Reacción a "A study in mice suggests that faecal microbiota transplantation could have unexpected effects on other areas of the digestive system"

"This study has been published in one of the world's most reputable scientific journals and presents scientific evidence that the colonisation of bacteria in disparate ecosystems, such as bacteria that normally inhabit the large intestine colonising the small intestine, has a potentially deleterious effect in an experimental model of faecal microbiota transplantation in mice and in cells obtained and cultured ex vivo from human intestinal biopsies (organoids). The conclusion that these models warn us of unexpected dangers in patients receiving FMT —faecal microbiota transplantation— does not necessarily follow from the results of the article, despite its high scientific value.

In medicine, the validity of treatments is constantly evaluated based on their efficacy and safety in patients undergoing a specific intervention. Since the implementation of new European regulations classifying microbiota as a substance of human origin (SOHO), the mechanisms for verifying the biological safety of donations and monitoring patients who have undergone microbiota transplantation are now well regulated. The scientific method in medicine for questioning the validity of an intervention should be the adverse effects observed after the intervention, not experimental observation in mice. Let us recall the controversy surrounding saccharin and bladder cancer in mice in the 1970s.

FMT has been performed safely for years and is a curative treatment for recurrent infection with Clostridioides difficile. Far from inducing a negative metabolic change in patients, in controlled clinical trials, FMT in obese adolescents was found to reduce metabolic syndrome in 90% of cases".

How do the results of this article translate to patients receiving FMT?

"Fecal transplantation in mice has nothing to do with humans —fortunately— since the microbiota is administered by feeding the mouse the feces (microbiota) of a healthy mouse. In humans, although initial studies (in fact, the most important ones) used duodenal infusion of microbiota, it is currently administered by colonoscopy in the cecum or by capsules coated with a gastro-resistant material that allows the contents of the microbiota to be released into the large intestine, although some may be released in the terminal part of the small intestine.

The impact of ecological disruption and relocation of bacterial species is a well-known and partially characterised phenomenon in human microbiome studies. For example, it is well known that in individuals taking proton pump inhibitor drugs, the oral microbiota colonises the intestine. The various segments of the intestine act as ecosystems where the physicochemical conditions of pH, the intestinal cells themselves and, above all, the resident microbiota act as a brake on the colonisation of new species, which has been known since 1960 as colonisation resistance. Therefore, although the risk of microbial colonisation in disparate ecosystems is a possibility, the local mechanisms described above ‘select’ who stays and who goes. This is the usual competition through which the adult microbiota is established and which also explains one of the most notable characteristics of the microbiota: resilience or the ability to return to its usual state after an ecological disruption, whether due to antibiotics or other disruptors. Paradoxically, this is the argument put forward to defend the potential use of omnimicrobial transplants, where microbiota are collected from different sections of the intestine and it is proposed that each will settle in its appropriate ecological niche. The same is true of the colon microbiota: its natural place of settlement will be the colon, and it is there that it will restore resistance to colonisation by Clostridioides difficile, which is, for the time being, its only approved clinical indication".