Manipulating resident microbiota to enhance regulatory immune function to treat inflammatory bowel diseases

Abstract

Altered intestinal microbial composition (dysbiosis) and metabolic products activate aggressive mucosal immune responses that mediate inflammatory bowel diseases (IBD). This dysbiosis impairs the function of regulatory immune cells, which normally promote mucosal homeostasis. Normalizing and maintaining regulatory immune cell function by correcting dysbiosis provides a promising approach to treat IBD patients. However, existing microbe-targeted therapies, including antibiotics, prebiotics, probiotics, and fecal microbial transplantation, provide variable outcomes that are not optimal for current clinical application. This review discusses recent progress in understanding the dysbiosis of IBD and the basis for therapeutic restoration of homeostatic immune function by manipulating an individual patient's microbiota composition and function. We believe that identifying more precise therapeutic targets and developing appropriate rapid diagnostic tools will guide more effective and safer microbebased induction and maintenance treatments for IBD patients that can be applied in a personalized manner.

Ocular Microbiota and Intraocular Inflammation

“…Our recent findings of the existence of intraocular microbes imply that intraocular commensals might also contribute to the pathogenesis of uveitis, as germ-free environment and antibiotics theoretically also remove intraocular commensals, although direct evidence for this notion is still lacking. Therapies manipulating commensal microbiome have been emerged as a novel strategy to prime the host immune system to counteract several inflammatory diseases, such as inflammatory bowel disease, graft-vs.-host disease, HIV infection, and psychological-stress-induced inflammation (125)(126)(127). This is presumably due to the reason that host microbiota could shape the host immune system to dictate the proinflammatory effects of other proinflammatory stimuli (128).…”

Interactions between Intestinal Microflora/Probiotics and the Immune System

“…Aggressive gut microbial strains activate inflammatory response by inducing Th1 and Th17 effector cells while decreased regulatory species inhibit the generation and function of regulatory cells including regulatory T cells (Treg), B cells (Breg), macrophages, dendritic cells (DCs), and innate lymphoid cells (ILCs). This has further resulted in elevated levels of TNF- α and inflammasome and reduced levels of IL-10, TGF- β , and IL-35 [43]. Therefore, dysbiosis of the intestinal flora has contributed to dysfunctional immune system and the chronic inflammation in IBD.…”

Enterobacter Ludwigii Protects Experimental Colitis Through CD103+DC and Treg Cells

“…Gut microbiota alteration is closely associated with IBD occurrence [3], and gut bacterial diversity is reduced in feces and colonic mucosa of IBD patients compared with that of patients in remission [4,5]. Several kinds of bacteria including Bi dobacterium species, Lactobacillus species, Clostridium species, Bacteroides species, Faecalibacterium prausnitzii, Roseburia species, Suterella species, Akkermansia muciniphila, and Eubacteriumhallii, most of which are obligate anaerobic bacteria, have been reported to play roles in reducing in ammation during IBD [6,7]. Aerobes or facultative anaerobes are always hypothesized to contribute to IBD pathogenesis.…”

“…In ammatory response during IBD is caused by induced Th1/Th17 effector cells and impaired regulatory cells including regulatory T cells (Treg), B cells (Breg), M2 macrophages, dendritic cells (CD103 + DCs) and innate lymphoid cells (ILCs) [6,16,17]. Regulatory cell-mediated immune tolerance to foreign antigens and autologous proteins in the colon is important to inhibit IBD [18].…”

“…Tregs play a key role in immunological tolerance through secretion of inhibitory cytokines, and Tregs could disrupt metabolic processes in T effector lymphocytes (Teffs), induce apoptosis of Teffs, trigger cytotoxic activity against Teffs, neutralize DC function, and produce amphiregulin to repair tissue [19]. CD103 + DC promotes Treg differentiation and inhibits Th1/Th17 immune response in mesenteric lymph nodes (MLN) by producing TGF-β, retinoic acid, indoleamine-2,3-dioxygenase (IDO), AhR ligands and carbonic anhydrate I epitope peptide [6,20]. Only a few bacteria have been identi ed to directly induce immune tolerance cells.…”