Nicotinamide Ameliorates Dextran Sulfate Sodium-Induced Chronic Colitis in Mice through Its Anti-Inflammatory Properties and Modulates the Gut Microbiota.

Kai Kang,Li-Xuan Sang,Yue Sun,Bing Chang,Dan Pan,Elizabeth Soares Fernandes

doi:10.1155/2021/5084713

Kai Kang, Li-Xuan Sang + Show 4 more

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https://doi.org/10.1155/2021/5084713

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Abstract

Vitamin B (nicotinamide (NAM)), one of the most important nutritional components for humans, exerts anti-inflammatory activity. This study was aimed at investigating the effect of NAM on the gut microbiota and short-chain fatty acids (SCFAs) in mice with chronic colitis. Colitis was induced in C57BL/6 male mice by administration of 1.5% dextran sulfate sodium (DSS), and the mice were intraperitoneally injected with normal saline (NS) or NAM. NAM treatment ameliorated weight loss and changes in colon length, disease activity index (DAI) score, and histologic scores. Moreover, enzyme-linked immunosorbent assay (ELISA) analysis of LPL cells revealed that the level of interleukin- (IL-) 6, IL-12p70, IL-1β, tumor necrosis factor- (TNF-) α, interferon- (IFN-) γ, IL-21, and IL-17A was increased, while IL-10 was reduced, in the chronic colitis group compared to the control group, but the levels of all these factors were restored after NAM treatment. Then, 16S rRNA sequencing of the large intestinal content was performed, and analysis of alpha diversity and beta diversity showed that the richness of the gut microbiota was decreased in the DSS group compared to the control group and restored after NAM treatment. In addition, NAM modulated specific bacteria, including Odoribacter, Flexispira, and Bifidobacterium, in the NAM+chronic colitis group. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis indicated that NAM treatment restored disruptions in the functions of the gut microbiota (replication and repair, cell motility) in mice with DSS-induced colitis. Furthermore, NAM also restored the reduction in valeric acid in mice with DSS-induced chronic colitis. Our results suggest that NAM treatment could alleviate DSS-induced chronic colitis in mice by inhibiting inflammation and regulating the composition and function of gut microbiota.

Highlights

Inflammatory bowel disease (IBD), a chronic immune inflammatory response in the gastrointestinal tract, is classified as 2 major forms, Crohn’s disease (CD) and ulcerative colitis (UC) [1, 2]
The effect of NAM on dextran sulfate sodium (DSS)-induced chronic colitis was evaluated by comparing the survival rate, body weight loss, colon length, disease activity index (DAI) score (Figure 3), and large intestinal histology (Figure 4) of mice in the chronic colitis group with those of the NAM+chronic colitis group
–2 1 5 10 15 20 25 30 t (d) disease activity index (DAI); (d) colon length (n = 8)

Summary

Introduction

Inflammatory bowel disease (IBD), a chronic immune inflammatory response in the gastrointestinal tract, is classified as 2 major forms, Crohn’s disease (CD) and ulcerative colitis (UC) [1, 2]. An increase in the frequency of IBD (from 68.6 cases per 100,000 people in 1990 to 89.6 cases per 100,000 people in 2017) in developing countries has become a significant health problem over the last three decades [3]. IBD causes symptoms such as fatigue, diarrhea, and abdominal pain [4]. The pathogenesis of IBD is still not fully understood but appears to be influenced by interplay between genetic factors, environmental factors, immunological factors, and disruption of the intestinal microbiota composition [5]. Current treatment options for IBD are mainly based on conventional methods such as treatment with 5-aminosalicylic acid, corticosteroids, and immunosuppressive drugs; these therapies generally cause significant side effects and a sizable subset of patient relapse [6, 7]. Finding effective treatments for IBD is becoming increasingly important

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