Immune Response and Microbiota Profiles during Coinfection with Plasmodium vivax and Soil-Transmitted Helminths Alice V. Easton, a Mayra Raciny-Aleman, a,b Victor Liu, a Erica Ruan, a Christian Marier, c Adriana Heguy, c Maria Fernanda Yasnot, b Ana Rodriguez, a P’ng Loke a,d a Department of Microbiology, New York University School of Medicine, New York, New York, USA b Córdoba Microbiological and Biomedical Research Group, Universidad de Córdoba, Montería, Colombia c Genome Technology Center, Division of Advanced Research Technologies, New York University School of Medicine, New York, New York, USA d Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA Alice V. Easton and Mayra Raciny-Aleman contributed equally to this article and are listed alphabetically. Ana Rodriguez and P’ng Loke contributed equally to this article and are listed according to the funding of the study and preparation of the manuscript. ABSTRACT The role of the gut microbiota during coinfection with soil-transmitted helminths (STH) and Plasmodium spp. is poorly understood. We examined peripheral blood and fecal samples from 130 individuals who were either infected with Plasmo- dium vivax only, coinfected with P. vivax and STH, infected with STH alone, or not infected with either P. vivax or STH. In addition to a complete blood count (CBC) with differential, transcriptional profiling of peripheral blood samples was performed by transcriptome sequencing (RNA-Seq), fecal microbial communities were deter- mined by 16S rRNA gene sequencing, and circulating cytokine levels were measured by bead-based immunoassays. Differences in blood cell counts, including an in- creased percentage of neutrophils, associated with a transcriptional signature of neutrophil activation, were driven primarily by P. vivax infection. P. vivax infection was also associated with increased levels of interleukin 6 (IL-6), IL-8, and IL-10; these cytokine levels were not affected by STH coinfection. Surprisingly, P. vivax infection was more strongly associated with differences in the microbiota than STH infection. Children infected with only P. vivax exhibited elevated Bacteroides and reduced Pre- votella and Clostridiaceae levels, but these differences were not observed in indi- viduals coinfected with STH. We also observed that P. vivax parasitemia was higher in the STH-infected population. When we used machine learning to iden- tify the most important predictors of the P. vivax parasite burden (among P. vivax-infected individuals), bacterial taxa were the strongest predictors of para- sitemia. In contrast, circulating transforming growth factor  (TGF-) was the strongest predictor of the Trichuris trichiura egg burden. This study provides un- expected evidence that the gut microbiota may have a stronger link with P. vivax than with STH infection. IMPORTANCE Plasmodium (malaria) and helminth parasite coinfections are frequent, and both infections can be affected by the host gut microbiota. However, the rela- tionship between coinfection and the gut microbiota is unclear. By performing com- prehensive analyses on blood/stool samples from 130 individuals in Colombia, we found that the gut microbiota may have a stronger relationship with the number of P. vivax (malaria) parasites than with the number of helminth parasites infecting a host. Microbiota analysis identified more predictors of the P. vivax parasite burden, whereas analysis of blood samples identified predictors of the helminth parasite bur- den. These results were unexpected, because we expected each parasite to be asso- ciated with greater differences in its biological niche (blood for P. vivax and the in- testine for helminths). Instead, we find that bacterial taxa were the strongest Citation Easton AV, Raciny-Aleman M, Liu V, Ruan E, Marier C, Heguy A, Yasnot MF, Rodriguez A, Loke P. 2020. Immune response and microbiota profiles during coinfection with Plasmodium vivax and soil-transmitted helminths. mBio 11:e01705-20. https://doi.org/ 10.1128/mBio.01705-20. Invited Editor David Serre, University of Maryland, Baltimore Editor Jacques Ravel, University of Maryland School of Medicine This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. Address correspondence to Ana Rodriguez, Ana.Rodriguez@nyumc.org, or P’ng Loke, png.loke@nih.gov. Received 3 July 2020 Accepted 17 September 2020 Published RESEARCH ARTICLE Clinical Science and Epidemiology crossm September/October 2020 Volume 11 Issue 5 e01705-20 ® mbio.asm.org 1 20 October 2020 Downloaded from https://journals.asm.org/journal/mbio on 19 September 2021 by 54.172.52.212.