Relationship between mucosa-associated gut microbiota and human diseases

The mucus layer covering the gastrointestinal (GI) tract plays a critical role in maintaining gut homeostasis. In the colon, the inner mucus layer ensures commensal microbes are kept at a safe distance from the epithelium while mucin glycans in the outer mucus layer provide microbes with nutrients and binding sites. Microbes residing in the mucus form part of the so-called 'mucosa-associated microbiota' (MAM), a microbial community which, due to its close proximity to the epithelium, has a profound impact on immune and metabolic health by directly impacting gut barrier function and the immune system. Alterations in GI microbial communities have been linked to human diseases. Although most of this knowledge is based on analysis of the faecal microbiota, a growing number of studies show that the MAM signature differs from faecal or luminal microbiota and has the potential to be used to distinguish between diseased and healthy status in well studied conditions such as IBD, IBS and CRC. However, our knowledge about spatial microbial alterations in pathogenesis remains severely hampered by issues surrounding access to microbial communities in the human gut. In this review, we provide state-ofthe-art information on how to access MAM in humans, the composition of MAM, and how changes in MAM relate to changes in human health and disease. A better understanding of interactions occurring at the mucosal surface is essential to advance our understanding of diseases affecting the GI tract and beyond.