Interaction between Lipopolysaccharide and Gut Microbiota in Inflammatory Bowel Diseases

Abstract

Lipopolysaccharides (LPSs) are bacterial surface glycolipids, produced by Gram-negative bacteria. LPS is known to determine acute inflammatory reactions, particularly in the context of sepsis. However, LPS can also trigger chronic inflammation. In this case, the source of LPS is not an external infection, but rather an increase in endogenous production, which is usually sustained by gut microbiota (GM), and LPS contained in food. The first site in which LPS can exert its inflammatory action is the gut: both GM and gut-associated lymphoid tissue (GALT) are influenced by LPS and shift towards an inflammatory pattern. The changes in GM and GALT induced by LPS are quite similar to the ones seen in IBD: GM loses diversity, while GALT T regulatory (Tregs) lymphocytes are reduced in number, with an increase in Th17 and Th1 lymphocytes. Additionally, the innate immune system is triggered, through the activation of toll-like receptor (TLR)-4, while the epithelium is directly damaged, further triggering inflammation. In this review, we will discuss the importance of the crosstalk between LPS, GM, and GALT, and discuss the possible implications.

Molecular and Pathophysiological Links between Metabolic Disorders and Inflammatory Bowel Diseases

“…Altered Th17/Treg balance in obesity, T2D, and NAFLD * [85] ↑pro-inflammatory cytokines in DIO mice [86,87] ↑IL-17-producing γδ T cells [87,88] and ↑IFN-γ-producing Th1 and CD8 + T cells [87] in DIO mice ↓IL-22 in db/db, ob/ob, and DIO mice [89] ↓Tregs in DIO mice * [85][86][87]89,90] ↓eosinophils in DIO mice [91] Altered Th1/Th2 [92], Th1/Th17 [93,94], Th1/Treg [95] and/or Th17/Treg balance [92,94,95] in IBD * ↑Th1 responses (↑IFN-γ) in CD * [96,97] ↑Th2 responses (↑IL-4 and IL-5) in UC * [96,98] ↑Th17 (↑IL-17, IL-21, and IL-22) in IBD * [99] ↑Th1 or Th17 responses (↑IFN-γ and IL-17) in CD, and↑NK T (↑IL-13), IL-4, IL-5 in UC [98,100] ↑Th1-like Th17 (↑IFN-γ and IL-17), T17-like Treg in CD [101] ↑Th1-like Treg (↑IFN-γ) in both CD and UC [102] ↑plasticity of ILC3s (NKp44 + NKp46 + ) to ILC1s (NKp44 − NKp46 − ) and ↑plasticity of ILC2s to ILC1s in CD [103,104] ↓ILCreg in IBD [105,106] * Possible links between metabolic disorders and IBD.…”

“…Moreover, it has been demonstrated that CD is associated with either Th1 or Th17 cell-mediated response induced by IL-12 and IL-23, producing IFN-γ and IL-17 as pro-inflammatory signals, whereas UC is associated with, not only the abundance of Th17 cells, but also an atypical Th2-mediated response resulting in the expansion of NKT cells producing IL-13 and increased production of IL-4 and IL-5 [98,100]. As such, it is clear that massively infiltrated Th17 cells producing Th17-related cytokines in excess play a key role in IBD pathogenesis, but the roles of T cell plasticity, particularly Th1/Th17 or Treg/Th17 balances also could not be ruled out [93,94]. Naïve CD4 + T cells can also differentiate into Treg cells, which suppress excessive inflammation to maintain intestinal immune homeostasis [95].…”

Alteration of Gut Microbiota Relates to Metabolic Disorders in Primary Aldosteronism Patients

“…PA patients had a higher relative abundance of lipopolysaccharide biosynthesis in the gut microbiota than healthy controls. Lipopolysaccharides are bacterial surface glycolipids produced by gram-negative bacteria, which can induce inflammatory reactions (33). It was reported that inflammatory factors could alter glucose tolerance and insulin sensitivity (34).…”

Probiotics and Trained Immunity

“…The study of epigenetic modifications addressed by microorganisms was initially focused on pathogenic bacteria, because they were considered mechanisms used to control the host's immunity. The cascade of actions induced by the lipopolysaccharide (LPS), an agonist of host inflammatory signaling responses, which can come from an external source (infection), internal production (microbiote), or as food contamination, is a well-known example [48,49]. However, the study of the epigenetic modifications performed by lactic acid bacteria (LAB) remains largely unexplored.…”