Abstract
Hundreds of clinical studies have demonstrated associations between the human microbiome and disease, yet fundamental questions remain on how we can generalize this knowledge. Results from individual studies can be inconsistent, and comparing published data is further complicated by a lack of standard processing and analysis methods. Here we introduce the MicrobiomeHD database, which includes 28 published case–control gut microbiome studies spanning ten diseases. We perform a cross-disease meta-analysis of these studies using standardized methods. We find consistent patterns characterizing disease-associated microbiome changes. Some diseases are associated with over 50 genera, while most show only 10–15 genus-level changes. Some diseases are marked by the presence of potentially pathogenic microbes, whereas others are characterized by a depletion of health-associated bacteria. Furthermore, we show that about half of genera associated with individual studies are bacteria that respond to more than one disease. Thus, many associations found in case–control studies are likely not disease-specific but rather part of a non-specific, shared response to health and disease.
Highlights
Hundreds of clinical studies have demonstrated associations between the human microbiome and disease, yet fundamental questions remain on how we can generalize this knowledge
For some conditions like inflammatory bowel disease (IBD), an overall difference in the gut microbiota was found within several studies, but no individual microbes were consistently associated with IBD across studies12
We identified over 50 suitable case–control 16S data sets, of which 28 were successfully downloaded, processed, and included in a publicly available database, which we called MicrobiomeHD16
Summary
Hundreds of clinical studies have demonstrated associations between the human microbiome and disease, yet fundamental questions remain on how we can generalize this knowledge. Certain gut-related conditions (e.g., obesity and inflammatory bowel disease) have been extensively studied in human cohorts and in animal experiments, where significant and sometimes causal microbial associations have been shown. For some conditions like inflammatory bowel disease (IBD), an overall difference in the gut microbiota was found within several studies, but no individual microbes were consistently associated with IBD across studies. For other conditions like obesity, multiple meta-analyses have found little to no difference in the gut microbiomes of obese and lean patients, even though the microbiome has been causally linked to obesity in mouse models3, 15 These meta-analyses have been limited by focusing on only one or two diseases, and do not extend their findings across a broader landscape of human disease to answer more general questions about overall patterns of disease-associated microbiome shifts
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