The Science Behind Fecal Microbiota Transplantation: A Mechanistic Overview

The Role of the Gut Microbiome and the Consequences of Dysbiosis

The human gut is home to trillions of microorganisms that collectively form the gut microbiome. This complex microbial community plays a crucial role in various physiological processes, including digestion, immune regulation, and metabolism. Dysbiosis, or an imbalance in the gut microbiome, has been implicated in the pathogenesis of numerous diseases.

Mechanism of Action of FMT

FMT restore microbial diversity, suppress the growth of pathogenic microorganisms, and strengthen the intestinal barrier.

FMT works by introducing a diverse and healthy microbial community into a dysbiotic gut. This microbial infusion can restore microbial diversity, suppress the growth of pathogenic microorganisms, and strengthen the intestinal barrier. The gut microbiome comprises the community of microorganisms in the intestinal tract. Over the last five years, interest in the gut microbiome has grown considerably driven by new techniques in DNA sequencing allowing for characterisation of gut bacteria and the recognition of the potential impact the microbiome may have on health [1], [2]. The large intestine has the highest number of microbial organisms, with less found in the more hostile low-pH environment of the small intestine. The large intestine is dominated by anaerobic bacteria which survive and thrive by anaerobically digesting our food [3], [4], [5]. The gut microbiome has coevolved with humans to match our modern lifestyles [6] and is beneficial for our health, supplying essential nutrients, synthetizing vitamins (i.e. vitamin K) and facilitating digestion of undigested carbohydrates [7], [8], [9]. Furthermore, bacteria also help maintain the integrity of the mucosal barrier by preventing antigens and pathogens entering the gut mucosa [10], [11].

In healthy adults, 80% of the identified faecal microbiota can be classified into three dominant phyla: Bacteroides, Firmicutes and Actinobacteria. In general terms, the Firmicutes to Bacteroides ratio is regarded to be of significant relevance in the human gut microbiota composition. High Firmicutes and low Bacteroides usually correlates with a healthy diverse microbiome and reflects a largely plant-based diet. In unhealthy microbiomes the opposite is the case and may well be due to a more western type diet [12], [13]. Alterations in the composition of the microbiome has the potential to significantly impact on our health and wellbeing. One of the side effects of antibiotic use is a change in gut microflora that allows overgrowth of harmful micro-organisms [14]. Clostridium Difficile-associated diarrhoea for example is a well-recognised infection linked to previous antibiotic use [15]. Furthermore, studies on young children with a developing microbiome have shown that antibiotics are especially likely to cause long lasting adverse changes [16], [17], [18]. Regulation of the gut flora has also been correlated with a host of inflammatory and immune conditions [19], [20]. Recent changes in lifestyle including reduced exposure to pathogens in early life, dietary changes to a high intake of carbohydrates and fats from processed foods and reduced dietary fibre have been proposed to play a role in the rise of inflammatory conditions such as inflammatory bowel disease (IBS/D) and Crohn’s disease [19], [20]. The microbiome has been shown to have profound effects in the development of gut-associated lymphoid tissue, differentiation of gut immune cells and production of immune mediators such as IgA’s and microbial defence peptides [21]. Recent research suggests that an altered microbiome may play a role in a wide range of disorders including Parkinson’s disease [22], [23] chronic liver disease [24], [25], myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [26], [27] and also impact cancer patient recovery after treatments such as chemotherapy and radiotherapy [28]As a result, FMT can alleviate inflammation, improve digestive function, and modulate the host immune response.

Clinical Applications of FMT

FMT has shown promising results in the treatment of several conditions, including:

• Recurrent Clostridioides difficile infection (rCDI): FMT is considered the gold standard for the treatment of rCDI, which is often resistant to antibiotic therapy.

• Inflammatory bowel diseases (IBD): FMT has the potential to alleviate inflammation and improve clinical outcomes in patients with Crohn's disease and ulcerative colitis.

• Irritable bowel syndrome (IBS): FMT is being investigated as a potential therapy for IBS, which is characterized by abdominal pain, bloating, and altered bowel habits.

• Metabolic syndrome: FMT may improve metabolic parameters such as insulin resistance, obesity, and fatty liver disease.

• Neurological disorders: FMT has shown promise in the treatment of gastrointestinal symptoms associated with autism spectrum disorders and may also have therapeutic potential for other neurological conditions such as Parkinson's disease and multiple sclerosis.

• Other conditions: FMT is being explored for the treatment of various other conditions, including liver diseases, cardiovascular diseases, and certain types of cancer.

References

1. Role of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic organ. C.M. Guinane, P.D. Cotte. Therap Adv Gastroenterol, 6 (4) (2013), pp. 295-308

2. The gut microbiota and host health: a new clinical frontier. J.R. Marchesi, et al.. Gut, 65 (2) (2016), pp. 330-339

3. A human gut microbial gene catalogue established by metagenomic sequencing. J. Qin, et al.Nature, 464 (7285) (2010), pp. 59-65

4. Faecalibacterium prausnitzii and human intestinal health. S. Miquel, et al.. Curr Opin Microbiol, 16 (3) (2013), pp. 255-261

5. Structure, function and diversity of the healthy human microbiome. C. Human Microbiome Project. Nature, 486 (7402) (2012), pp. 207-214

6. Evolution of mammals and their gut microbes. R.E. Ley, et al.. Science, 320 (5883) (2008), pp. 1647-1651

7. Flavonoid metabolism: the interaction of metabolites and gut microbiota. K. Murota, Y. Nakamura, M. UeharBiosci Biotechnol Biochem (2018), pp. 1-11

8. Microbiota-derived tryptophan indoles increase after gastric bypass surgery and reduce intestinal permeability in vitro and in vivo. M. Jennis, et al. Neurogastroenterol Motil, 30 (2) (2018)

9. Host-gut microbiota metabolic interaction. J.K. Nicholson, et al. Science, 336 (6086) (2012), pp. 1262-1267

10. Study of the ability of bifidobacteria of human origin to prevent and treat rotavirus infection using colonic cell and mouse model. PLoS ONE, 11 (10) (2016), Article e0164512

11. A secreted bacterial peptidoglycan hydrolase enhances tolerance to enteric pathogens. K.J. Rangan, et al.. Science, 353 (6306) (2016), pp. 1434-1437

12. A core gut microbiome in obese and lean twins. P.J. Turnbaugh, et al. Nature, 457 (7228) (2009), pp. 480-484

13. Human intestinal microbiota composition is associated with local and systemic inflammation in obesity. F.J. Verdam, et al.. Obesity (Silver Spring), 21 (12) (2013), pp. E607-E615

14. Association between prior antibiotic therapy and subsequent risk of community-acquired infections: a systematic review. U. Malik, et al.. J Antimicrob Chemother, 73 (2) (2018), pp. 287-296

15. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. K.A. Brown, et . Antimicrob Agents Chemother, 57 (5) (2013), pp. 2326-2332

16. Resilience of the dominant human fecal microbiota upon short-course antibiotic challenge. M.F. De La Cochetiere, et al.. J Clin Microbiol, 43 (11) (2005), pp. 5588-5592

17. Effect of antimicrobial agents on the ecological balance of human microflora. A. Sullivan, C. Edlund, C.E. Nord. Lancet Infect Dis, 1 (2) (2001), pp. 101-114

18. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. H.E. Jakobsson, et al. PLoS ONE, 5 (3) (2010), Article e9836

19. Gut bacteria in health and disease. E.M. Quigley. Gastroenterol Hepatol (N Y), 9 (9) (2013), pp. 560-569

20. Bugging inflammation: role of the gut microbiota. S. Shen, C.H. Wong. Clin Transl Immunol, 5 (4) (2016), Article e72

21. The gut microbiota–masters of host development and physiology. F. Sommer, F. Backhed. Nat Rev Microbiol, 11 (4) (2013), pp. 227-238

22. Progression of Parkinson's disease is associated with gut dysbiosis: two-year follow-up study. T. Minato, et al.PLoS ONE, 12 (11) (2017), Article e0187307

23. Gastrointestinal dysfunction in Parkinson’s disease. A. Fasano, et al. Lancet Neurol, 14 (6) (2015), pp. 625-639

24. Nonalcoholic fatty liver disease is associated with dysbiosis independent of body mass index and insulin resistance. H.E. Da Silva, et al. Sci Rep, 8 (1) (2018), p. 1466

25. Review article: the gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease. C.A. Woodhouse, et al. Aliment Pharmacol Ther, 47 (2) (2018), pp. 192-202

26. Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome. L. Giloteaux, et al. Microbiome, 4 (1) (2016), p. 30

27.Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome. D.Nagy-Szakal, et al., Microbiome, 5 (1) (2017), p. 44

28. Microbiota: a key orchestrator of cancer therapy, S. Roy, G. Trinchieri. Nat Rev Cancer, 17 (5) (2017), pp. 271-285

The Science Behind Fecal Microbiota Transplantation: A Mechanistic Overview

In today’s world, we're increasingly aware of the intricate connection between our gut health and overall well-being. From digestive issues to chronic diseases, the gut microbiome plays a pivotal role. While conventional treatments often provide temporary relief, Fecal Microbiota Transplantation (FMT) offers a groundbreaking approach to restoring gut health and potentially treating a wide range of conditions.

Understanding Fecal Microbiota Transplantation

FMT is a medical procedure that involves transplanting healthy stool from a screened donor into the colon of a recipient. This process aims to restore a healthy balance of gut bacteria, which can be disrupted by various factors such as antibiotic use, infections, and underlying medical conditions.

Fecal Microbiota Transplantation (FMT): Reshaping the Gut Microbiome

Fecal Microbiota Transplantation (FMT) is an innovative therapeutic approach that has gained significant attention in the treatment of gastrointestinal disorders. This procedure involves transferring fecal matter from a healthy donor to a recipient with a disrupted gut microbiome. By restoring a healthy microbial balance, FMT aims to alleviate a wide range of conditions that are often resistant to conventional therapies.