ABSTRACT
Microbes, used collectively to describe bacteria, fungi, archaea, other unicellular organisms, and viruses, are everywhere. We are increasingly aware of their critical importance to human health: it is estimated that in the human body bacteria alone are as numerous as human cells (Sender et al. 2016), and in terms of gene content and function we are vastly outnumbered (Qin et al. 2010). Microbes contribute to the breakdown of food into accessible nutrients (Hooper et al. 2002; Smith et al. 2013), outcompete invading pathogens in the gut, on the skin and in the urogenital tract (Smits et al. 2016; Grice & Segre 2011; Hickey et al. 2012; Roubaud-Baudron et al. 2019), and affect our mood and behavior through metabolite signaling in the gut (Johnson & Foster 2018). Studying the human microbiome is not only of basic biological interest, but particularly important as we begin to identify associations between changes in composition and most metabolic and autoimmune disorders, including diabetes, obesity, asthma and allergies (Blaser & Falkow 2009). Correlative studies show that the human gut microbiome diversity is lower in populations in developed countries compared to those of hunter-gatherers and inhabitants of rural communities, with the loss suggested to be caused by consumption of less complex and more processed food, increased hygiene, and use of antibiotics (Clemente et al. 2015; Schnorr et al. 2014; Yatsunenko et al. 2012). Cause, effect, and mechanisms are studied in vivo in mouse models, and in vitro in cell cultures such as organoids, complemented by an increasing number of large-scale observational studies in human patients and the first randomized trials, as discussed later.
