“Temporal Variability in Quantitative Human Gut Microbiome Profiles and Implications for Clinical Research”, 2021-11-28 (; similar):
While clinical gut microbiota research is ever-expanding, extending reference knowledge of healthy between-subject and within-subject gut microbiota variation and its drivers remains essential; in particular, temporal variability is under-explored, and a comparison with cross-sectional variation is missing.
Here, we perform daily quantitative microbiome profiling on 713 fecal samples from 20 Belgian women over 6 weeks, combined with extensive anthropometric measurements, blood panels, dietary data, and stool characteristics.
We show substantial temporal variation for most major gut genera; we find that for 78% of microbial genera, day-to-day absolute abundance variation is substantially larger within than between individuals, with up to 100× shifts over the study period. Diversity, and especially evenness indicators also fluctuate substantially. Relative abundance profiles show similar but less pronounced temporal variation. Stool moisture, and to a lesser extent diet, are the only statistically-significant host covariates of temporal microbiota variation, while menstrual cycle parameters did not show statistically-significant effects. We find that the dysbiotic Bact2 enterotype shows increased between-subject and within-subject compositional variability.
Our results suggest that to increase diagnostic as well as target discovery power, studies could adopt a repeated measurement design and/or focus analysis on community-wide microbiome descriptors and indices.
…How many should you collect? Most is gained in the first few samples. Collecting 3 longitudinal samples would allow calculating equilibrium abundances with substantially higher accuracy, as well as estimating temporal variation with a minimum number of samples. It does not matter when you take these samples in a 36-day time interval. Our data indicates fecal microbial communities differ as much from baseline after a day, as they do after one week or one month. While we found substantial variation in bacterial abundance, the collection of bacteria that each person carried did not change much over time. Yet, as expected, whole-community dissimilarity remains generally larger between than within individuals…This observation suggests a dynamic component to the so-called ‘Anna Karenina principle’, which states that dysbiotic communities (Bact2) tend to vary more strongly than non-dysbiotic communities. Consequently, repeated measurements are likely even more important to estimate equilibrium abundances in disease cohorts.