Lactic Acid Bacteria-Gut-Microbiota-Mediated Intervention towards Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), arises from intricate interactions involving genetics, environment, and pharmaceuticals with an ambiguous pathogenic mechanism. Recently, there has been an increasing utilization of lactic acid bacteria (LAB) in managing IBD, attributed to their ability to enhance intestinal barrier function, mitigate inflammatory responses, and modulate gut microbiota. This review initiates by elucidating the pathogenesis of IBD and its determinants, followed by an exploration of the mechanisms underlying LAB therapy in UC and CD. Special attention is directed towards their influence on intestinal barrier function and homeostasis regulated by gut microbiota. Furthermore, the review investigates the complex interplay among pivotal gut microbiota, metabolites, and pathways associated with inflammation. Moreover, it underscores the limitations of LAB in treating IBD, particularly in light of their varying roles in UC and CD. This comprehensive analysis endeavors to offer insights for the optimized application of LAB in IBD therapy.

Keywords: Crohn’s disease; inflammatory bowel disease; lactic acid bacteria; ulcerative colitis.

Figure 1

Types of Inflammatory Bowel Disease. The red areas indicate inflammation, with CD (A) showing segmental distribution and UC (B) presenting as a continuous lesion.

Figure 2

Inflammatory bowel disease pathogenesis. Risk factors trigger microbial dysbiosis in IBD, reducing SCFA-producing bacteria and increasing Proteobacteria. Intestinal barrier integrity is compromised by decreased E-cadherin, altered goblet cell function (Muc2, RELMβ), and Paneth cell dysfunction (NOD2, ATG16L1). Innate immune dysregulation involves reduced CD14+ macrophages and impaired autophagy. An imbalance between effector and Treg leads to uncontrolled T cell activation and abnormal leukocyte migration in the inflamed intestine. Abbreviations: NOD2: nucleotide-binding oligomerization domain 2; ATG16L1: autophagy related 16 like; Muc2: mucin 2; RELMβ: resistin-like molecule β; TNF-α: tumor necrosis factor-α; IL: interleukin; TGF-β: transforming growth factor-β; Th: helper T cell; Treg: regulatory T cell; NK-T: natural killer/T cell.

Figure 3

The role of LAB in UC. LAB treats and ameliorates UC primarily by improving the intestinal barrier, inhibiting the expression of cytokines, and modulating the gut microbiota. Abbreviations: ROS: reactive oxygen species; NO: nitric oxide; COX-2: cyclooxygenase-2; NF-κB: nuclear factor κ-light-chain-enhancer of activated B cells; IFN-γ: interferon-γ; MPO: myeloperoxidase; Nrf2: nuclear factor erythroid 2-related factor 2; HO-1: heme oxygenase-1; sMaf: small Maf transcription factor; ARE: antioxidant response element.

Figure 4

Differences between UC and CD pathogenesis. In UC (A), lesions are primarily confined to the mucosal layer, characterized by superficial ulcers and crypt abscesses. Conversely, CD (B) is marked by segmental inflammation with transmural involvement, presenting as deep fissuring ulcers and granulomatous inflammation.