Prebiotic selection influencing inflammatory bowel disease treatment outcomes: a review of the preclinical and clinical evidence

Abstract

Inflammatory bowel disease (IBD) is characterised by chronic inflammation in the gastrointestinal tract, with unclear aetiology but with known factors contributing to the disease, including genetics, immune responses, environmental factors and dysbiosis of the gut microbiota. Existing pharmacotherapies mainly target the inflammatory symptoms of disease, but recent research has highlighted the capacity for microbial-accessible carbohydrates that confer health benefits (ie, prebiotics) to selectively stimulate the growth of beneficial gut bacteria for improved IBD management. However, since prebiotics vary in source, chemical composition and microbiota effects, there is a clear need to understand the impact of prebiotic selection on IBD treatment outcomes. This review subsequently explores and contrasts the efficacy of prebiotics from various sources (β-fructans, galacto-oligosaccharides, xylo-oligosaccharides, resistant starch, pectin, β-glucans, glucomannans and arabinoxylans) in mitigating IBD symptomatology, when used as either standalone or adjuvant therapies. In preclinical animal colitis models, prebiotics have revealed type-dependent effects in positively modulating gut microbiota composition and subsequent attenuation of disease indicators and proinflammatory responses. While prebiotics have demonstrated therapeutic potential in animal models, clinical evidence for their precise efficacy remains limited, stressing the need for further investigation in human patients with IBD to facilitate their widespread clinical translation as microbiota-targeting IBD therapies.

Keywords: Crohn's Disease; Dietary Fibre; Gastrointestinal Microbiome; Intestinal Microbiota; Ulcerative Colitis.

Figure 1. The chemical structures of all prebiotics discussed in this review and their major food sources. Highlighted in grey are the prebiotic’s monomers.

Figure 2. An overview of the multifaceted effects of prebiotics in rodent models of colitis. (A) Beneficial shift in the gut microbiota of commensal and pathobiont taxa, (B) reduced colitis-induced colon damage, (C) increased SCFA metabolites from prebiotic degradation by the microbiota, (D) modified colonic mRNA expression of enzymes, transcription factors and receptors implicated in the intestinal inflammatory process, (E) changes in the secretion of inflammatory cytokines and (F) enhanced tight junction protein expression that regulates the intestinal epithelial barrier against inflammatory agents. These findings collectively highlight the potential of prebiotics discussed in this review for alleviating colitis symptoms. COX-2, cyclo-oxygenase-2; IL, interleukin; MPO, myeloperoxidase; NF-κB, nuclear factor-κB; nNOS, neuronal nitric oxide synthase; SCFA, short-chain fatty acid; TLR, Toll-like receptor; TNF-α, tumour necrosis factor-α; ZO, zonula occludin.