Using optogenetics on gut microbes can promote Longevity.
Our guts are full of trillions of bacteria, viruses, protozoa, archaea and fungi, both harmful and beneficial. Collectively they are referred to as the gut microbiome. As well as being vital for maintaining physical health, the gut microbiome plays a key role in regulating aging. However, teasing out how a specific microbial species impacts Longevity has proved challenging; now a team from Baylor College of Medicine is shining a light on the problem.
Longevity.Technology: Interest in the role that the gut microbiome plays in maintaining healthspan and lifespan is growing; from improving mental wellbeing, to direct-to-consumer personalised probiotic solutions based on whole-genome sequencing diagnostics. Indeed, the human microbiome market, which was valued at $351.81m in the year 2018, is continuing to enjoy considerable growth fuelled by rising incidences of diabetes, an aging population and pharmaceutical research. This research, although at an early stage, is nevertheless an exciting step on the journey to personalised gut health working for Longevity.
In order to investigate how bacteria and bacterial products in the gut microbiome influence the aging process, the Baylor team, in conjunction with colleagues at Rice University, developed a method that uses light to directly control gene expression and metabolite production from bacteria that reside in the gut of the laboratory worm Caenorhabditis elegans.
The researchers discovered that production of colanic acid by modified resident E. coli bacteria could be induced by green light and that this acid not only protected cells against stress-induced cellular damage, but extended the roundworm’s lifespan. Colonic acid is an exopolysaccharide that can extend the lifespan of its host C. elegans by “modulating mitochondrial dynamics” .
The research team engineered E. coli to express fluorescent reporter proteins and then further modified the bacteria to biosynthesise the pro-Longevity compound colanic acid in response to green light and switch off its production when exposed to red light.
C. elegans is transparent, so the modified E.coli in the worm’s gut was induced to to produce colanic acid when green light was shone on the worm. The colanic acid protected the worm’s gut cells against stress-induced mitochondrial hyper-fragmentation .
The team believe the optogenetic method could be used to study other bacteria, as well as leading to a process that can precisely refine bacterial metabolism in the host gut in order to deliver health benefits with minimal side effects.
“The stronger the light, the longer the lifespan…”
“We used optogenetics, a method that combines light and genetically engineered light-sensitive proteins to regulate molecular events in a targeted manner in living cells or organisms,” said co-corresponding author Dr Meng Wang, an investigator at Howard Hughes Medical Institute, member of Baylor’s Dan L Duncan Comprehensive Cancer Center and professor of molecular and human genetics and the Huffington Center on Aging at Baylor.
“When exposed to green light, worms carrying this E. coli strain also lived longer,” Dr Wang explained. “The stronger the light, the longer the lifespan. Optogenetics offers a direct way to manipulate gut bacterial metabolism in a temporally, quantitatively and spatially controlled manner and enhance host fitness .”
“For instance, this work suggests that we could engineer gut bacteria to secrete more colanic acid to combat age-related health issues,” agreed co-corresponding author Dr Jeffrey Tabor, associate professor of bioengineering and biosciences at Rice University. “Researchers also can use this optogenetic method to unravel other mechanisms by which microbial metabolism drives host physiological changes and influences health and disease .”
Later this week we’ll be reviewing Thryve, a gut health programme that includes both personalised probiotics and microbiome testing – stay tuned!