Fecal Microbiota Transplant as a Treatment for Neurodegenerative Conditions

It is thought that an appreciable fraction of the chronic inflammation of aging is caused by changes in the gut microbiome. There is a bidirectional interaction between the immune system and the microbial populations of the intestinal tract. The immune system gardens these populations, destroying problematic microbes. Microbes secrete metabolites and other molecules that can either benefit or harm the function of the immune system, the harms caused particularly by those microbes capable of provoking a sustained inflammatory response. The immune system declines with age for a range of reasons, and reduced efficacy in immune surveillance of gut microbes allows harmful microbial populations to grow in number, in turn further degrading immune function by inducing a state of chronic inflammation.

Many of the common, ultimately fatal age-related conditions are driven by chronic inflammation and the resulting disruption of normal tissue function. This is very much the case for neurodegenerative conditions. Inflammation in the brain is a prominent feature of tauopathies such as Alzheimer's disease, for example, in which toxic aggregates of altered tau protein form and spread in parallel with the inflammation of brain tissue. Researchers have shown that removing pro-inflammatory senescent cells from the brain, using senolytic drugs, reverses pathology in animal models of tauopathy. How much of inflammation in the brain is the result of senescent cells versus the gut microbiome versus other causes? The only way to find out is to remove each potential cause individually and observe the outcome.

In the case of the gut microbiome, strategies exist to reverse age-related changes. Fecal microbiota transplantation from young individuals to old individuals is the most studied of these approaches, well proven in animal models to reset the balance of microbial populations, reduce inflammation, and improve health. It is already used in humans to tackle cases in which pathological bacteria take over the intestines, and thus, given the will and the funding, it would be a comparatively short path to deploy fecal microbiota transplantation in clinical trials involving patients with inflammatory neurodegenerative conditions.

Fecal Microbiota Transplantation: A Microbiome Modulation Technique for Alzheimer's Disease

The gut microbiota plays a key role in modulating the gut-brain axis, which is a bidirectional communication network that involves the central nervous system, the autonomic nervous system (sympathetic and parasympathetic branches), the enteric nervous system, and the hypothalamic-pituitary-adrenal axis. Recent advances have revealed that the microbiota of the human gut has numerous beneficial functions, such as immune system development, resistance to pathogens, vitamin synthesis, production of metabolites such as short-chain fatty acids (SCFAs), nutrient and drug metabolism, and maintenance of the structural integrity of the intestinal mucosal barrier.

In humans, dysbiosis and changes in gut microbiome composition have been found to contribute to inflammatory bowel disease, type 2 diabetes, metabolic syndrome, obesity, colorectal cancer, Alzheimer's disease (AD), and numerous other diseases. AD is a disastrous neurological disorder affecting 5.8 million Americans (aged 65 years or older) in 2020. AD was the sixth most common cause of death in 2017, accounting for 121,404 deaths in the United States, and the fifth most common cause of death among elderly Americans (65+ years). The sizeable economic burden of AD, as well as its growing prevalence, are leading researchers to look for preventive or disease-modifying treatments.

There are various gut microbiota modulation interventions such as diet modification, prebiotics, probiotics, synbiotics, or fecal microbiota transplantation (FMT). FMT includes the transplantation of the gut microbiota from a donor to a recipient to refurbish the intestinal microflora of the recipient. It has been proven to be a successful treatment for recurrent Clostridium difficile infections. In this review, we summarize the procedure of FMT and its application in the treatment of various neurological disorders with a special emphasis on AD.

Comments

Please post if a significant US or Euro university ever does a study on fecal microbiota

Posted by: JohnD at September 3rd, 2021 7:38 PM

I wonder how much the problem of pathological gut bacteria could be fixed by simply taking an appropriate antibiotic, followed in a couple of days by drinking a few quarts of kefir milk.

Posted by: John G. Cramer at September 4th, 2021 9:33 AM

After the overwhelming success of young blood transfusions which produced as of yet exactly zero old to young transformations, now young shit transplants. What's next? Eat the young? Would also solve climate change, over population, food crisis and if you're a picky eater even race conflict... all at once.

Posted by: Jones at September 4th, 2021 11:16 AM

@Jones
You have to eat the young...shit

Sorry couldn't resist.

On a more serious note, I would say that older bowels promote pro inflammatory bacteria which in turn are harmful in various ways. So gut bacteria transplant might help a bit but don't expect something big except in some edge cases

Posted by: Cuberat at September 4th, 2021 7:07 PM

I was alerted to this post by Daniel of the Cryonics Underground Podcast. He was apparently at a conference where you mentioned this topic.

I'm the creator of HumanMicrobiome.info and HumanMicrobes.org. I'm also a cryonicist. I believe the importance of FMT and the gut microbiome extends far beyond what is mentioned here, and I've been trying to inform people and get them involved for the past decade.

As you mention, the gut microbiome and FMT are indicated in all the diseases of old age, as well as aging itself. In addition, I see it as a possible way to address both the quality of the future society that cryonicists find themselves woken up in, as well as the likelihood that they do get woken up in the future (vs societal collapse, worsening dystopia, etc.). I have gone into more detail on my blog: https://maximiliankohler.blogspot.com/p/blog-page.html

In summary, I view our current society as an extreme dystopia. The exponential increase in chronic disease has caused our current society to resemble Idiocracy. And the evidence suggests that various assaults to our gut microbiomes (vast overuse/abuse of antibiotics, junk diets, lack of breastfeeding, overuse of c-sections, etc.) is a primary factor. I hope that by addressing the gut microbiome with FMT, we can start to reverse this trend.

The major issue is that high quality donors are extremely rare. And despite all my efforts trying to inform people and get them involved in acquiring high quality donors, I still haven't found one, despite screening over 24,000 donor applicants. I would very much appreciate any assistance.

Posted by: Michael Harrop at March 9th, 2022 5:57 PM

I believe Michael Harrop's Human Microbes Org. poop selling operation is not registered, nor approved by FDA. Mr. Harrop claims to be "The Head of Operations" of Human Microbes Organization. He has no certified lab, nor facilities to properly evaluate the product. Mr. Harrop's Human Microbes Org. operates from a mail box rented at a mail box rental store in Riverside, CA. The poop is of uncertain origin, unlikely to be tested and certified by a medical facility lab. Patients considering buying this fecal product should discuss it with their physicians first. If they have any doubts, questions, or adverse product reaction they should check with the FDA, or with their local Health Department.

Posted by: Bryan at May 10th, 2022 12:53 PM
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