AUTHOR=Wu Xing , Xu Jiahao , Li Jingbo , Deng Minzi , Shen Zhaohua , Nie Kai , Luo Weiwei , Zhang Chao , Ma Kejia , Chen Xuejie , Wang Xiaoyan 

TITLE=Bacteroides vulgatus alleviates dextran sodium sulfate-induced colitis and depression-like behaviour by facilitating gut-brain axis balance

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1287271

DOI=10.3389/fmicb.2023.1287271

ISSN=1664-302X

ABSTRACT=<sec id="sec1"><title>Background</title><p>Patients with inflammatory bowel disease (IBD) have a higher prevalence of depression. Gut microbiota dysbiosis plays an important role in IBD and depression. However, few studies have explored the characteristic microbiota of patients with IBD and depression (IBDD), or their role in IBDD.</p></sec><sec id="sec2"><title>Methods</title><p>We performed deep metagenomic sequencing and 16S rDNA quantitative PCR to characterise the gut microbial communities of patients with IBDD and patients with IBD without depression (IBDND). We then assessed the effect of the microbiota on colitis and depression in mouse models of dextran sulfate sodium salt (DSS)-induced colitis and lipopolysaccharide (LPS)-induced depression. Furthermore, liquid chromatography–tandem mass spectrometry was used to analyse the microbiota-derived metabolites involved in gut–brain communication. Evans Blue tracer dye was used to assess blood–brain barrier (BBB) permeability.</p></sec><sec id="sec3"><title>Results</title><p>Our results showed that the faecal abundance of <italic>Bacteroides vulgatus</italic> (<italic>B. vulgatus</italic>) was lower in patients with IBDD than in those with IBDND. In the DSS-induced colitis mouse model, the <italic>B. vulgatus</italic> group showed a significantly lower disease activity index score, lesser weight loss, and longer colon length than the DSS group. Moreover, <italic>B. vulgatus</italic> relieved depression-like behaviour in the DSS-induced colitis mouse model and in the LPS-induced depression mouse model. Furthermore, the key metabolite of <italic>B. vulgatus</italic> was p-hydroxyphenylacetic acid (4-HPAA), which was found to relieve intestinal inflammation and alleviate depression-like behaviours in mouse models. By increasing the expression of the tight junction protein claudin-5 in the vascular endothelium of the BBB, <italic>B. vulgatus</italic> and 4-HPAA play critical roles in gut–brain communication.</p></sec><sec id="sec4"><title>Conclusion</title><p><italic>B. vulgatus</italic> and <italic>B. vulgatus</italic>-derived 4-HPAA ameliorated intestinal inflammation and relieved depressive symptoms through the gut–brain axis. Thus, administration of <italic>B. vulgatus</italic> or 4-HPAA supplementation is a promising therapeutic strategy for treating IBD, particularly IBDD.</p></sec>