhann ◽  
Valerie Collij ◽  
Jingyuan Fu ◽  
Cisca Wijmenga ◽  
...  

Abstract Background and Aims Crohn’s disease [CD] is a chronic inflammatory disorder of the gastrointestinal tract characterised by alternating periods of exacerbation and remission. We hypothesised that changes in the gut microbiome are associated with CD exacerbations, and therefore aimed to correlate multiple gut microbiome features to CD disease activity. Methods Faecal microbiome data generated using whole-genome metagenomic shotgun sequencing of 196 CD patients were of obtained from the 1000IBD cohort [one sample per patient]. Patient disease activity status at time of sampling was determined by re-assessing clinical records 3 years after faecal sample production. Faecal samples were designated as taken ‘in an exacerbation’ or ‘in remission’. Samples taken ‘in remission’ were further categorised as ‘before the next exacerbation’ or ‘after the last exacerbation’, based on the exacerbation closest in time to the faecal production date. CD activity was correlated with gut microbial composition and predicted functional pathways via logistic regressions using MaAsLin software. Results In total, 105 bacterial pathways were decreased during CD exacerbation (false-discovery rate [FDR] &lt;0.1) in comparison with the gut microbiome of patients both before and after an exacerbation. Most of these decreased pathways exert anti-inflammatory properties facilitating the biosynthesis and fermentation of various amino acids [tryptophan, methionine, and arginine], vitamins [riboflavin and thiamine], and short-chain fatty acids [SCFAs]. Conclusions CD exacerbations are associated with a decrease in microbial genes involved in the biosynthesis of the anti-inflammatory mediators riboflavin, thiamine, and folate, and SCFAs, suggesting that increasing the intestinal abundances of these mediators might provide new treatment opportunities. These results were generated using bioinformatic analyses of cross-sectional data and need to be replicated using time-series and wet lab experiments.


Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 577 ◽  
Author(s):  
Benoît Foligné ◽  
Coline Plé ◽  
Marie Titécat ◽  
Arnaud Dendooven ◽  
Aurélien Pagny ◽  
...  

An original immuno-regulatory strategy against inflammatory bowel diseases based on the use of 28 kDa glutathione S-transferase (P28GST), a unique schistosome protein, was recently proposed. Improvement of intestinal inflammation occurs through restoration of the immunological balance between pro-inflammatory T-helper 1 (Th1) responses and both T-helper 2 (Th2) and regulatory responses. However, detailed mechanisms explaining how P28GST prevents colitis and promotes gut homeostasis remain unknown. Considering the complex interplay between the adaptive and innate immune system and the intestinal microbiota, we raised the question of the possible role of the microbial ecosystem in the anti-inflammatory effects mediated by the helminth-derived P28GST protein. We first analyzed, by 16S rRNA sequencing, the bacterial profiles of mice fecal microbiota at several time points of the P28GST-immunomodulation period prior to trinitrobenzene sulfonic acid (TNBS)-colitis. The influence of gut microbiota in the P28GST-mediated anti-inflammatory effects was then assessed by fecal microbiota transplantation experiments from P28GST-immunized mice to either conventional or microbiota depleted naïve recipient mice. Finally, the experimental data were supplemented by the temporal fecal microbiota compositions of P28GST-treated Crohn’s disease patients from a pilot clinical study (NCT02281916). The P28GST administration slightly modulated the diversity and composition of mouse fecal microbiota while it significantly reduced experimental colitis in mice. Fecal microbiota transplantation experiments failed to restore the P28GST-induced anti-inflammatory effects. In Crohn’s disease patients, P28GST also induced slight changes in their overall fecal bacterial composition. Collectively, these results provide key elements in both the anti-inflammatory mechanisms and the safe therapeutic use of immunomodulation with such promising helminth-derived molecules.


2009 ◽  
Vol 7 (2) ◽  
pp. 97-109 ◽  
Author(s):  
A. De Moreno De Leblanc ◽  
S. Chaves ◽  
G. Perdigón

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, are important problems in industrialized countries. The complete aetiology of both diseases is still unknown but likely involves genetic, environmental and immunological factors. The aim of this work is to study the anti-inflammatory mechanisms reported for yoghurt in a colon cancer model in order to evaluate its usefulness in the treatment of intestinal inflammation such as Crohn's disease. A trinitrobenzenesulfonic acid (TNBS)-induced colitis model was used. The influence of yoghurt feeding was studied before and after TNBS inoculation. The effect on the intestinal microbiota and on the host immune response was evaluated. IgA-producing cells and cells positive for specific cytokines (IL-12, IL-17, IFNγ and IL-10) were analyzed. Yoghurt administration diminished the severity of inflammation in the TNBS-inoculated mice. This effect occurred mainly through IL-10, which was increased in the intestinal tissues throughout the study, and by the decrease observed in IL-17 and IL-12 levels. In addition to this immunomodulatory capacity, another mechanism by which yoghurt could exert the anti-inflammatory activity observed in our model would be through beneficial changes in the intestinal microbiota (increases in the bifidobacteria and lactobacilli populations). These changes in the intestinal microbiota could also be considered one of the causes of the intestinal inflammation reduction. These results show that yoghurt administration modulated the immune response, inducing down regulation of the inflammatory cytokines produced by the immune cells involved in the inflammatory process. The protective effect


1995 ◽  
Vol 108 (4) ◽  
pp. 1056-1067 ◽  
Author(s):  
Anne M. Griffiths ◽  
Arne Ohlsson ◽  
Philip M. Sherman ◽  
Lloyd R. Sutherland

2021 ◽  
Author(s):  
J. J. Teh ◽  
E. M. Berendsen ◽  
E. C. Hoedt ◽  
S. Kang ◽  
J. Zhang ◽  
...  

AbstractThe mucosa-associated microbiota is widely recognized as a potential trigger for Crohn’s disease pathophysiology but remains largely uncharacterised beyond its taxonomic composition. Unlike stool microbiota, the functional characterisation of these communities using current DNA/RNA sequencing approaches remains constrained by the relatively small microbial density on tissue, and the overwhelming amount of human DNA recovered during sample preparation. Here, we have used a novel ex vivo approach that combines microbe culture from anaerobically preserved tissue with metagenome sequencing (MC-MGS) to reveal patient-specific and strain-level differences among these communities in post-operative Crohn’s disease patients. The 16 S rRNA gene amplicon profiles showed these cultures provide a representative and holistic representation of the mucosa-associated microbiota, and MC-MGS produced both high quality metagenome-assembled genomes of recovered novel bacterial lineages. The MC-MGS approach also produced a strain-level resolution of key Enterobacteriacea and their associated virulence factors and revealed that urease activity underpins a key and diverse metabolic guild in these communities, which was confirmed by culture-based studies with axenic cultures. Collectively, these findings using MC-MGS show that the Crohn’s disease mucosa-associated microbiota possesses taxonomic and functional attributes that are highly individualistic, borne at least in part by novel bacterial lineages not readily isolated or characterised from stool samples using current sequencing approaches.


Author(s):  
Ioannis Georgopoulos ◽  
Eleftheria Mavrigiannaki ◽  
Sotiria Stasinopoulou ◽  
Georgios Renieris ◽  
Georgios Nikolakis ◽  
...  

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