The symbiotic bacterial surface factor polysaccharide A on Bacteroides fragilis inhibits IL-1β-induced inflammation in human fetal enterocytes via toll receptors 2 and 4

Abstract

Colonizing bacteria interacting with the immature, unlike the mature, human intestine favors inflammation over immune homeostasis. As a result, ten percent of premature infants under 1500 grams weight develop an inflammatory necrosis of the intestine after birth, e.g., necrotizing enterocolitis (NEC). NEC is a major health problem in this population causing extensive morbidity and mortality and an enormous expenditure of health care dollars. NEC can be prevented by giving preterm infants their mother’s expressed breast milk or ingesting selective probiotic organisms. Vaginally delivered, breast fed newborns develop health promoting bacteria (“pioneer” bacteria) which preferentially stimulate intestinal host defense and anti-inflammation. One such “pioneer” organism is Bacteroides fragilis with a polysaccharide (PSA) on its capsule. B. fragilis has been shown developmentally in intestinal lymphocytes and dendritic cells to produce a balanced T-helper cell (TH1/TH2) response and to reduce intestinal inflammation by activity through the TLR2 receptor stimulating IL-10 which inhibits IL-17 causing inflammation. No studies have been done on the role of B. fragilis PSA on fetal enterocytes and its increased inflammation. Accordingly, using human and mouse fetal intestinal models, we have shown that B. fragilis with PSA and PSA alone inhibits IL-1β-induced IL-8 inflammation in fetal and NEC intestine. We have also begun to define the mechanism for this unique inflammation noted in fetal intestine. We have shown that B. fragilis PSA anti-inflammation requires both the TLR2 and TLR4 receptor and is in part mediated by the AP1 transcription factor (TLR2) which is developmentally regulated. These observations may help to devise future preventative treatments of premature infants against NEC.

Berberine reduces the occurrence of neonatal necrotizing enterocolitis by reducing the inflammatory response

“…Therefore, the discovery of safe and effective preventive methods has become a research hotspot. Symbiotic bacteria often colonize the sterile gut of neonates, which can increase the incidence of NEC (23). TLRs, cell transmembrane receptors of the natural immune system, are critical for pathogen resistance (24).…”

The Th17/Treg Cell Balance: A Gut Microbiota-Modulated Story

“…In addition, PSA also inhibited Th17 cell differentiation via suppressing the production of Th17-inducing cytokines. For example, PSA on the surface of Bacteroides fragilis inhibited IL-1β-induced inflammation in human fetal enterocytes via TLR2 and TLR4 [82]. In another study, Bacteroides fragilis-induced macrophage IL-1β secretion was shown to upregulate the expression of hepcidin in the liver, a process dependent on the bone morphogenetic protein signaling pathway [83].…”

Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System

“…recently reported that fetal enterocytes exposed to PSA produce lower levels of the IL-1β-induced, pro-inflammatory cytokine IL-8, which may play a role in the development of necrotizing enterocolitis in prematurely born infants (Jiang et al, 2017). …”