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. 2016 Jan 8:6:19032.
doi: 10.1038/srep19032.

Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation

Allison Agus  1 , Jérémy Denizot  1 , Jonathan Thévenot  1   2 , Margarita Martinez-Medina  1 , Sébastien Massier  1 , Pierre Sauvanet  1   3 , Annick Bernalier-Donadille  4 , Sylvain Denis  2 , Paul Hofman  5 , Richard Bonnet  1   6 , Elisabeth Billard  1   7 , Nicolas Barnich  1   7
Affiliations

Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation

Allison Agus et al. Sci Rep. .

Abstract

Recent advances have shown that the abnormal inflammatory response observed in CD involves an interplay among intestinal microbiota, host genetics and environmental factors. The escalating consumption of fat and sugar in Western countries parallels an increased incidence of CD during the latter 20(th) century. The impact of a HF/HS diet in mice was evaluated for the gut micro-inflammation, intestinal microbiota composition, function and selection of an E. coli population. The HF/HS diet created a specific inflammatory environment in the gut, correlated with intestinal mucosa dysbiosis characterized by an overgrowth of pro-inflammatory Proteobacteria such as E. coli, a decrease in protective bacteria, and a significantly decreased of SCFA concentrations. The expression of GPR43, a SCFA receptor was reduced in mice treated with a HF/HS diet and reduced in CD patients compared with controls. Interestingly, mice treated with an agonist of GPR43 were protected against DSS-induced colitis. Finally, the transplantation of feces from HF/HS treated mice to GF mice increased susceptibility to AIEC infection. Together, our results demonstrate that a Western diet could aggravate the inflammatory process and that the activation of the GPR43 receptor pathway could be used as a new strategy to treat CD patients.

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Figures

Figure 1
Figure 1. Western diet causes an inflammatory environment in the digestive tract associated with microbiome perturbations.
WT and CEABAC10 mice were treated with a conventional or an HF/HS diet for 18 weeks (N = 5 per Conv. groups and N = 6 per HF/HS groups) (A) The fecal Lcn-2 levels were measured each week during the treatment (*P < 0.05; **P < 0.01 in WT and CEABAC10 mice under conventional and HF/HS diet; The statistically different Lcn-2 values was determined using a Mann-Whitney test between the diets, for each genotypes. (B) Rarefaction curves of the bacterial species richness, mean values are indicated for each group of mice. (C) PCoA plots based on of the unweighted UniFrac distance matrices showing clustering of mice regarding their global microbiota composition. (D) Relative abundance of phyla in fecal samples between groups of mice.
Figure 2
Figure 2. Western diet favors emergence of E. coli associated with ileal, cecal and colonic mucosa.
(A) E. coli bacteria were isolated from the mucosa by plating on Drigalski agar plates and the number of bacteria was determined by counting the CFU. (B) E. coli colonization of the ileal mucosa of CEABAC10 mice under a conventional or an HF/HS diet was visualized by confocal microscopy and quantification was performed by assessing global fluorescence intensities using the ImageJ software. ****P < 0.0001.
Figure 3
Figure 3. Western diet selects a colitogenic microbiota favoring AIEC colonization.
(A) GF mice receiving a conventional or a HF/HS fecal transplantation were inoculated intragastrically with AIEC LF82. (A) Fecal counts of AIEC LF82 bacteria were performed (B) E. coli colonization of the colonic mucosa was compared between mice transplanted with a fecal pellet from conventional or HF/HS donor mice using confocal microscopy and quantification was performed using the ImageJ software. ****P < 0.0001.
Figure 4
Figure 4. Western diet increases susceptibility to chemically-induced colitis.
(A) Evolution of body weight, (B) DAI at day 9 after DSS treatment and (C) IL-6, KC and IL-1β secretion by colonic mucosa. *P < 0.05; **P < 0.01; ***P < 0.001, ****P < 0.0001 (compared to WT mice under a conventional diet).
Figure 5
Figure 5. Western diet decreases the level of SCFA produced by intestinal microbiota modulating immune response.
(A) Acetate, Butyrate and Propionate in fecal samples were measured by gas chromatography, (B) Treg population in MLN of mice was analyzed by flow cytometry and representative plots gated were obtained on live TCRβ+ MLN cells from conventional or HF/HS fed mice, (C) GPR43 receptor expression was visualized by confocal microscopy and (D) image intensity was quantified using the ImageJ software. *P < 0.05; **P < 0.01; ***P < 0.001, ****P < 0.0001.
Figure 6
Figure 6. GPR43 expression in the intestinal biopsies of patients with CD and controls.
(A) GPR43 immunohistochemical staining of TMA from ileum biopsies of controls, (B) patients in the acute inflamed phase and (C) patients in the quiescent phase of CD. Each spot shows representative tissue immunostaining for GPR43 and for secondary antibody alone (A–C, immunoperoxidase, original magnification ×400). Quantification of GRP43 immunostaining using the Spot Browser software in TMA from ileum biopsies of controls and patients in the acute or quiescent phase of CD, **P < 0.001.
Figure 7
Figure 7. Pharmacological GPR43 activation prevents gut inflammation.
(A) Evolution of body weight, (B) Fecal Lcn-2 levels, (C) DAI at day 8 after the beginning of the treatment and (D) IL-6 and KC cytokine release by colonic mucosa. *P < 0.05; **P < 0.01; ***P < 0.001, ****P < 0.0001.
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