Host-microbiota interaction induces bi-phasic inflammation and glucose intolerance in mice

Area of Science:

• Microbiology
• Metabolic Health
• Host-Microbiome Interactions

Background:

• The gut microbiome plays a crucial role in regulating host metabolism, including adiposity and glucose homeostasis.
• Understanding the temporal dynamics of host-microbiome interactions is essential for deciphering metabolic regulation.

Purpose of the Study:

• To investigate the time-dependent effects of gut microbiota colonization on adiposity and glucose metabolism in germ-free (GF) mice.
• To differentiate the impacts of early-stage colonization versus established microbiome colonization on host metabolic parameters.

Main Methods:

• Germ-free mice were colonized with gut microbiota from conventionally raised (CONV-R) mice.
• Physiological parameters, microbiome composition, serum cytokine levels, and inflammatory gene expression were assessed at multiple time points post-colonization.
• Comparisons were made between newly colonized mice and antibiotic-treated mice that were subsequently re-colonized.

Main Results:

• Gut microbiota colonization induced a biphasic glucose impairment: an early phase (within 3 days) associated with inflammation and independent of adiposity, and a delayed phase (14-28 days) linked to adipose tissue expansion and inflammation.
• Re-colonization of antibiotic-treated mice exhibited only the delayed phase of glucose impairment and adiposity.
• These findings suggest the early phase of glucose impairment is specific to the initial colonization of the immature GF mouse gut.

Conclusions:

• Host-microbiota interactions during initial colonization of GF mice have distinct, time-resolved effects on adiposity and glucose metabolism.
• The study highlights the critical window of early colonization in shaping host metabolic responses.
• These insights contribute to understanding the complex interplay between the gut microbiome and host metabolic health.