Angiogenin maintains gut microbe homeostasis by balancing α-Proteobacteria and Lachnospiraceae

Abstract

ObjectiveAntimicrobial peptides (AMPs) play essential roles in maintaining gut health and are associated with IBD. This study is to elucidate the effect of angiogenin (ANG), an intestine-secreted AMP, on gut microbiota and its relevance with IBD.DesignThe effect of ANG on microbiota and its contribution to colitis were evaluated in different colitis models with co-housing and faecal microbiota transplantation. ANG-regulated bacteria were determined by 16S rDNA sequencing and their functions in colitis were analysed by bacterial colonisation. The species-specific antimicrobial activity of ANG and its underlying mechanism were further investigated with microbiological and biochemical methods. ANG level and the key bacteria were characterised in IBD faecal samples.ResultsANG regulated microbiota composition and inhibited intestinal inflammation. Specifically, Ang1 deficiency in mice led to a decrease in the protective gut commensal strains of Lachnospiraceae but an increase in the colitogenic strains of α-Proteobacteria. Direct binding of ANG to α-Proteobacteria resulted in lethal disruption of bacterial membrane integrity, and consequently promoted the growth of Lachnospiraceae, which otherwise was antagonised by α-Proteobacteria. Oral administration of ANG1 reversed the dysbiosis and attenuated the severity of colitis in Ang1-deficient mice. The correlation among ANG, the identified bacteria and IBD status was established in patients.ConclusionThese findings demonstrate a novel role of ANG in shaping gut microbe composition and thus maintaining gut health, suggesting that the ANG-microbiota axis could be developed as a potential preventive and/or therapeutic approach for dysbiosis-related gut diseases.

Microbiome Crosstalk in Immunotherapy and Antiangiogenesis Therapy

“…Oral administration of Ang-1 is known to restore the intestinal microbiota composition of Ang-1-deficient mice, ultimately relieving colitis. Therefore, targeting Ang could be a potential therapeutic target for intestinal diseases associated with dysbacteriosis ( 117 ).…”

Characteristics of Oral Microbiota in Patients with Esophageal Cancer in China

“…In these studies, a higher abundance of Capnocytophaga in the oral cavity was associated with oral diseases, and it may be a promising biomarker for predicting esophageal squamous cell carcinoma. In a previous study, Lachnospiraceae functioned as a short-chain fatty acid producer [ 35 ], and this family of anaerobic bacteria is reportedly found at relatively low levels in colorectal cancer patients [ 16 , 36 ]. This result is consistent with the present study, in which there was a higher abundance of Lachnospiraceae in healthy individuals.…”

Bacterial Characteristics of Intestinal Tissues From Patients With Crohn’s Disease

“… Leccese et al (2020) found that Lactobacillus acidophilus LA1 or Lactobacillus paracasei 101/37 (belonging to the Lactobacillaceae family, Firmicutes phylum) can effectively reduce adherent-invasive E. coli adhesion to HT29 (human colorectal adenocarcinoma cell), as well as reducing biofilm formation. Sun et al (2021) found that Anaerostipes sp. and Blautia sp.…”