Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review

Abstract

The intestine is the largest interface between the internal body and the external environment. The intestinal barrier is a dynamic system influenced by the composition of the intestinal microbiome and the activity of intercellular connections, regulated by hormones, dietary components, inflammatory mediators, and the enteric nervous system (ENS). Over the years, it has become increasingly evident that maintaining a stable intestinal barrier is crucial to prevent various potentially harmful substances and pathogens from entering the internal environment. Disruption of the barrier is referred to as 'leaky gut' or leaky gut wall syndrome and seems to be characterized by the release of bacterial metabolites and endotoxins, such as lipopolysaccharide (LPS), into the circulation. This condition, mainly caused by bacterial infections, oxidative stress, high-fat diet, exposure to alcohol or chronic allergens, and dysbiosis, appear to be highly connected with the development and/or progression of several metabolic and autoimmune systemic diseases, including obesity, non-alcoholic fatty liver disease (NAFLD), neurodegeneration, cardiovascular disease, inflammatory bowel disease, and type 1 diabetes mellitus (T1D). In this review, starting from a description of the mechanisms that enable barrier homeostasis and analyzing the relationship between this complex ecosystem and various pathological conditions, we explore the role of the gut barrier in driving systemic inflammation, also shedding light on current and future therapeutic interventions.

Keywords: Gut microbiota; Intestinal barrier; Intestinal permeability; Metabolic disease; Systemic inflammation.

Fig. 1

Factors determining intestinal barrier impairment and consequent systemic diseases

Fig. 2

The complex ecosystem of the intestinal barrier. SCFAs Short-chain fatty acids; AMPs antimicrobial peptides; sIgA secretory IgA; TJs tight junctions; IL Interleukin; Th T-helper; T-reg T-regulatory; SFB segmented filamentous bacteria; BAs bile acids; TLR Toll-like receptors; LPS Lipopolysaccharide; GPCR G-protein-coupled receptor; NLRP6 NOD-like receptor family pyrin domain-containing 6; iNOS inducible nitric oxide synthase; PPAR peroxisome proliferator-activated receptor; GLP-1 glucagon-like peptide 1; PYY peptide YY; PI3K Phosphatidyl inositol 3-Kinase; NF-kB Nuclear factor kappa B; IKK NF-kB inhibitors