FMT in Obesity

Given that gut dysbiosis has been implicated in obesity, and FMT improves gut flora, further research is warranted to clarify this connection and assess treatment potential. A case report published in 2015 identified an individual experiencing a disproportionate weight gain after undergoing FMT.17 A 32-year-old woman with recurrent C difficile infection underwent FMT from an obese donor. This patient experienced a rapid weight gain of >30 lb despite a supervised high-protein liquid diet and exercise program. In addition, a review by Marotz and Zarrinpar describes the exciting potential of FMT as a treatment for metabolic syndrome but cites the lack of randomized controlled trials that currently exist, which supports the need for and usefulness of further investigation into this topic.18 In a randomized, double-blind, controlled trial using gut microbiota transfer via gastroduodenal tube from a lean donor vs the subjects’ own gut microbial infusion, a statistically significant improvement in peripheral insulin sensitivity was seen 6 weeks following treatment.19

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As of this writing, researchers at Helsinki University Hospital in Finland have initiated a randomized control trial to assess FMT as a treatment for morbid obesity. A total of 40 patients meeting the criteria for obesity surgery have been enrolled and will undergo FMT via gastroscopy 6 months prior to obesity surgery; 20 of the patients will receive a fecal transplant from a thin donor and 20 will receive a transplant of their own feces. Changes in weight, laboratory values, general well-being, and stool microbiota will be measured up to one year after the surgery. Outcomes from this study are anticipated in early 2021.


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Michelle Petropoulos, DMSc, PA-C, DFAAPA, works in a private practice family medicine office in Madison Heights, Michigan.

Table. Generalization of Lean and Obese Intestinal Microbiome*

  Obese Lean
Microbial Diversity  
Firmicutes   ↓  
Bacteriodetes   ↑  
Proteobacteria   ↑↓   ↑↓  
Actinobacteria   Equivocal or ↑   Equivocal or ↓  
Firmicutes/Bacteriodetes ratio

*Conflicting data exist regarding the optimal microbiota for weight loss. Possible explanations include (a) Firmicutes are more effective as an energy source than Bacteroidetes, resulting in increased calorie absorption; (b) the association between the relative proportion of gut anaerobic and blood glucose levels;  (c) the abundance of various species within each phylum; (d) different study methodologies; and (e) the dietary habits of participants in specific geographic locations.3,11,12,14,20

References

1. World Health Organization. Obesity. World Health Organization website. https://www.who.int/topics/obesity/en/. Accessed August 20, 2019.

2. Centers for Disease Control and Prevention. Adult obesity causes and consequences. Centers for Disease Control and Prevention website. https://www.cdc.gov/obesity/adult/causes.html. Updated August 29, 2017. Accessed August 20, 2019.

3. Ursell LK, Haiser HJ, Van Treuren W, et al. The intestinal metabolome: an intersection between microbiota and host. Gastroenterology. 2014;146(6):1470-1476.

4. McNab BK. On the utility of uniformity in the definition of basal rate of metabolism. Physiol Biochem Zool. 1997;70(6):718-720.

5. Taousani E, Savvaki D, Tsirou E. Regulation of basal metabolic rate in uncomplicated pregnancy and in gestational diabetes mellitus. Hormones (Athens). 2017;16(3):235-250.

6. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007;449(7164):804-810.

7. Bäckhed F, Ding H, Wang T, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004;101(44):15718-15723.

8. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027-1031.

9. Million M, Lagier JC, Yahav D, Paul M. Gut bacterial microbiota and obesity. Clin Microbiol Infect. 2013;19(4):305-313.

10. Million M, Maraninchi M, Henry M, et al. Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii. Int J Obes (Lond). 2012;36(6):817-825.

11. Jayasinghe TN, Chiavaroli V, Holland DJ, Cutfield WS, O’Sullivan JM. The new era of treatment for obesity and metabolic disorders: evidence and expectations for gut microbiome transplantation. Front Cell Infect Microbiol. 2016;6:15.

12. Tremaroli V, Bäckhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489(7415):242-249.

13. Martinez KB, Pierre JF, Chang EB. The gut microbiota: the gateway to improved metabolism. Gastroenterol Clin North Am. 2016;45(4):601-614.

14. Allen JM, Mailing LJ, Niemiro GM, et al. Exercise alters gut microbiota composition and function in lean and obese humans. Med Sci Sports Exerc. 2018;50(4):747-757.

15. Graessler J, Qin Y, Zhong H, et al. Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters. Pharmacogenomics J. 2013;13(6):514-522.

16. de Clercq NC, Frissen MN, Groen AK, Nieuwdorp M. Gut microbiota and the gut-brain axis: new insights in the pathophysiology of metabolic syndrome. Psychosom Med. 2017;79(8):874-879.

17. Alang N, Kelly CR. Weight gain after fecal microbiota transplantation. Open Forum Infect Dis. 2015;2(1):ofv004.

18. Marotz CA, Zarrinpar A. Treating obesity and metabolic syndrome with fecal microbiota transplantation. Yale J Biol Med. 2016;89(3):383-388.

19. Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143(4):913-916.e7.

20. Jumpertz R, Le DS, Turnbaugh PJ, et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr. 2011;94(1):58-65.