Antibiotic Treatment Protocols and Germ-Free Mouse Models in Vascular Research

Abstract

The gut microbiota influence host vascular physiology locally in the intestine, but also evoke remote effects that impact distant organ functions. Amongst others, the microbiota affect intestinal vascular remodeling, lymphatic development, cardiac output and vascular function, myelopoiesis, prothrombotic platelet function, and immunovigilance of the host. Experimentally, host-microbiota interactions are investigated by working with animals devoid of symbiotic bacteria, i.e., by the decimation of gut commensals by antibiotic administration, or by taking advantage of germ-free mouse isolator technology. Remarkably, some of the vascular effects that were unraveled following antibiotic treatment were not observed in the germ-free animal models and vice versa. In this review, we will dissect the manifold influences that antibiotics have on the cardiovascular system and their effects on thromboinflammation.

Keywords: antibiotics; germ-free mouse models; microbiota; platelets; thrombosis; vascular function.

Figure 1

Differences and similarities of germ-free (axenic) and broad-spectrum antibiotic-treated mice (decimation of microbes). While both techniques result in the aberrant enlargement of the cecum, GF mice are less susceptible for colonic inflammation, and present elongated villus structures compared to antibiotic treated animals. In both the animal models, absence of gut microbiota alters protein expression levels in the liver. In the bone marrow, the two mouse models present both reduced granulocytes, monocytes and progenitor cells, but higher T cell levels. On the other hand, while B cells in GF animals are increased, in antibiotic-treated counterparts they were reported to be decreased. Both the complete absence and the decimation of the gut microbiota influences vascular physiology and have an effect on vascular disease. Neointimal hyperplasia, a proliferation and inflammation response to arterial injury, was increased in antibiotic treated rats. Antibiotic treatment leads to a diminished development of aortic root lesion. Additionally, germ-free mice were protected from cardiac inflammation and arterial thrombus growth.