Intestinal microbiome modulation by roundworms and consequences for the metabolome

• Applicant: Professorin Dr. Christina Strube, Ph.D.
• Subject Area: Veterinary Medical Science
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 421365943

Infections with the closely related roundworms Ascaris lumbricoides and Ascaris suum, respectively, are of considerable importance for human as well as porcine health. These infections lead to nutrient deficiency, probably caused primarily by an impairment of the intestinal nutrient transport. Nevertheless, the intestinal microbiota may also contribute to metabolic deficiencies. Since roundworms and the intestinal microbiota share the same ecological niche, it seems obvious that they exert influences on each other. An effect of nematode infections on the intestinal microbiota has already been shown in several studies in humans as well as in animals. Preliminary insights regarding A. suum infections in swine exist; however, these are limited to microbial alterations in the proximal colon, which were studied at two time points post infection only. Insights regarding the influence of human A. lumbricoides infections on the intestinal microbiota are limited to faecal samples, which only allow drawing conclusions regarding processes in the distal parts of the large intestine. Furthermore, so far no knowledge exists regarding the parasitic life stages and products which may influence the microbiota, as well as regarding the question whether a single infection has the same effect as a more natural, repeated exposure. Thus, the aim of this study is a comprehensive characterization of the microbial alterations in different intestinal compartments over the course of the A. suum infection in pigs. To this end, the study will take advantage of several experiments which will be carried out in the frame of a project analyzing the intestinal nutrient transport in A. suum-infected pigs. In addition to the analysis of weekly faecal samples, the dissection of one infection group each at three defined time points post infection also allows analysing the microbiota in different intestinal compartments. To additionally draw conclusions regarding functional aspects of the microbiota, corresponding samples of intestinal content as well as serum samples will also be analysed with regard to the metabolome. The question whether a single infection with A. suum eggs has comparable effects to a continuous exposure will be answered in another experiment. Finally, the planned project will offer insights regarding the question whether only the contact with adult roundworms or their excretory-secretory or somatic antigens, respectively, may be causative for the observed effects. In combination with a current project on the intestinal nutrient transport, this research proposal allows a comprehensive characterization of the parasite-microbiota-host relationship which can be regarded as causative for the nutrient deficiencies in the course of porcine as well as human ascariosis.

• DFG Programme: Research Grants