Modelling Human Gut‐Microbiome Interactions in a 3D Bioelectronic Platform

Abstract

The role of the gut microbiome in various aspects of health and disease is now a well‐established concept in modern biomedicine. Numerous studies have revealed links between host health and microbial activity, spanning from digestion and metabolism to autoimmune disorders, stress and neuroinflammation. However, the exact mechanisms underlying this complex cross‐talk still remain a mystery. Conventionally, studies examining host‐microbiome interactions rely on animal models, but translation of such findings into human systems is challenging. Bioengineered models represent a highly promisingapproach for tackling such challenges. Here, a bioelectronic platform, the e‐transmembrane, is used to establish a 3D model of human intestine, to study the effects of microbiota on gut barrier integrity. More specifically, how postbiotics and live bacteria impact the morphology and function of the intestinal barrier is evaluated. e‐Transmembrane devices provide a means for in‐line and label‐free continuous monitoring of host‐microbe cross‐talk using electrochemical impedance spectroscopy, revealing distinct patterns that emerge over 24 hours. Microscopy and quantification of molecular biomarkers further validate the differential effects of each bacterial intervention on the host tissue. In addition, a framework to better study and screen drug candidates and potential therapeutic/dietary interventions, such as postbiotics and probiotics, in more physiologically relevant human models is provided.

Keywords

• 3D cell models
• barrier integrity
• bioelectronics
• gut microbiome
• host‐microbe interactions
• organs‐on‐chips