The human microbiome, the huge collection of microbes that live inside and on our body, profoundly affects human health and disease. The human gut flora in particular, which harbor the densest number of microbes, not only break down nutrients and release molecules important for our survival but are also key players in the development of many diseases including infections, inflammatory bowel diseases, cancer, metabolic diseases, autoimmune diseases, and neuropsychiatric disorders.
Most of what we know about human–microbiome interactions is based on correlational studies between disease state and bacterial DNA contained in stool samples using genomic or metagenomic analysis. This is because studying direct interactions between the microbiome and intestinal tissue outside the human body represents a formidable challenge, in large part because even commensal bacteria tend to overgrow and kill human cells within a day when grown on culture dishes. Many of the commensal microbes in the intestine are also anaerobic, and so they require very low oxygen conditions to grow which can injure human cells.
A research team at Harvard’s Wyss Institute for Biologically Inspired Engineering led by the Institute’s Founding Director Donald Ingber has developed a solution to this problem using ‘organ-on-a-chip’ (Organ Chip) microfluidic culture technology. His team is now able to culture a stable complex human microbiome in direct contact with a vascularized human intestinal epithelium for at least 5 days in a human Intestine Chip in which an oxygen gradient is established that provides high levels to the endothelium and epithelium while maintaining hypoxic conditions in the intestinal lumen inhabited by the commensal bacteria. Their “anaerobic Intestine Chip” stably maintained a microbial diversity similar to that in human feces over days and a protective physiological barrier that was formed by human intestinal tissue. The study is published in Nature Biomedical Engineering.
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