How Early-Life Gut Microbiota Alteration Sets Trajectories for Health and Inflammatory Bowel Disease?

Abstract

Inflammatory bowel disease (IBD) is a recurrent chronic inflammatory condition of the intestine without any efficient therapeutic regimens. Gut microbiota, which plays an instrumental role in the development and maturation of the immune system, has been implicated in the pathogenesis of IBD. Emerging evidence has established that early-life events particularly maternal influences and antibiotic treatment are strongly correlated with the health or susceptibility to disease of an individual in later life. Thus, it is proposed that there is a critical period in infancy, during which the environmental exposures bestow a long-term pathophysiological imprint. This notion sheds new light on the development of novel approaches for the treatment, i.e., early interventions, more precisely, the prevention of many uncurable chronic inflammatory diseases like IBD. In this review, we have integrated current evidence to describe the feasibility of the “able-to-be-regulated microbiota,” summarized the underlying mechanisms of the “microbiota-driven immune system education,” explored the optimal intervention time window, and discussed the potential of designing early-probiotic treatment as a new prevention strategy for IBD.

Epithelial Heat Shock Proteins Mediate the Protective Effects of Limosilactobacillus reuteri in Dextran Sulfate Sodium-Induced Colitis

“…Management of IBD has relied on anti-adhesion agents, anti-pro-inflammatory cytokine antibodies (e.g., anti-TNF antibody), and antibiotics. None of which could reverse the gut mucosa damages ( 2 ). Here, we first confirmed that DSS increased the expression of pro-inflammatory cytokines TNF-α ( Tnf ), Il1β , and Ifng , led to gut microbiota dysbiosis, and skewed immune responses in MLNs and the circulation, which in turn could increase intestinal permeability and bacterial translocation, consequently resulting in profound intestinal damage and colitis in young mice.…”

“…Complex interactions between the gut microbiota, the epithelial barrier, and the host immune system determine intestinal homeostasis. A breakdown of regulatory pathways in any of these components may lead to chronic inflammatory conditions and inflammatory bowel disease (IBD) ( 1 , 2 ). Manifestating as Crohn’s disease and ulcerative colitis, IBD affects millions of people worldwide, and the incidence is increasing, especially in the newly industrialized areas, such as Asia ( 1 ).…”

“…Manifestating as Crohn’s disease and ulcerative colitis, IBD affects millions of people worldwide, and the incidence is increasing, especially in the newly industrialized areas, such as Asia ( 1 ). Unfortunately, the precise etiology of IBD remains unclear ( 2 ). Despite multiple contributors to disease pathogenesis, one common feature of IBD is identified, i.e., the disruption of the intestinal barrier or the so-called leaky gut ( 3 ).…”

“…Despite multiple contributors to disease pathogenesis, one common feature of IBD is identified, i.e., the disruption of the intestinal barrier or the so-called leaky gut (3). Animal models (4)(5)(6) and clinical studies (2,7,8) have revealed that impaired gut barrier function may be an initial event of IBD, allowing bacteria to approach and leak through the mucosa. Consequently, it leads to defective microbial clearance and aberrant immunoregulation and provokes an uncontrollable inflammatory signal cascade in the gastrointestinal (GI) tract and the whole body.…”

Understanding exposures and latent disease risk within the National Institute of Environmental Health Sciences Superfund Research Program

“…Also of interest is the role of the microbiome and how changes in gut microbiota early in life can impact windows of susceptibility and later-life disease. 1,14,15 Another mechanism that is gaining attention is environmentally induced somatic mosaicism. Exposures during critical windows of development can affect a person's normal tissue development but may also explain tissue-specific effects of hazards in the adult organism due to genetic mosaicism.…”