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The microbiome is the collection of all bacterial cells that reside within and on us humans. It’s so integral to our overall health and development that it’s often referred to as an organ. Just like a kidney or liver can be diseased, so too can the microbiota. A ‘diseased’ microbiome, also termed dysbiosis, is associated with obesity and impaired immunity.
Also like a diseased liver or kidney, the microbiome can be transplanted from one person to another with remarkable results. Microbial transplants are a common practice and are successful at treating, even reversing, a number of diseases and health issues.
In this post, we’ll discuss the frontier of fecal microbial transplants – what they are, how they work, and why someone would do this. Then we’ll briefly discuss how you can help cultivate a robust and healthy gut microbiome without having to be the recipient.
A fecal microbial transplant (FMT) is the process whereby a bacterial sample from a recipient is harvested and transplanted into a donor. More technically, a stool sample is provided. This is purified and the bacteria are preserved. A donor takes the sample and the transplant is complete.
There are several methods to conduct FMT, including enema, colonoscopy, nasogastric tube, and oral capsules1.
FMT’s are still considered experimental, but they are used under certain circumstances, such as treating infections. There are other, less common, applications, which we’ll discuss below.
Now we’ll provide specific examples of how FMT’s are being used to influence health outcomes and disease recovery.
Microbial transplants are generally used in hospital settings to treat emergent bacterial infections, usually caused by Clostridium Difficile(C. Diff)2. Pre-operation antibiotics wipe out a patient’s microbiome, and often the wrong bacteria are introduced immediately after surgery – in this case C. Diff.
Without a flourishing microbiota, C. Diff can outrun the immune system quickly, and antibiotic treatments are ineffective. FMT’s – though still experimental – have been used to quickly and effectively treat C. Diff infections. FMT’s help to re-establish a patient’s microbiome, which can then outcompete C. Diff for food and space, and eventually clear it.
A healthy microbiome helps to regulate the immune system by keeping pathogenic bacteria at bay and helping to ‘direct’ immune cells to unwanted bacteria3. This is an overly simplistic view, but to be sure, gut microbiome directly influences the development and efficacy of the human immune system, from birth and on.
The human microbiome emerges at birth when the newborn is coated with bacteria on its exodus from the womb. A mother’s breastmilk further enables the microbiome’s development by providing pre-biotics that feed the gut bacteria. The baby’s gut bacteria stimulate the growth of the gut immune system by presenting it with bacterial samples, as well as tempering various immune responses4.
A newborn’s immune system continues to grow this way for its first couple years and is highly sensitive to changes in the gut microbiome – even premature introduction of solid foods can have negative effects.
Eventually the gut microbiome – and the gut immune system – stabilize indefinitely. But this relationship has lasting effects on immune function: prolonged gut dysbiosis can lead to or aggravate conditions such as enteropathy, or inflammation of the intestinal cells. Obesity, Crohn’s, ulcerative colitis, and other auto-immune diseases have roots in altered gut microbial structure4.
FMT’s have been successful at reducing inflammation associated with auto-immune diseases by altering the composition of the microbiome2. The ‘new’ microbiota contains bacteria that help reduce infections from pathogenic species, as well as toning down over-active inflammatory responses.
Inflammatory bowel disease (IBD) is an inflammatory disease that includes ulcerative colitis (UC) and Crohn’s disease2. Both are characterized by chronic inflammation and enteropathy (intestinal cell degradation). They are exceedingly painful and impair quality of life, and while there are a handful of treatments, there is no cure for IBD.
The main suspect in IBD is a defective gut mucosal barrier which leads to chronic infections and over-active inflammatory cells in the gut lining. Gut dysbiosis is also thought to play a role, as reduced microbial diversity (especially low numbers of Bacteroides) has been associated with impaired intestinal and immune system development and IBD severity2,5,6.
FMT’s have been used to treat IBD successfully. While the mechanism isn’t entirely clear, the increase in bacterial diversity enables the gut microbiome to flourish and restore the gut mucosal lining. Furthermore, certain bacteria produce short chain fatty acids (SCFA) that directly reduce local inflammation by stimulating certain immune cells6. Bacteria can also help regulate T-helper cells and cytokine production, which are the on and off switches of inflammation.
Probiotics have also been shown to help reduce symptoms of IBD. Probiotics are live bacterial cultures found in foods like yogurt. These probiotics can help increase the numbers of beneficial bacteria, much like an FMT, and reduce inflammation.
The prevalence of obesity in the U.S. is ~43% as of 20187. It is associated with or directly causes diabetes, heart disease, and stroke. And yet in many cases, it is almost entirely preventable.
The main causes of obesity and diabetes are poor diet and lack of exercise, also genetics. It’s also been thought that gut dysbiosis contributes to obesity and weight gain and prevents people from successfully losing weight. In fact, obese individuals have an altered gut microbiome compared to healthy people. What’s more, you can transmit this “obesity microbiome” into lean recipients and they will gain weight8.
This microbiome transmission works the other way too – FMT’s from healthy adults into obese adults have been shown to result in substantial weight loss, even restored insulin sensitivity in those with diabetes9.
A healthy microbiota can promote weight loss in all body types trough some pretty remarkable mechanisms. A ‘healthy’ microbiome will have a greater capacity to break down indigestible fibers which aids in improved blood glucose handling and the production of SFCA’s like butyrate. These SFCA’s can reduce inflammation and feed other beneficial bacteria which increases overall bacterial diversity. This further reduces inflammation and strengthens the gut barrier.
All this has been shown to promote weight loss in overweight individuals independent of diet and exercise10.
Perhaps the most remarkable potential for FMT’s is slowed ageing. As we’ve seen, the gut microbiome can be altered by changes to diet and other factors. But the microbiome itself changes over time as the bod ages, just like any other organ.
An aging microbiome may actually contribute to age-related decline in humans including poor digestion and even memory11. Knowing this, it may be possible to reverse the signs of aging with – you guessed it – FMT.
Although highly experimental, FMT’s may reduce age-related vision impairments and gut dysbiosis, as well as general inflammatory processes that occur as we age12. This is remarkable, but no one is certain how long these effects may last, or what other beneficial effects we might expect to see.
This certainly isn’t the way I envisioned the Fountain of Youth, but it serves to highlight how important our microbiomes really are.
In addition to the diseases and health conditions indicated above, FMT’s may reduce severity or duration of a handful of other diseases. FMT’s have been used to manage the symptoms and progression of non-alcoholic fatty liver disease (NAFLD)13. This is interesting because NAFLD often progresses into liver cancer; so, to think that a simple fecal transplant could have anti-cancer properties is remarkable.
The list goes on: bone development in kids, insomnia, multiple sclerosis, and colon cancer have all been treated with FMT’s with some success14.
These are all experimental treatments, so we aren’t able to get a prescription or referral for an FMT just yet. But these are active areas of research, so there’s a good chance they’ll become more common as we learn more.
While an FMT certainly is no surgery, it does require a bit of maintenance to ensure the transplanted bacteria continue to thrive. You may want to consider prebiotics like human milk oligosaccharides (HMO) to feed your new bacteria and keep them happy in your gut. HMO and other prebiotics are the preferred diet of our gut microbes.
The human gut microbiome never ceases to amaze. It wasn’t long ago that we regarded our gut bacteria as nothing special. However, the benefits and potential of probiotics and the gut microbiome have been known for quite some time – the early immunologist Eli Metchnikoff was one of the first to pronounce that probiotics could keep us healthy and even delay senility of aging15. Probiotics and prebiotics, like human milk oligosaccharides, are now a fairly standard way to nourish the gut and promote overall health and wellness.
We’ve come a long way and have even further to go in our quest to understand what influences human health, and it seems the microbiota may be the final frontier.
Written By:
Zach Pierce
Masters in Nutritional Biology (with emphasis in Immunology)
Certified Personal Trainer
References:
(1) Fecal Microbiota Transplant (FMT). https://www.childrenshospital.org/treatments/fmt (accessed 2022-05-05).
(2) Gupta, S.; Allen-Vercoe, E.; Petrof, E. O. Fecal Microbiota Transplantation: In Perspective. Ther. Adv. Gastroenterol. 2016, 9 (2), 229–239. https://doi.org/10.1177/1756283X15607414.
(3) Kau, A. L.; Ahern, P. P.; Griffin, N. W.; Goodman, A. L.; Gordon, J. I. Human Nutrition, the Gut Microbiome and the Immune System. Nature 2011, 474 (7351), 327–336. https://doi.org/10.1038/nature10213.
(4) Sekirov, I.; Russell, S. L.; Antunes, L. C. M.; Finlay, B. B. Gut Microbiota in Health and Disease. Physiol. Rev. 2010, 90 (3), 859–904. https://doi.org/10.1152/physrev.00045.2009.
(5) Lopez, J.; Grinspan, A. Fecal Microbiota Transplantation for Inflammatory Bowel Disease. Gastroenterol. Hepatol. 2016, 12 (6), 374–379.
(6) Shen, Z.-H.; Zhu, C.-X.; Quan, Y.-S.; Yang, Z.-Y.; Wu, S.; Luo, W.-W.; Tan, B.; Wang, X.-Y. Relationship between Intestinal Microbiota and Ulcerative Colitis: Mechanisms and Clinical Application of Probiotics and Fecal Microbiota Transplantation. World J. Gastroenterol. 2018, 24 (1), 5–14. https://doi.org/10.3748/wjg.v24.i1.5.
(7) CDC. Obesity is a Common, Serious, and Costly Disease. Centers for Disease Control and Prevention. https://www.cdc.gov/obesity/data/adult.html (accessed 2022-01-08).
(8) Turnbaugh, P. J.; Ley, R. E.; Mahowald, M. A.; Magrini, V.; Mardis, E. R.; Gordon, J. I. An Obesity-Associated Gut Microbiome with Increased Capacity for Energy Harvest. Nature 2006, 444 (7122), 1027–1031. https://doi.org/10.1038/nature05414.
(9) Gomes, A. C.; Hoffmann, C.; Mota, J. F. The Human Gut Microbiota: Metabolism and Perspective in Obesity. Gut Microbes 2018, 9 (4), 308–325. https://doi.org/10.1080/19490976.2018.1465157.
(10) Napolitano, M.; Covasa, M. Microbiota Transplant in the Treatment of Obesity and Diabetes: Current and Future Perspectives. Front. Microbiol. 2020, 11, 590370. https://doi.org/10.3389/fmicb.2020.590370.
(11) Fecal transplants reverse hallmarks of aging. ScienceDaily. https://www.sciencedaily.com/releases/2022/05/220504082622.htm (accessed 2022-05-06).
(12) Parker, A.; Romano, S.; Ansorge, R.; Aboelnour, A.; Le Gall, G.; Savva, G. M.; Pontifex, M. G.; Telatin, A.; Baker, D.; Jones, E.; Vauzour, D.; Rudder, S.; Blackshaw, L. A.; Jeffery, G.; Carding, S. R. Fecal Microbiota Transfer between Young and Aged Mice Reverses Hallmarks of the Aging Gut, Eye, and Brain. Microbiome 2022, 10 (1), 68. https://doi.org/10.1186/s40168-022-01243-w.
(13) Delaune, V.; Orci, L. A.; Lacotte, S.; Peloso, A.; Schrenzel, J.; Lazarevic, V.; Toso, C. Fecal Microbiota Transplantation: A Promising Strategy in Preventing the Progression of Non-Alcoholic Steatohepatitis and Improving the Anti-Cancer Immune Response. Expert Opin. Biol. Ther. 2018, 18 (10), 1061–1071. https://doi.org/10.1080/14712598.2018.1518424.
(14) Smits, L. P.; Bouter, K. E. C.; de Vos, W. M.; Borody, T. J.; Nieuwdorp, M. Therapeutic Potential of Fecal Microbiota Transplantation. Gastroenterology 2013, 145 (5), 946–953. https://doi.org/10.1053/j.gastro.2013.08.058.
(15) Mackowiak, P. Recycling Metchnikoff: Probiotics, the Intestinal Microbiome and the Quest for Long Life. Front. Public Health 2013, 1.
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