Interplay Between Human Gut Bacteria Escherichia coli and Lactobacillus mucosae in the Occurrence of Neuropsychiatric Disorders in Mice

Abstract

To understand the roles of human gut bacteria in the occurrence of neuropsychiatric disorders, we isolated inflammatory Escherichia coli K1 and anti-inflammatory Lactobacillus mucosae from healthy human feces and examined their effects on the occurrence of altered microbiota, cognitive decline, and depression in mice. Oral gavage of Escherichia coli K1 caused colitis, cognitive decline, and depression in mice in the elevated plus maze, tail suspension, and forced swimming tasks. However, NK41 treatment reduced K1-induced cognitive decline and anxiety/depression. Furthermore, NK41 treatment increased K1-suppressed brain-derived neurotrophic factor (BDNF) expression and BDNF + /NeuN + cell population and suppressed K1-induced NF-κB activation and LPS + /Iba1 + and NF-κB + /Iba1 + (microglial) cell populations in the hippocampus. NK41 treatment also suppressed K1-induced TNF-α and LPS levels in the blood and TNF-α expression, myeloperoxidase activity, NF-κB + /CD11c + and CD11b + /CD11c + cell populations in the colon. Furthermore, NK41 treatment decreased K1-induced colonic MUC2 expression, gut Proteobacteria population, and fecal LPS levels and modified the bacterial abundance related to polysaccharide breaking and biosynthesis. In conclusion, the overgrowth of inflammatory bacteria such as Escherichia coli in the gastrointestinal tract can cause neuropsychiatric disorders with gut microbiota alteration and the superiority of anti-inflammatory bacteria such as Lactobacillus mucosae can alleviate neuropsychiatric disorders with the attenuation of altered microbiota.

WITHDRAWN: Enterococcus Faecium is a Risk Factor for The Outbreak of Anxiety and Depression in Patients With Inflammatory Bowel Disease

“…Jang et al reported that the overexpression of fecal LPS after exposure to Escherichia coli signi cantly suppressed the expression of tight-junction proteins in the brain and colon [12]. Kim et al reported that Escherichia coli treatment increased the NF-κB + /Iba1 + and LPS + /Iba1 + cell populations in the hippocampus and LPS levels in the blood and feces and decreased the BDNF + /NeuN + cell population and tight-junction protein expression, resulting in the occurrence of depression [29]. Lee et al also reported that oral gavage of Escherichia coli and LPS caused colitis and neuroin ammation in mice through the suppression of tight-junction proteins [38].…”

“…The number of marbles buried for 30 min was counted. The TST was performed on the edge of a table, at 30 cm above it, for 5 min according to the method of Kim et al [29]. Mice were judged to be immobile, when they did not move and hung passively.…”

“…The FST was performed in a round transparent plastic jar (20 × 40 cm 3 ) containing fresh water (25°C) to a height of 25 cm for 5 min, according to Kim et al [29].…”

“…Sectioned tissues were immunostained according to the method of Lee et al [46]. Brie y, the sections were washed with phosphate-buffered saline, blocked with normal serum and incubated with antibodies against NF-κB (p-p65, 1:100, Cell Enzyme-linked immunosorbent assay (ELISA) and immunoblotting Brain and colon tissues were homogenized with radioimmunoprecipitation assay lysis buffer (Biosesang Inc., Seongnam, Korea: cat #RC2002) containing a phosphatase inhibitor cocktail and a 1% protease inhibitor cocktail on ice [29]. For ELISA, the supernatants were transferred into 96-well plates and cytokine levels were determined using ELISA kits (eBioscience, San Diego, CA, USA) [28].…”

“…The fecal microbiota transplantation (FMT) from patients with IBD causes the colitis in transplanted germ-free mice [27,28]. The FMT from mice with colitis causes depression with colitis in transplanted speci c-pathogen-free mice [12,29]. The occurrence of colitis and psychiatric disorder triggered by intestinal environmental factors, such as antibiotics and pathogens, can be attenuated by treatment with commensal Lactobacilli and Bi dobacteria [12,18].…”