Impact of ivermectin on gut microbial ecosystem

Authors: Liu, Linshu; Mahalak, Karley; BOBOKALONOV, JAMSHED - Oak Ridge Institute For Science And Education (ORISE); Narrowe, Adrienne; Firrman, Jenni; Scarino Lemons, Johanna; BITTINGER, KYLE - Children'S Hospital - Philadelphia, Pennsylvania; HU, WEIMING - Children'S Hospital - Philadelphia, Pennsylvania; JONES, STEPHEN - Children'S Hospital - Philadelphia, Pennsylvania; MUSTAFA, AHMED - Children'S Hospital - Philadelphia, Pennsylvania

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/4/2023
Publication Date: 11/9/2023
Citation: Liu, L.S., Mahalak, K.K., Bobokalonov, J.D., Narrowe, A.B., Firrman, J., Scarino Lemons, J.M., Bittinger, K., Hu, W., Jones, S.M., Mustafa, A.M. 2023. Impact of ivermectin on gut microbial ecosystem. International Journal of Molecular Sciences. 24:16125. https://doi.org/10.3390/ijms242216125.
DOI: https://doi.org/10.3390/ijms242216125

Interpretive Summary: Ivermectin (IVM) has shown potent activity in combating a broad variety of intestinal parasites; is also the subject of re-purposing applications with the attempt to treat infectious diseases by bacteria, fungi, and viruses by an oral delivery approach. With this delivery method, IVM reacts with the gut microbiome (GM) in addition to the treatment target. To our knowledge, current works on the impacts of IVM on the GM were undertaken during treatment of ill patients, providing compounding information of influence from disease, IVM and other medicines that might be used, as well as individual genetics. In the present research, the IVM on GM subject was investigated using inocula from healthy adults who had passed strict medical standards screening, the research was performed on a Triple-SHIME (simulator of human intestinal microbial ecosystem) supplied with 3 types of feed representing a regular western diet (RWD), and 2 diets with different types of dietary fibers. It was found that under the experimental conditions IVM introduced minor, temporary effects on GM community, in terms of structure and metabolite production, thus IVM would not be expected to induce dysbiosis or yield adverse effects if given to healthy adults. In addition, the soluble fiber component in feed can protect GM from IVM; the increase of short-chain fatty acids production was predicted by PiCRUST2 and detected during the experiment. Medical researchers and food safety professionals will be benefited from this research.

Technical Abstract: To our best knowledge, information available regarding the influence of ivermectin (IVM) on the gut microbiota was collected from diseased donors, who were treated with IVM or with the combination of IVM and other medicine. Results thus obtained were influenced by multiple elements beyond IVM, such as disease, and other medical treatments. The present research investigated the impact of IVM on the gut microbial structure established in a Triple-SHIME® (simulator of the human intestinal microbial ecosystem), using 3 inocula from 3 healthy adults, who had passed strict medical standards screening, supported by 3 type feeds which includes: regular western diet (RWD), and soluble or insoluble fibers containing RWD, labelled as SWD and IWD, respectively. Under the experimental conditions IVM introduced minor and temporary effects on the gut microbial community, in terms of composition and metabolite production, as revealed by 16S rRNA-tagged sequencing analysis, flow cytometry, and GC-MS. Thus, it was concluded that IVM was not expected to induce dysbiosis or yield adverse effects if administered to healthy adults. In addition, the donor’s starting community exerts an effect on the relationship between IVM and gut microbiome, the soluble fiber component in feed could protect the gut microbiota from IVM; an increase of short-chain fatty acid production was predicted by PiCRUSt2 and detected with IVM treatment.