A growing pile of proof indicates that the tens of trillions of microorganisms that usually live in our intestines– the so-called gut microbiome– have far-reaching impacts on how our bodies function. Now, a brand-new study suggests that the gut microbiome likewise plays a crucial role in the health of our brains, according to researchers from Washington University School of Medicine in St. Louis.
To identify whether the gut microbiome may be playing a causal role, the scientists changed the gut microbiomes of mice predisposed to develop Alzheimers- like brain damage and cognitive disability. When such mice were raised under normal, nonsterile conditions, they established regular microbiomes. A course of antibiotics at 2 weeks of age, however, completely altered the structure of germs in their microbiomes.
Proof is accumulating that the gut microbiomes in individuals with Alzheimers disease can vary from those of healthy people. But it isnt clear whether these distinctions are the cause or the outcome of the disease– or both– and what impact altering the microbiome might have on the course of the disease.
To figure out whether the gut microbiome might be playing a causal role, the researchers altered the gut microbiomes of mice predisposed to establish Alzheimers- like brain damage and cognitive impairment. The mice were genetically customized to express a mutant type of the human brain protein tau, which develops up and triggers damage to neurons and atrophy of their brains by 9 months of age.
In addition to Holtzman, the research study team consisted of gut microbiome professional and co-author Jeffrey I. Gordon, MD, the Dr. Robert J. Glaser Distinguished University Professor and director of the Edison Family Center for Genome Sciences & & Systems Biology; first author Dong-Oh Seo, PhD, a trainer in neurology; and co-author Sangram S. Sisodia, PhD, a teacher of neurobiology at the University of Chicago.
When such genetically customized mice were raised under sterilized conditions from birth, they did not get gut microbiomes, and their brains revealed much less damage at 40 weeks of age than the brains of mice harboring typical mouse microbiomes.
When such mice were raised under typical, nonsterile conditions, they developed normal microbiomes. A course of antibiotics at 2 weeks of age, however, completely changed the composition of germs in their microbiomes.
” We currently know, from studies of brain growths, normal brain development, and related subjects, that immune cells in male and female brains react extremely in a different way to stimuli,” Holtzman stated. “So its not extremely surprising that when we manipulated the microbiome we saw a sex distinction in reaction, although it is hard to say what precisely this indicates for males and females living with Alzheimers illness and related disorders.”
More experiments connected 3 particular short-chain fatty acids– compounds produced by particular kinds of gut germs as items of their metabolic process– to neurodegeneration. All 3 of these fatty acids were limited in mice with gut microbiomes modified by antibiotic treatment, and undetectable in mice without gut microbiomes.
These short-chain fats appeared to trigger neurodegeneration by activating immune cells in the blood stream, which in turn in some way activated immune cells in the brain to harm brain tissue. When middle-aged mice without microbiomes were fed the 3 short-chain fats, their brain immune cells became more reactive, and their brains showed more indications of tau-linked damage.
” This study may offer crucial insights into how the microbiome influences tau-mediated neurodegeneration, and recommends treatments that change gut microbes might affect the start or development of neurodegenerative conditions,” said Linda McGavern, PhD, program director at the National Institute of Neurological Disorders and Stroke (NINDS), which offered some of the funding for the study.
The findings recommend a brand-new approach to preventing and treating neurodegenerative illness by customizing the gut microbiome with prescription antibiotics, probiotics, specialized diets or other ways.
” What I would like to know is, if you took mice genetically predestined to develop neurodegenerative illness, and you controlled the microbiome prior to the animals start revealing signs of damage, could you avoid or slow neurodegeneration?” Holtzman asked. “That would be the equivalent of beginning treatment in an individual in late midlife who is still cognitively regular but on the edge of developing problems. If we might start a treatment in these types of genetically sensitized adult animal models before neurodegeneration very first emerges, and reveal that it worked, that could be the kind of thing we could check in individuals.”
Reference: “ApoE isoform– and microbiota-dependent progression of neurodegeneration in a mouse design of tauopathy” by Dong-oh Seo, David ODonnell, Nimansha Jain, Jason D. Ulrich, Jasmin Herz, Yuhao Li, Mackenzie Lemieux, Jiye Cheng, Hao Hu, Javier R. Serrano, Xin Bao, Emily Franke, Maria Karlsson, Martin Meier, Su Deng, Chandani Desai, Hemraj Dodiya, Janaki Lelwala-Guruge, Scott A. Handley, Jonathan Kipnis, Sangram S. Sisodia, Jeffrey I. Gordon and David M. Holtzman, 13 January 2023, Science.DOI: 10.1126/ science.add1236.
Funding: Good Ventures Foundation, NIH/National Institute of Neurological Disorders and Stroke.
The gut microbiome, which is the collection of trillions of microorganisms that reside in our intestinal tracts, plays an essential role in the health of our bodies by producing vitamins, assisting us absorb food, preventing the overgrowth of harmful bacteria, and managing the body immune system. A brand-new research study from Washington University School of Medicine suggests that the gut microbiome likewise plays an essential function in the health of our brains.
Findings from research study on mice suggest a brand-new approach to treating Alzheimers and other neurodegenerative illness.
A growing stack of evidence shows that the 10s of trillions of microorganisms that usually live in our intestinal tracts– the so-called gut microbiome– have far-reaching effects on how our bodies function. Members of this microbial community produce vitamins, assist us digest food, avoid the overgrowth of harmful bacteria and regulate the body immune system, amongst other advantages. Now, a new study suggests that the gut microbiome likewise plays a key role in the health of our brains, according to scientists from Washington University School of Medicine in St. Louis.
The study, in mice, discovered that gut bacteria– partly by producing substances such as short-chain fatty acids– affect the behavior of immune cells throughout the body, consisting of ones in the brain that can harm brain tissue and worsen neurodegeneration in conditions such as Alzheimers illness. The findings, published on January 13 in the journal Science, open up the possibility of reshaping the gut microbiome as a way to deal with or prevent neurodegeneration.
” We gave young mice antibiotics for just a week, and we saw a permanent change in their gut microbiomes, their immune responses, and just how much neurodegeneration associated to a protein called tau they experienced with age,” said senior author David M. Holtzman, MD, the Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology. “Whats interesting is that controling the gut microbiome could be a method to have an impact on the brain without putting anything directly into the brain.”