Colonic M1 macrophage is associated with the prolongation of gastrointestinal motility and obesity in mice treated with vancomycin.

Abstract

Gut microbiota plays a pivotal role in not only the gastrointestinal (GI) immune system but also GI motility and metabolism. Antibiotic treatments are likely to affect the gut flora and GI immune system, subsequently disturbing GI motility and body metabolism. In the present study, we investigated antibiotic-induced alterations of body metabolism and GI motility in association with the macrophage profile in the colon. Specific pathogen-free (SPF) mice (ICR; 6 weeks old; female) were orally administered vancomycin (0.2 mg/ml) in drinking water for 5 weeks, and subsequent changes in pathophysiology were observed. The expression of CD80 and CD163 was examined by immunohistochemistry and the expression of cytokines in colonic tissues was evaluated by reverse transcription-quantitative polymerase chain reaction. The gastrointestinal transit time (GITT) was measured by administration of carmine red (6% w/v) solution. In the vancomycin-treated SPF mice, significant increases in body weight, cecum weight and GITT were observed compared with the controls. The number of CD80-positive M1 macrophages and the expression of interferon-γ and interleukin-12 were significantly increased, whereas, the numbers of CD163-positive M2 macrophages in the mucosal and muscular layers were decreased in the colon of vancomycin-treated mice. GITT was positively correlated with the number of CD80-positive M1 macrophages in the colonic mucosa; however, was negatively correlated with the number of CD163-positive M2 macrophages in the mucosal and muscular layers. Therefore, it was suggested that antibiotic treatment affects body metabolism and GI motility, accompanied by alterations in macrophage polarization and cytokine profiles in the colon.