Human Microbiota-Associated Mice: A Model with Challenges

Abstract

Human microbiota-associated (HMA) mice have been used extensively in gut microbiome research. Here we discuss ecological and evolutionary aspects of the mammalian-gut microbiome interrelationship that confound the application of HMA mice, and propose experimental designs that increase the likelihood for obtaining meaningful findings.

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“…Despite the momentum provided by preclinical microbiome studies, there is a growing appreciation of the challenges in moving this work from bench to bedside (Arrieta et al, 2016;Dinan and Cryan, 2016). This includes the fact that the rodent gastrointestinal tract and microbiota composition differs from the human equivalent (Nguyen et al, 2015).…”

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“…However, previous work shows that, once the new microbiota is established in the new host, its composition changes from the original inoculum 109,111 . Therefore, it would be difficult to make conclusions about the original components of the transferred microbiota.…”

“…Studying germ-free animals has helped us appreciate the importance of the microbiome and the dangers of widespread antibiotic treatment. This model has also allowed scientists to selective colonize them with humanderived microbiota and further understand its function in ways that human studies do not allow [109][110][111] . For instance, in one of the first studies of this kind, Smith and colleagues showed that it is poor diet-associated microbiota that drives growth stunting 110 .…”

“…Though the organism can function without it, all the other systems will be affected, often by secondary effects, potentially leading to over-interpretation regarding the direct functions of the organ. Moreover, in studies involving "humanizedmicrobiome" mice, it is likely that the genetic differences and restricted diet of the mice alters the human inoculum they receive 109,112 . Unfortunately, most studies do not check for such differences, drawing conclusions that may not actually pertain to the initial hypothesis 109 .…”

“…Moreover, in studies involving "humanizedmicrobiome" mice, it is likely that the genetic differences and restricted diet of the mice alters the human inoculum they receive 109,112 . Unfortunately, most studies do not check for such differences, drawing conclusions that may not actually pertain to the initial hypothesis 109 . It is, therefore, important to exercise caution when using such reductionist animal models 112 .…”