Metatranscriptomics Uncover Diurnal Functional Shifts in Bacterial Transgenes with Profound Metabolic Effects

Area of Science:

• Microbiome Research
• Metabolic Homeostasis
• Circadian Biology

Background:

• Gut diurnal rhythmicity is crucial for integrity, circadian rhythms, and metabolic homeostasis.
• Previous research primarily focused on microbial composition, neglecting transcriptional dynamics.
• Understanding microbial functional shifts is key to elucidating gut health mechanisms.

Purpose of the Study:

• To characterize diurnal fluctuations in the mouse cecal metatranscriptome and metagenome.
• To investigate the impact of high-fat diet and time-restricted feeding (TRF) on microbial function.
• To identify specific microbial genes and functions contributing to metabolic health benefits of TRF.

Main Methods:

• Analysis of mouse cecal metatranscriptome and metagenome under controlled dietary conditions.
• Utilizing metatranscriptomics to detect time-dependent microbial functional shifts.
• Engineering bacterial systems to assess the functional specificity of candidate genes, such as bile salt hydrolase (bsh).

Main Results:

• Metatranscriptomics revealed TRF-induced, time-dependent microbial functional shifts not detectable by metagenomics alone.
• The bile salt hydrolase (bsh) gene from Dubosiella newyorkensis showed diurnal expression in the TRF group.
• Engineered bsh demonstrated specific deconjugation and amidation activities, and in vivo, improved insulin sensitivity, glucose tolerance, and body composition.

Conclusions:

• Coupling metatranscriptomics with engineered bacterial systems is a powerful approach to uncover time-dependent bacterial functions.
• Dubosiella newyorkensis bsh plays a direct role in the metabolic benefits associated with time-restricted feeding.
• This study provides insights into microbial contributions to health and disease modulated by feeding patterns.