Probiotics: Gastrointestinal Miracle or the Next Essential-Oil Remedy?

Image author: Madeline Chan

Written by: Ibreez Asaria

Figure 1: Mechanistic interactions between probiotics and the host and its microbiome. Source: Suez, J., Zmora, N., Segal, E. et al. The pros, cons, and many unknowns of probiotics. Nature Medicine 2019; 25, 716–729. Available from: 

https://doi.org/10.1038/s41591-019-0439-x

Abstract 

From brewing kombucha tea beverages to regulating neuropeptidergic circuitry in the hypothalamus, bacteria are active players in our day-to-day functioning1. One of the many types of bacteria that has come into the spotlight within the last decade is gut bacteria, otherwise known as the gut flora or gut microbiome. With almost 100 trillion of these microorganisms residing in our digestive systems2, researchers have begun to think of the gut microbiome as “an additional organ system”3 largely because of evidence to support its regulation appetite, mood, and weight, among others. Given these findings, many researchers and pharmaceutical companies have been searching for ways to modify gut bacteria to induce more positive effects. A popular example of this is through probiotics. The World Health Organization (WHO) defines probiotics as “live microorganisms which when administered in adequate amounts confer a health benefit on the host”4. However, cases such as the 2014 death of a preterm infant associated with gastrointestinal mucormycosis5 point to the possibility of harm in certain circumstances. Hence, this article aims to collect and unpack some of the most popular benefits and criticisms of probiotics for the gastrointestinal health of individuals with and without existing conditions. 

Introduction 

One of the earliest identifications of beneficial bacteria was made in 1905 by the Russian zoologist Elie Metchnikoff, who proposed that the increased lifespan of the Bulgarian population was, in part, due to the ingestion of bacteria from the Lactobacillus group, used to make yogurt. These observations were later followed by successful bacteria replenishing trials led by urologist Dr. Andrew Bruce in 1973 for individuals with urinary tract infections (UTIs)6 which soon after coined the term probiotics in 19747

More recently, scientific scholars have turned their attention to the gut-brain axis and whether or not gut bacteria can be altered to positively influence mental or cognitive diseases. As Dr. John Bienenstock, Director of McMaster University’s Brain Body Institute (BBI) points out, “the microbiome complexities, what the bacteria make, the interactions that occur, the multiplicity of pathways involved have been very difficult to chase down“ which makes it difficult to conclusively say that the gut-brain axis can be manipulated successfully.8 However, with new supplements being put on shelves every day, it becomes difficult to see past the novelty that probiotics claim. This is especially the case when considering that the projected valuation of the probiotics supplement industry is USD 75.90 billion by 2026.9 The problem we are faced with here is one of individualized care. It is still unclear how current probiotic supplements will interact in different hosts, and whether or not individuals with existing gut conditions can reap the same benefits as others, without the negative effects. 

Criticisms 

One of the primary concerns around probiotic efficacy is the large variability in research due to the disparity in studied strains. While most studies use dominant microorganisms that belong to both the Lactobacillus and Bifidobacterium genera which have some health-associated mechanisms of action, “other traits may be species- or even strain-specific, or may require interaction between different strains to produce an effect”10. This feeds into the larger issue of how the interactions of probiotics with the indigenous microbiome might be controlled or manipulated, as seen in Table 1. 

Table 1 Source: Suez, J., Zmora, N., Segal, E. et al. The pros, cons, and many unknowns of probiotics. Nature Medicine 2019; 25, 716–729. Available from: https://doi.org/10.1038/s41591-019-0439-x

Short-term health impacts related to this interaction have shown fatal results, especially in neonates and critically-ill elderly patients. The fatal 2014 case of a preterm infant showed the development of gastrointestinal mucormycosis, or fungal infection, after being treated with the probiotic Solgar ABC Dophilus Powder11. Investigations reported the bottle containing the probiotic was contaminated, although it was not concluded how exactly this happened. Another study in 2008 of patients with predicted acute pancreatitis showed that out of 152 patients given probiotics, and 144 given placebo, the number of fatalities was 24 and 9, respectively. While it is easy to suggest the causes of this difference in mortality as probiotic strain type, the study leads back to this idea that the effects of probiotics are not the same for each individual, and should be avoided for certain individuals. 

Long-term health impacts related to these types of interactions were studied in a 2018 report by Suez et al which indicate persistent dysbiosis, or maladaptation of the microbiota. Individuals, after taking antibiotics, who ingested certain probiotic strains showed delays in the reconstitution of both the fecal and the GI mucosal microbiome compared to no intervention12. Two additional trials supported these findings and showed that postantibiotic probiotic administration correlated to decreased quantities of observed bacterial species in the gut microbiome13. The long-term health implications of gut dysbiosis include hampered colonization resistance to pathogens and gut mucosal barrier development14. However, this relationship is also a threat to healthy individuals, who have an increased risk of developing communicable diseases, and potentially, non-communicable diseases such as obesity, idiopathic arthritis, and type 1 or 2 diabetes15

Benefits 

With more research being conducted into mixing strains of bacteria, various meta-analyses have provided different perspectives on treating both adults and children. A strong case for this is in the treatment of acute gastroenteritis. Strains within the Lactobacillus genus have been associated with shortened acute diarrhea in children by approximately 1 day16. In adults, mixtures of bacterial strains also have seen more positive results in improving antibiotic-associated diarrhea17. However, two 2015 studies of 1800 and 4000 children dispute these associative findings when controlling for multiple health centres, which once again leads to the issue of individualized treatment guidelines18

With the continued marketing of “probiotic-rich” foods to adults and children, many have become interested in the development of probiotic therapies. One such potential therapy is fecal microbiota transplantation (FMT). 

Albeit bizarre at first glance, FMT refers to the transfer of healthy microbiota, or “good bacteria” to a recipient via instillation of fecal material19. Over the last decade, this treatment has shown tremendous success with recurrent C. difficile colitis as a result of antibiotic therapy20. However, FMT lacks the sort of precision that specific probiotic strains have to mucosal barrier development, which also make it more susceptible to causing post-operative infections21. Despite this, a 2017 multi-center, double-blind randomized study showed a significant beneficial effect of FMT in “reducing disease activity and prolonging remission” compared to the placebo group22. This study also identified a strain of bacteria in the recipient’s fecal material that correlated with a poorer response of treatment23.

Conclusion 

Given the current lack of strain-specific data on individuals with critical illnesses, a reasonable conclusion would shy away from the use of probiotics for high-risk individuals. Drug manufacturers should continue to strictly follow Health Canada guidelines when making health claims and physicians should proceed with caution and continue to evaluate best practices in gut health. It is also still unclear what long-term health implications can result from a change in bacteria colonization resistance. As someone with Celiac Disease (CeD), the current buzz around probiotics and FMT gives me hope, but it is important that we understand exactly what we are putting into our bodies. On this basis, much is still needed to be learned to reduce the risk to neonates and adults, but until we know more, we can be excited for these “little bursts of light here and there”24

References List 

1. Fetissov, S., 2016. Role of the gut microbiota in host appetite control: bacterial growth to animal feeding behaviour. Nature Reviews Endocrinology, 13(1), pp.11-25. 2. Can gut bacteria improve your health? – Harvard Health. Harvard Medical School. 2020. Available from: https://www.health.harvard.edu/staying-healthy/can-gut-bacteria-improve-your-health 3. Ibid. 

4. Guidelines for the Evaluation of Probiotics in Food [Internet]. London, Ontario: World Health Organization; 2002. Available from: https://www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf

5. Fatal Gastrointestinal Mucormycosis in an Infant Following Use of Contaminated ABC Dophilus Powder From Solgar Inc. | Fungal Diseases | CDC [Internet]. Centres for Disease Control and Prevention. 2020. Available from: https://www.cdc.gov/fungal/outbreaks/rhizopus-investigation.html

6. Puebla-Barragan S, Reid G. Forty-five-year evolution of probiotic therapy. Microbial Cell. 2019;6(4):184-196. Available from: doi: 10.15698/mic2019.04.673

7. Fuller R. (1992) History and development of probiotics. In: Probiotics. Springer, Dordrecht. Available from: https://doi.org/10.1007/978-94-011-2364-8_1

8. Daniells S. Probiota Champions: In conversation with Dr John Bienenstock [Internet]. nutraingredients-usa.com. 2020. Available from: https://www.nutraingredients-usa.com/Article/2020/12/04/Probiota-Champions-In-co nversation-with-Dr-John-Bienenstock 

9. Global Probiotics Market : Industry Type, Size, Share, Trends and Forecast 2019– 2026. Zion Market Research. 2020. Available from: https://www.zionmarketresearch.com/report/probiotics-market

10. Suez, J., Zmora, N., Segal, E. et al. The pros, cons, and many unknowns of probiotics. Nature Medicine 2019; 25, 716–729. Available from: https://doi.org/10.1038/s41591-019-0439-x

11. Vallabhaneni S, Walker TA, Lockhart SR, et al. Notes from the field: Fatal gastrointestinal mucormycosis in a premature infant associated with a contaminated dietary supplement–Connecticut, 2014. MMWR Morb Mortal Wkly Rep. 2015;64(6):155-156. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4584706/

12. Suez, J., Zmora, N., Segal, E. et al. The pros, cons, and many unknowns of probiotics. Nature Medicine 2019; 25, 716–729. Available from: https://doi.org/10.1038/s41591-019-0439-x

13. Suez, J., Zmora, N., Segal, E. et al. The pros, cons, and many unknowns of probiotics. Nature Medicine 2019; 25, 716–729. Available from: https://doi.org/10.1038/s41591-019-0439-x

14. Zhang S, Chen D. Facing a new challenge: the adverse effects of antibiotics on gut microbiota and host immunity. Chinese Medical Journal. 2019;132(10):1135–1138. 15. Suez, J., Zmora, N., Segal, E. et al. The pros, cons, and many unknowns of probiotics. Nature Medicine 2019; 25, 716–729. Available from: https://doi.org/10.1038/s41591-019-0439-x

16. Ibid. 

17. Ibid. 

18. Freedman S, Pasichnyk D, Black K, Fitzpatrick E, Gouin S, Milne A et al. Gastroenteritis Therapies in Developed Countries: Systematic Review and Meta-Analysis. PLOS ONE. 2015;10(6). 

19. Yeh A, Morowitz M. Probiotics and fecal microbiota transplantation in surgical disorders. Seminars in Colon and Rectal Surgery. 2018;29(1):37-43.

20. Ibid. 

21. Ibid. 

22. Paramsothy S, Kamm MA, Kaakoush NO, et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. The Lancet. 2017. Available from: http://www.sciencedirect.com/science/article/pii/S0140673617301824.

23. Yeh A, Morowitz M. Probiotics and fecal microbiota transplantation in surgical disorders. Seminars in Colon and Rectal Surgery. 2018;29(1):37-43.

24. Daniells S. Probiota Champions: In conversation with Dr John Bienenstock [Internet]. nutraingredients-usa.com. 2020. Available from: https://www.nutraingredients-usa.com/Article/2020/12/04/Probiota-Champions-In-co nversation-with-Dr-John-Bienenstock

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