Diversity of caecal bacteria is altered in interleukin-10 gene-deficient mice before and after colitis onset and when fed polyunsaturated fatty acids

Abstract

Interleukin-10 gene-deficient (Il10 –/–) mice show a hyper-reaction to normal intestinal bacteria and develop spontaneous colitis similar to that of human Crohn's disease when raised under conventional (but not germ-free) conditions. The lack of IL10 protein in these mice leads to changes in intestinal metabolic and signalling processes. The first aim of this study was to identify changes in the bacterial community of the caeca at 7 weeks of age (preclinical colitis) and at 12 weeks of age (when clinical signs of colitis are present), and establish if there were any changes that could be associated with the mouse genotype. We have previously shown that dietary n-3 and n-6 polyunsaturated fatty acids (PUFA) have anti-inflammatory effects and affect colonic gene expression profiles in Il10 –/– mice; therefore, we also aimed to test the effect of the n-3 PUFA eicosapentaenoic acid (EPA) and the n-6 PUFA arachidonic acid (AA) on the bacterial community of caeca in both Il10 –/– and C57 mice fed these diets. The lower number of caecal bacteria observed before colitis (7 weeks of age) in Il10 –/– compared to C57 mice suggests differences in the intestinal bacteria that might be associated with the genotype, and this could contribute to the development of colitis in this mouse model. The number and diversity of caecal bacteria increased after the onset of colitis (12 weeks of age). The increase in caecal Escherichia coli numbers in both inflamed Il10 –/– and healthy C57 mice might be attributed to the dietary PUFA (especially dietary AA), and thus not be a cause of colitis development. A possible protective effect of E. coli mediated by PUFA supplementation and associated changes in the bacterial environment could be a subject for further investigation to define the mode of action of PUFA in colitis.

Diet as a Therapeutic Option for Adult Inflammatory Bowel Disease

“…Long-chain triglycerides can produce increased lymphocytes fluxes and enhanced proliferative response in intestinal lymph [36], whereas medium chain triglycerides can suppress IL-8, a neutrophil chemottractant expressed in high levels in actively inflamed mucosa of both CD and UC [37, 38]. Fats can also alter the microbiome [39–41] that can lead to upregulation of TLR and NOD mediated inflammation [42–44] and increased intestinal permeability from altered tight junction proteins [45, 46]. Milk derived saturated fats can alter the bile acid composition and allow for growth of sulfate-reducing bacteria such as Bilophila wadsworthia which produce toxic hydrogen sulfide and can aggravate colitis in IL10 knockout mouse models [47–48].…”

Polyunsaturated Fatty Acids in Inflammatory Bowel Diseases

“…86 Dietary PUFA altered diversity of cecal bacteria in mice 87 and IL-10-deficient mice. 88 In vitro and in vivo studies have shown that dietary fats increased small intestinal permeability through three mechanisms: 1) alteration of tight junction protein in rats 83,89 ; 2) modification of cellular membrane composition in T84 IEC 90 ; and 3) through AA-derived eicosanoids production. 91 In contrast, n-3 PUFA prevent this disruption of barrier function.…”

Current and Novel Treatments for Ulcerative Colitis

“…This suggests differences in intestinal bacteria that might be associated with the genotype which could contribute to the development of colitis in this mouse model (88).…”