Oral delivery of Bifidobacterium longum expressing α-melanocyte-stimulating hormone to combat ulcerative colitis

Abstract

a-Melanocyte-stimulating hormone (a-MSH) is a tridecapeptide derived from proopiomelanocortin that exhibits potent anti-inflammatory properties by regulating the production of inflammatory mediators. This peptide has been well established in several inflammatory models, including inflammatory bowel disease (IBD). However, its extremely short duration in vivo limits its clinical application. To address this limitation, Bifidobacterium was used here as a carrier to deliver a-MSH. We utilized a-MSH-engineered Bifidobacterium against IBD, which is closely linked to immune and intestinal microbiota dysfunction. First, we constructed a Bifidobacterium longum secreting a-MSH (B. longum-a-MSH). We then tested the recombinant a-MSH expression and determined its bioactivity in HT-29 cells. To assess its effectiveness, B. longum-a-MSH was used against an ulcerative colitis (UC) model in rats induced by dextran sulfate sodium. The data showed that a-MSH expression in B. longum-a-MSH was effective, and its biological activity was similar to the synthesized one. This UC model experiment indicated that B. longum-a-MSH successfully colonized the intestinal gut, expressed bioactive a-MSH and had a significant anti-inflammatory effect. The results demonstrate the feasibility of preventing IBD by using B. longum-a-MSH.

Applications of Genetically Modified Immunobiotics with High Immunoregulatory Capacity for Treatment of Inflammatory Bowel Diseases

“…In the first of these reports, preventive daily oral administration of α-MSH-secreting B. longum HB15 (HB15) markedly reduced histopathological damage, increased myeloperoxidase activity, corrected an inflammatory/anti-inflammatory cytokine imbalance, and induced production of the pro-inflammatory factor nitrogen monoxide, overcoming effects caused by DSS colitis in rats. Administration of WT-HB15 improved all the parameters with the exception of nitrogen monoxide production, but to a considerably lower degree than that seen with the recombinant strain (19). In the second report, α-MSH-secreting B. longum HB25 (HB25) was created.…”

“…In 2015, Zhang et al showed that the Treg/Th17 balance that had broken down as a result of DSS colitis was fully restored by gm-NCC2705 through the inhibition of two intracellular signaling pathways for Th17 induction (22). In 2016, the intestinal inflammation amelioration action of different strains of B. longum that produced human α-MSH was reported (19, 20). In the first of these reports, preventive daily oral administration of α-MSH-secreting B. longum HB15 (HB15) markedly reduced histopathological damage, increased myeloperoxidase activity, corrected an inflammatory/anti-inflammatory cytokine imbalance, and induced production of the pro-inflammatory factor nitrogen monoxide, overcoming effects caused by DSS colitis in rats.…”

Cloning and expression of enterovirus 71 capsid protein 1 in a probioticBifidobacterium pseudocatenulatum

“…Codon optimization for increased protein expression in B. longum , such as expression of alpha‐melanocyte‐stimulating hormone (Wei et al . ), antigenic fragments of viral proteins (Shkoporov et al . ), hepatitis C virus non‐structural protein (Takei et al .…”

Enterococcus faecalis sir2-like gene enhances aerobic metabolism of themselves and mitochondrial respiration of mammal cells to bring about improving metabolic syndrome through the PGC-1α pathway

“…Plasmid pBV220‐rho was constructed from pBV220 (Wei et al, ), rho sequence, and rho‐asRNA were inserted into pBV220 and named pBV220‐rho(+) and pBV220‐rho(−), respectively. The plasmid was transformed into E .…”