Separation of the effects of small intestinal microbiome-diet interactions on human gut hormone secretion

Microbial regulation of gut hormones is a potential mechanism by which the gut microbiome acts on systemic physiology. However, there are limited systems that permit study of how small intestinal microbes and diet modulate gut hormone secretion. Here we present the platform Culturing and Application of Microbes on Intestinal Organoids (CAMIO) and demonstrate its usage in studying the effects of diet and microbes on gut hormones. We validate that CAMIO supports long-term cultivation of a small intestinal microbiome in different dietary sugars and show that CAMIO permits measurement of gut hormones released from jejunal organoids in response to products of the small intestinal communities. In doing so, we observe differential secretion of ghrelin, PP, and PYY according to whether the microbial communities were grown in glucose-fructose versus sucrose or trehalose. We expect CAMIO to be useful in mechanistically understanding how diet and microbes collectively regulate gut hormones.