TOPLINE:

A variant of the Aeromonas bacterium promoted colon inflammation in mice and was detected in stools and colon tissue from patients with ulcerative colitis (UC).

METHODOLOGY:

• Suspecting that gut-resident macrophages are compromised in UC, researchers examined macrophages in colon tissues of patients with UC.
• They then conducted experiments in mouse models to confirm the in vitro findings.
• Subsequent examinations included bacteria in fecal samples from patients with UC and in wild-type mice under pathological conditions (ie, normal mice infected with the suspected pathogen).

TAKEAWAY:

• Examination of colon tissue from patients with UC revealed that intestinal macrophages, vital for maintaining the gut’s protective epithelial barrier, were almost completely absent, even in areas not yet showing inflammation.
• Fecal samples from patients with UC contained aerolysin, a toxin produced by a variant of the Aeromonas bacterium, which was selectively lethal to macrophages but not to epithelial cells.
• In mouse models, infection with this macrophage-toxic bacterium (MTB) disrupted gut microphages and increased the infected gut’s susceptibility to inflammation, whereas mutant strains lacking aerolysin did not.
• Pretreating mice with anti-aerolysin antibodies prevented MTB-induced colitis, and an anti-aerolysin ameliorated established disease.
• A real-time polymerase chain reaction assay found that the Aeromonas species was detected more frequently in stools from patients with UC compared with healthy control individuals, and aerolysin also was detected in colon tissues isolated from patients with UC.

IN PRACTICE:

“MTB detection in stool or aerolysin immunostaining in colonic tissue could serve as diagnostic biomarkers,” the authors wrote. “Moreover, our findings point to two potential therapeutic approaches: eradication of MTB through antimicrobial therapy and targeted neutralization of aerolysin activity for both prevention and treatment of UC.”

SOURCE:

Zhihui Jiang of the Medical School of Nanjing University, Nanjing, China, led the study, which was published online in Science.

LIMITATIONS:

This was a preclinical study looking at potential mechanisms underlying UC. Clinical studies are needed to validate the findings and confirm the feasibility and effectiveness of the suggested interventions.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China and Fundamental Research Funds for the Central Universities. Jiang and two coauthors declared being inventors on the patent application submitted by Nanjing NysBio Biotechnology that covers MTB and its virulence factor aerolysin as a diagnostic and therapeutic target for UC.

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.