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Type 2 Diabetes Associated With Altered Daily Gut Microbe Oscillations

NEW YORK – A team led by researchers in Germany has identified gut microbial oscillations over the span of a single day that appear to be disrupted in individuals with type 2 diabetes (T2D) and other metabolic conditions.

"[W]e demonstrate that loss of circadian rhythmicity affects microbiome features related to the onset and progression of T2D and identified bacterial signatures for metabolic risk profiling in human populations," senior author Dirk Haller, a researcher affiliated with the Technical University of Munich, and his co-authors wrote.

Such results "clearly highlight the need to consider diurnal changes in the gut microbiome for diagnostic and prognostic investigations," they noted. 

As they reported in a paper published in Cell Host & Microbe on Thursday, Haller and his colleagues used high-throughput 16S ribosomal RNA gene sequencing to profile gut microbial community composition in fecal samples from 1,976 individuals from Germany enrolled in the prospective KORA population study, detecting distinct levels of specific bugs across the day in individuals with available time of defecation data.

Digging into these diurnal gut microbiome dynamics, they noted that individuals that had T2D or were obese appeared to lose gut oscillations that involved changes in microbiome levels of dozens of gut bugs. The authors noted that while both obesity and T2D coincided with altered gut microbiome oscillations during the span of a day, there were differences in the operational taxa units involved, hinting that weight "contributes to T2D risk stratification independent of disrupted circadian rhythms in the microbiome."

The team went on to verify the 24-hour gut microbe rhythms in nearly 1,400 more German participants sampled at multiple time points. They also used an unsupervised machine learning method to focus in on a set of 13 oscillating gut bacteria with circadian patterns that are upset in individuals with T2D.

The bacterial signature showed promise for finding and predicting T2D cases in a subset of 699 participants from the KORA cohort, while additional metagenomic sequence data for a subset of 50 study participants with or without T2D or pre-diabetes, each tested twice five years apart, provided a window into some of the gut microbe genes and pathways that are altered when metabolic disease-related microbe oscillations are upended.

"Taken together, loss of diurnal oscillation in gut microbiota composition and associated rhythmic functions may contribute to the development of metabolic disorders," the authors concluded, though they cautioned that "[w]hether disease-associated arrhythmic taxa and their functionality are causally linked to the metabolic phenotype of T2D remains to be studied."

Such diurnal gut microbiome fluctuations may have been largely missed in prior gut microbiome studies that did not track stool sampling time, the team suggested, potentially contributing to the inter-individual and regional variability documented in gut microbial communities.

The authors noted that it may be important to take circadian gut microbe oscillations into account "to better understand the underlying mechanisms of disease-associated microbiome alterations and to validate risk profiles in prospective cohorts."