New Ideas in Science
One of the most exciting aspects of science is the discovery and development of new ideas and insights that lead to new ways of understanding and manipulating the natural world. Theories that seem preposterous at first can turn out to revolutionize medicine and other science-based fields.
Sometimes, these theories are greeted with skepticism but eventually prove themselves. The idea that living organisms too small to see exist and can cause disease took centuries to catch on and be empirically validated, but it has led to many of the most dramatic successes in medicine, such as immunization, antibiotics, and doctors washing their hands between patients. The concept that gastric ulcers could be caused by a bacterial infection was greeted with great skepticism in the 1980s, but the first proponents of the idea were awarded the Nobel Prize for their work in 2005.1
Unfortunately, it also happens that some new ideas in medicine are adopted with great enthusiasm and put into practice only to prove dangerously mistaken. The treatment of mental illness by deliberate surgical damage to the frontal lobe (aka lobotomy) also overcame initial skepticism and led to a Nobel Prize. The procedure became common and was performed on tens of thousands of patients. It is now widely recognized as one of the greatest clinical and ethical failures in modern medicine.2
More recently, the idea that many diseases, and even normal aging, were caused by oxidative damage and that antioxidant supplements could prevent disease or retard aging was proposed in the 1990s and initially supported by laboratory and observational studies. To this day, marketing for human and pet foods often includes health claims for “powerful antioxidant” supplements and “superfoods” based on this hypothesis. Sadly, the early promise of this idea has not been fulfilled in real-world studies, which have found few benefits and unexpected dangers in the use of antioxidant supplements.3–11
It is impossible to know in advance which ideas in science will lead to great benefits and which will prove mistaken and lead to equally great harm. Knowing this, a rational strategy would be to approach promising new hypotheses cautiously. A careful, stepwise evaluation from in vitro research through high-quality clinical studies and systematic reviews should be undertaken before we enthusiastically employ new ideas or methods in clinical patients.
Such a cautious approach, unfortunately, often does not suit the human temperament or the psychological and economic incentives to turn hypotheses into therapies and products. In this column, I have written about promising veterinary treatments that have been embraced well in advance of reliable evidence for their benefits, from cannabis12,13 to cold laser14, probiotics15 to electromagnetic field therapies,16 and there are many others. Whether each of these will prove the next antibiotic or the next lobotomy remains to be seen, but the regulatory, economic, and cultural features of veterinary medicine seem to consistently encourage early adoption rather than a cautious, evidence-based approach.
The Microbiome
The latest example of a promising idea that is being turned into clinical tests and therapies well before this is justified by scientific evidence is the concept of the microbiome.17,18 The recognition that microorganisms can be beneficial, even necessary for a healthy organism is a legitimately revolutionary and exciting idea. While it is an exaggeration to say we each carry around more microbial than human cells,19,20 there is no doubt we harbor a complex ecosystem of bacterial, viruses, and fungi that influences our health.18
The very complexity of this system is one of the major reasons simplistic concepts of “good bacteria” and “bad bacteria” or of “balancing” the system with diet changes or supplements are unlikely to be fruitful. We have only begun to even identify the myriad organisms humans and our animal companions carry on and within us, and we have little idea what they are up to. Even crude taxonomic assessments of the microbiome reveal tremendous variation with age, geographic population, diet, and innumerable individual factors. We have a lot of work to do just understanding the composition and activity our microbiomes before we can hope to engineer them to prevent or treat disease.
Fecal Microbiome Testing
Despite this, there is currently a plethora of products in human and veterinary medicine purporting to do just that. Companies such as Nom Nom Now21 and Animal Biome22 offer fecal microbiome testing for pets to “provide insight into their gut health,”22 “improve your pets’ gut and overall health,”22 and “to provide you with real insights on their unique needs [so] you can have the confidence you’re making the best choices to provide them a happy, healthy life.”21
These companies, not surprisingly, offer supplements, diets, and even fecal microbiome transplantation purportedly guided by the analysis they conduct.
In reality, there is no reliable research evidence showing that these tests provide accurate, actionable information about health or that they can be used to effectively guide dietary or healthcare choices. We lack not only clinical studies validating these specific marketing claims, but even the basic understanding of the determinants of an individual’s microbial ecology and the relationship of this to health and disease.
A few descriptive studies have provided information about the types of bacteria (other microbes are not routinely identified or studied) present in healthy dogs and cats.23 Other studies have compared the microbiota of individuals on different diets (e.g. cooked or raw, hydrolyzed)24–26 or evaluated the bacterial ecology of individuals with specific health conditions (e.g. IBD and acute or chronic diarrhea, obesity, etc.)27–30.
A Canine Dysbiosis Index (DI) has been developed which characterizes differences in fecal microbial organisms between healthy dogs and those with chronic enteropathies.31,32 Though this may eventually be clinically useful, the authors caution, “future studies will need to evaluate the clinical utility of the DI as an assessment tool for microbiota dysbiosis associated with CEs, and the usefulness of tracking microbiota over time and in response to treatment…microbiota is just one of several factors in the pathogenesis of the disease [and there is] overlap in the DI seen between healthy and diseased dogs.”31
These are all important preliminary steps towards a comprehensive and useful understanding of the microbiome, but they do not validate the claims often made for commercial fecal microbiome testing or treatment recommendations based on these tests.
The available research into the human microbiome is much more extensive than what is available for veterinary species. Here is what reviews of that evidence conclude:
The functionality of these microbial communities cannot be easily reduced to a simple summation of potential beneficial and harmful activities…While the premise behind individual microbiome testing is to inform personalized diagnosis and therapies, the current body of knowledge is not sufficient to allow for meaningful diagnoses…irrespective of what a company puts in their marketing material.33
“We are at the very beginning of understanding what one’s microbiome profile means for their susceptibility to or progression of disease…There are far more unknowns than knowns regarding the role of the microbiome and human health.”33
“Mechanistic links of specific changes in gut microbiome structure with function or markers of human health are not yet established; it is not established if dysbiosis is a cause, consequence, or both of changes in human gut epithelial function and disease.”34
Caveat Emptor
While enthusiasm for new discoveries and hypotheses is a necessary part of scientific progress, the premature application of these to clinical patients can be harmful. Treatments based on fecal microbiome testing cannot be reliable when testing methods have not be validated and standardized and the clinical research showing clinical utility hasn’t yet been done. Rolling the dice on promising but unproven new ideas sometimes work out well, but the odds are greater that we will fail to help or even harm our patients if we take shortcuts in the scientific road to understanding.
References
1. Marshall B. A Brief History of the Discovery of Helicobacter pylori. In: Suzuki H, Warren R, Marshall B, eds. A Brief History of the Discovery of Helicobacter Pylori. Tokyo: Springer; 2016.
2. Gallen M. A brief reflection on the not-so-brief history of the lobotomy | British Columbia Medical Journal. BC Med J. 2017;59(6):302-304. https://www.bcmj.org/mds-be/brief-reflection-not-so-brief-history-lobotomy. Accessed February 17, 2020.
3. Yee C, Yang W, Hekimi S. The intrinsic apoptosis pathway mediates the pro-longevity response to mitochondrial ROS in C. elegans. Cell. 2014;157(4):897-909. doi:10.1016/j.cell.2014.02.055
4. Pizzino G, Irrera N, Cucinotta M, et al. Oxidative Stress: Harms and Benefits for Human Health. Oxid Med Cell Longev. 2017;2017:8416763. doi:10.1155/2017/8416763
5. Schürks M, Glynn RJ, Rist PM, Tzourio C, Kurth T. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ. 2010;341:c5702. doi:10.1136/BMJ.C5702
6. Moyer MW. The Myth of Antioxidants. Sci Am. 2013;308(2):62-67. doi:10.1038/scientificamerican0213-62
7. Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and health. Int J Biomed Sci. 2008;4(2):89-96. http://www.ncbi.nlm.nih.gov/pubmed/23675073. Accessed December 11, 2018.
8. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention. JAMA. 2007;297(8):842. doi:10.1001/jama.297.8.842
9. Bjelakovic G, Nikolova D, Gluud C. Antioxidant supplements and mortality. Curr Opin Clin Nutr Metab Care. 2013;17(1):1. doi:10.1097/MCO.0000000000000009
10. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. In: Bjelakovic G, ed. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd; 2008:CD007176. doi:10.1002/14651858.CD007176
11. Paulsen G, Cumming KT, Holden G, et al. Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial. J Physiol. 2014;592(8):1887-1901. doi:10.1113/jphysiol.2013.267419
12. McKenzie BA. Cannabis-based remebdies: No reliable clinical research evidence. Vet Pract News. August 2017:38.
13. McKenzie B. A conclusion on cannabis? Vet Pract News. July 2019:26-27.
14. McKenzie BA. Uses, Evidence, and Safety of Laser Therapy. Vet Pract News. August 2018:32-33.
15. McKenzie BA. Probiotics and today’s pets. Vet Pract News. January 2018:30-31.
16. McKenzie B. Do pulsed electromagnetic field devices offer any benefit? Vet Pract News. January 2020:30-31.
17. Allaband C, McDonald D, Vázquez-Baeza Y, et al. Microbiome 101: Studying, Analyzing, and Interpreting Gut Microbiome Data for Clinicians. Clin Gastroenterol Hepatol. 2019;17(2):218-230. doi:10.1016/j.cgh.2018.09.017
18. Knight R, Callewaert C, Marotz C, et al. The Microbiome and Human Biology. Annu Rev Genomics Hum Genet. 2017;18:65-86. doi:10.1146/annurev-genom-083115-022438
19. Sender R, Fuchs S, Milo R. Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans. Cell. 2016;164(3):337-340. doi:10.1016/j.cell.2016.01.013
20. Sender R, Fuchs S, Milo R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLOS Biol. 2016;14(8):e1002533. doi:10.1371/journal.pbio.1002533
21. NomNomNow Microbiome – Everybody poops. https://www.nomnomnow.com/site/products/microbiome/. Published 2018. Accessed February 17, 2020.
22. Microbiome Products Restore Pet Gut Health | AnimalBiome. https://www.animalbiome.com/how-it-works. Published 2019. Accessed February 17, 2020.
23. Deng P, Swanson KS. Gut microbiota of humans, dogs and cats: current knowledge and future opportunities and challenges. Br J Nutr. 2015;113 Suppl:S6-17. doi:10.1017/S0007114514002943
24. JS S, E O, JB H, et al. Effects of a hydrolyzed protein diet and metronidazole on the fecal microbiome and metabolome in healthy dogs. J Vet Intern Med. 2016;30(4):1455.
25. Schmidt M, Unterer S, Suchodolski JS, et al. The fecal microbiome and metabolome differs between dogs fed Bones and Raw Food (BARF) diets and dogs fed commercial diets. Loor JJ, ed. PLoS One. 2018;13(8):e0201279. doi:10.1371/journal.pone.0201279
26. Sandri M, Dal Monego S, Conte G, Sgorlon S, Stefanon B. Raw meat based diet influences faecal microbiome and end products of fermentation in healthy dogs. BMC Vet Res. 2016;13(1):65. doi:10.1186/s12917-017-0981-z
27. Handl S, German AJ, Holden SL, et al. Faecal microbiota in lean and obese dogs. FEMS Microbiol Ecol. 2013;84(2):332-343. doi:10.1111/1574-6941.12067
28. Minamoto Y, Otoni CC, Steelman SM, et al. Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease. Gut Microbes. 2015;6(1):33-47. doi:10.1080/19490976.2014.997612
29. Kalenyak K, Isaiah A, Heilmann RM, Suchodolski JS, Burgener IA. Comparison of the intestinal mucosal microbiota in dogs diagnosed with idiopathic inflammatory bowel disease and dogs with food-responsive diarrhea before and after treatment. FEMS Microbiol Ecol. 2018;94(2). doi:10.1093/femsec/fix173
30. Suchodolski JS, Markel ME, Garcia-Mazcorro JF, et al. The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease. PLoS One. 2012;7(12):e51907. doi:10.1371/journal.pone.0051907
31. AlShawaqfeh MK, Wajid B, Minamoto Y, et al. A dysbiosis index to assess microbial changes in fecal samples of dogs with chronic inflammatory enteropathy. FEMS Microbiol Ecol. 2017;93(11). doi:10.1093/femsec/fix136
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34. McBurney MI, Davis C, Fraser CM, et al. Establishing What Constitutes a Healthy Human Gut Microbiome: State of the Science, Regulatory Considerations, and Future Directions. J Nutr. 2019;149(11):1882-1895. doi:10.1093/jn/nxz154
Good article.
I’ve often wondered if my dogs’ love of cat feces and various other disgusting things has something to do with enhancing gut flora. But I don’t expect to see research on that any time soon 🙂
There’s so much we don’t know.
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I think there’s at least some room for things like FMT (fecal microbiota transplant). It’s approved for chronic, treatment resistant c diff in humans and is effective when just vancomycin isn’t enough, and trials around FMT and IBD seem to be showing some benefit (I’m admittedly biased as an IBD patient myself, I’m running low on treatment options and a poop transplant is far better than a colectomy, and I know animals with IBD don’t have the same extent of options, there’s no ileostomies for dogs or humira for cats).
I do think there’s a potential pathway to better options for things like IBD than a life bouncing on and off corticosteroids though understanding of fecal microbiota, or maybe treating a chronic intestinal infection, as in human c diff. But we still don’t know enough to say much of anything from a commercial test, and specific foods and supplements are not the same thing as FMT and it seems like just a way to tag on to the probiotic and pet food craze and sap wallets of people who are trying to keep their pets healthy.
Next thing you know they’ll have you send in anal gland secretions and they’ll tell you why your dogs have socialization problems.
I could almost see a viable option for commercial fecal testing for GI parasites and then suggesting appropriate dewormers, but these tests suggest we know what the “right” gut microbiome looks like, and that is something we do not know and it’s unlikely there’s a single “best” gut microbiome anyways.
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The key here is that these could be useful therapies, but we haven’t yet shown hat they are or how to use them. The problem with them is not that we know they don’t work, only that so far we don’t know that they do, and until we have that evidence, we are quite possible wasting our patients’ time or even doing harm.
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I say this sincerely, and as a scientist; I see a lot of valid skeptism on your site, but not a lot of suggested alternatives.
I have a dog with severe, non-responsive IBD. I’ve tried everything the vet suggested and even gone through pubmed I don’t know how many times trying out any viable solutions (such as supplementing with beta glucans that showed promise in a clinical trial with n of 41) nothing has worked.
Do you have any suggestions on what does work?
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I’m sorry you are having a tough time with your dog, but I think you are misconstruing the purpose of this site. I am not providing a comprehensive review of all therapies for specific medical problems or solutions for individual cases, which no one can legitimately do on the internet. I review the evidence for specific hypotheses, particularly those that are aggressively promoted without good evidence. This helps people to make informed decisions, but no web site is going to provide all the answers for all individuals.
The most appropriate thing to do is what you have done, which is work with individual veterinarians who use the best available evidence to formulate strategies for helping your dog. For difficulty cases, a board-certified internal medicine specialist is likely appropriate. There are reviews of available therapies for IBD and the associated evidence, but nothing is going to substitute for a consistent relationship with a personal veterinarian.
Of course, the difficult part is that there is not going to be a perfect solution for every patient because our knowledge is always limited and imperfect. Pseudoscience thrives on the margins because people are desperate for cures when science-based medicine is not meeting their needs. This is understandable, but the desire for these solutions, and the fact that people claim to have them without proving those claims, doesn’t make the solutions real. I don’t know what might or might not help your dog, all I can do is offer information on specific therapies, which will be useful to some but not to everyone.
Good luck!
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Has there been any update to this research?
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There have been more studies attempting to identify the variety of organisms present in the canine GI tract, but nothing clinical showing that testing is useful in diagnosis or guiding treatment of disease.
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