Prophylactic Treatment of Undernourished Mice with Cotrimoxazole Induces a Different Profile of Dysbiosis with Functional Metabolic Alterations

Abstract

1.AbstractChildhood malnutrition affects physiology and development, it increases infection rate which may not present clinical signs in severe cases. To overcome this issue, the World Health Organization recommends prophylactic treatment with Cotrimoxazole (SXT) along with nutritional recovery. This treatment is controversial since evidence of reduction in morbidity and mortality is not a consensus and could induce the development of antibiotic resistant bacteria. Moreover, the impact of the use of this wide-spectrum antibiotic on gut microbiota, in a critical period of development and weakness, is unknown. To understand how SXT prophylaxis could affect gut microbiota in undernutrition, we induced protein-energy undernutrition in weaning C57BL/6 mice for three weeks and treated animals with SXT for two weeks. Using 16S rRNA gene sequencing we compared the taxonomic composition and metabolic pathways of control mice, animals submitted to undernutrition (UND), treated with SXT, or undernourished and SXT treated (UND+SXT). Undernutrition protocol was responsible for increasing Bacteroidetes and decreasing Firmicutes abundance. We identified that UND mice had a significant increase in predicted pathways related to metabolic syndromes later in life. The prophylactic SXT treatment alone resulted in significant loss in community richness and beta diversity. In addition, we identified the reduction of 6 families in SXT treated mice, including the butyrate producers Lachnospiraceae and Ruminococcaceae. The double challenge (UND+SXT) resulted in a reduction in Clostridiaceae family and in the urea cycle pathway, both related to the fermentation of amino acids, the intestinal epithelial permeability, and the healthy gut environment. Our results show that SXT prophylaxis during an undernourishment period in young mice did not re-establish the undernourished microbiota community composition similar to healthy controls, but induces a distinct dysbiotic profile, with functional metabolic consequences.