Eyes can gaze at themselves in a mirror and see the only visible part of the brain looking back. The brain can contemplate this concept and enter a surrealistic thought loop—an intellectual infinity mirror of the mind reflecting endlessly on itself. During central nervous system (CNS) development, the optic nerve and retina grow from outpouchings of the primitive brain1 and share functional features with the brain, including similar responses to inflammation and bidirectional communication with the gut.2,3,4 Patients with intestinal disorders such as inflammatory bowel disease are at higher risk of developing inflammatory eye disorders,5,6 and neurodegenerative brain disorders, such as Parkinson’s and Alzheimer’s disease, tend to exhibit early symptoms in the gut and eye.7,8,9,10
Aging increases susceptibility to chronic disease and organ dysfunction. Researchers are discovering connections between the aging gut microbiota and chronic, low-grade inflammation in other organ systems throughout the body—known as inflammaging. In a recent study published in Microbiome, Aimée Parker, a research scientist at the Quadram Institute’s Gut Microbes and Health Research Programme, and her team examined how changes in gut microbial communities influence immune status and age-related inflammation in the mouse gut, brain, and eye.11 “Gut microbes have a really important role in regulating inflammation that's associated with deteriorating brain and eye function in later life,” Parker said. “Ultimately, we might be able to manipulate our gut microbes to help maintain good vision and good brain health in older age.”
Parker’s team transplanted fecal microbiota from young to old mice and vice versa to determine whether swapping gut microbes could reverse or promote signs of inflammaging. They tracked markers of inflammation in the blood, gut, brain, and eye, and found that fecal microbiota transplanted from old to young mice increased intestinal lining permeability and local inflammation, causing detrimental bacterial byproducts to leak into the blood and trigger CNS inflammation. Parker’s team also found that these mice had lower levels of a key protein involved in normal retina function. Providing old mice with a young microbiota improved the barrier function of the gut lining and reduced local and remote inflammation in the brain and eye. “Our most exciting finding, I think, was that in the eye, not only did we reduce some of the age-associated inflammation, but we also restored expression of the protein that is important for normal vision,” Parker said.
Parker’s team corroborated the work of others,12,13 showing that diversifying the aging gut microbiome may extend health span as well as life span. The study also identified candidate microorganisms and the molecular byproducts of their metabolism that may underlie these restorative effects. “We know from other studies that…there are certain types of bacteria in our intestines that metabolize fiber and produce molecules like short-chain fatty acids, butyrate, propionate, and acetate, which are shown to be very beneficial,” said Neil Mabbott, a professor and personal chair in immunopathology at the University of Edinburgh, who was not involved in the current study. “It is quite surprising how just a simple manipulation of the microbiome in the intestine can improve the inflammatory status in the brain and other tissues.”
According to Parker, the eye is a highly vascularized, energy hungry part of the body, making it very sensitive to age-related changes. As an anatomical extension of the brain, it also provides an easily accessible target for diagnostic imaging to observe early signs of CNS disease. As researchers continue to understand the intimate links between inflammaging, the gut microbiota, and CNS, the eyes remain a window to the soul and the brain.
- S. Fuhrmann, “Eye morphogenesis and patterning of the optic vesicle,” Curr Top Dev Biol, 93:61-84, 2010.
- J.L. Floyd, M.B. Grant, “The gut-eye axis: lessons learned from murine models,” Ophthalmol Ther, 9:499-513, 2020.
- G. Agirman et al., “Signaling inflammation across the gut-brain axis,” Science, 374(6571):1087-92, 2021.
- J.F. Cryan et al., “The microbiota-gut-brain axis,” Physiol Rev, 99(4):1877-2013, 2019.
- G. Scuderi et al., “Gut microbiome in retina health: the crucial role of the gut-retina axis,” Front Microbiol, 12:726792, 2022.
- J. Shah et al., “Ocular manifestations of inflammatory bowel disease,” Inflamm Bowel Dis, 27(11):1832-8, 2021.
- M. Sochocka et al., “The gut microbiome alterations and inflammation-driven pathogenesis of Alzheimer’s disease—a critical review,” Mol Neurobiol, 56:1841-51, 2019.
- E. Menozzi et al., “The gut-brain axis and Parkinson disease: clinical and pathogenetic relevance,” Ann Med, 53(1):611-25, 2021.
- S. Fereshetian et al., “Protein and imaging biomarkers in the eye for early detection of Alzheimer’s disease,” J Alzheimers Dis Rep, 5(1):375-87, 2021.
- L. Moons, L. De Groef, “Multimodal retinal imaging to detect and understand Alzheimer's and Parkinson's disease,” Curr Opin Neurobiol, 72:1-7, 2022.
- A. Parker et al., “Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain,” Microbiome, 10(1):68, 2022.
- D.S. Donaldson et al., “Microbial stimulation reverses the age-related decline in M cells in aged mice,” iScience, 23(6):101147, 2020.
- M. Boehme et al., “Microbiota from young mice counteracts selective age-associated behavioral deficits,” Nat Aging, 1:666-76, 2021.