Science

Yun Teng, Yi Ren, Mohammed Sayed, Xin Hu, Chao Lei, Anil Kumar, Elizabeth Hutchins, Jingyao Mu, Zhongbin Deng, Chao Luo, Kumaran Sundaram, Mukesh K. Sriwastva, Lifeng Zhang, Michael Hsieh, Rebecca Reiman, Bodduluri Haribabu, Jun Yan, Venkatakrishna Rao Jala, Donald M. Miller, Kendall Van Keuren-Jensen, Michael L. Merchant, Craig J. McClain, Juw Won Park, Nejat K. Egilmez, and Huang-Ge Zhang

The gut microbiota can be altered by dietary inter- ventions to prevent and treat various diseases. However, the mechanisms by which food products modulate commensals remain largely unknown. We demonstrate that plant-derived exosome-like nano- particles (ELNs) are taken up by the gut microbiota and contain RNAs that alter microbiome composition and host physiology. Ginger ELNs (GELNs) are pref- erentially taken up by Lactobacillaceae in a GELN lipid-dependent manner and contain microRNAs that target various genes in Lactobacillus rhamnosus (LGG). Among these, GELN mdo-miR7267-3p-medi- ated targeting of the LGG monooxygenase ycnE yields increased indole-3-carboxaldehyde (I3A). GELN-RNAs or I3A, a ligand for aryl hydrocarbon re- ceptor, are sufficient to induce production of IL-22, which is linked to barrier function improvement. These functions of GELN-RNAs can ameliorate mouse colitis via IL-22-dependent mechanisms. These findings reveal how plant products and their effects on the microbiome may be used to target specific host processes to alleviate disease.