A team of researchers at the University of Alabama at Birmingham has been awarded a five-year, $3.2 million grant from the National Institute on Aging to investigate the effects of microbiome disruption on Alzheimer’s disease progression.
While previous studies have suggested a connection between alterations in gut microbiota and neurodegenerative diseases, the link between Alzheimer’s and the gut microbiome remains relatively unexplored. The UAB researchers aim to fill this knowledge gap by investigating how disruptions in the microbiome may influence the progression of Alzheimer’s.
The project, entitled Promoting circadian rhythms to optimize gut-to-brain signaling for Alzheimer’s disease, is led by Dr Girish Melkani, an associate professor in the UAB Department of Pathology’s Division of Molecular and Cellular Pathology.
Melkani’s research team will employ a fruit fly model, a well-established system for studying complex biological processes. They will specifically examine the impact of genetic or environmental circadian rhythm disruptions on the composition of the microbiome and the onset and severity of cognitive decline in Alzheimer’s.
The researchers will also explore whether imposing time-restricted feeding, a behavioral intervention involving feeding only during active hours, can restore microbiome balance and mitigate circadian rhythm dysregulation. Probiotics will be introduced into the fly’s diet to assess their potential to improve the gut microbiome.
The project aims to:
- Determine whether the depletion of gut microbiota contributes to Alzheimer’s-induced neurodegeneration.
- Examine whether time-restricted feeding can maintain healthy microbiomes in fruit fly models.
- Investigate the mechanisms underlying disrupted gut-to-brain signaling in fruit fly models of Alzheimer’s.
- Conduct a time-series comparison of the microbiomes in models implementing both a 24-hour eating cycle and time-restricted feeding.
“We’re proposing therapeutic strategies for imposing TRF to promote circadian rhythm and therapeutic probiotic treatments to promote beneficial populations of bacteria for patients with AD,” says Melkani. “This project will provide a deeper molecular understanding of the microbiome association in promoting circadian rhythm using TRF-optimized gut-to-brain signaling. This research will assess the efficacy of a behavioral intervention that could have major potential for adoption in humans.”