Core-shell commensal biocapsules for <i>in situ</i> gut microbiome engineering.

Abstract

Despite the profound influence that gut microbiome composition has on human health, the development of live microbe treatments is constrained by a lack of knowledge on single-species functions within the gastrointestinal (GI) tract. A key barrier is the absence of broadly accessible tools capable of overcoming colonization resistance and enabling spatiotemporal control of microbiome ecology. To address this gap, we have developed a core-shell capsular material, termed a biocapsule, designed to promote the engraftment of a defined bacterial payload to a modified GI niche, thereby enabling precision engineering of commensal populations <i>in situ</i>. To achieve this, biocapsules employ a sequential kill-and-replace strategy in which local native flora are transiently cleared by the capsule before a delivered commensal consortium is introduced to occupy the vacated niche. This targeted antagonism approach is a unique departure from traditional methods that utilize broad-spectrum antibiotics or heterogeneous stool microflora to alter microbial populations, neither of which provide the fine control needed to carefully shape the composition of an established community. Consequently, biocapsules offer a self-assembling, biocompatible platform capable of reshaping microbiome composition <i>in situ</i> to advance translational opportunities in materials-enabled commensal engineering.