This study investigates the possible physiological effects of colonisation of the small intestine by bacteria from the large intestine following faecal transplantation (which mainly includes species from the large intestine). Different regions of the intestine have very different microbiota, and this cross-colonisation could cause alterations. The study primarily investigates this possibility using a model of mice treated with antibiotics that subsequently receive a faecal transplant made from microbiota from different parts of a donor's intestine. The study shows that the entire intestine is colonised from the transplant and not only (although more efficiently) the intestinal region equivalent to the origin. The researchers found that each intestinal region alters metabolites and functions in relation to the microbiota received, and even the gene expression patterns of intestinal tissue and liver cells can change.

The study has some limitations, particularly in the section on human data, where the number of patients analysed is very small (seven). The analyses in mouse models, on the other hand, are very comprehensive and use appropriate techniques.

Given that the microbiota differs depending on the origin of the transplant, it is to be expected that differences will be found at the metabolic and tissue response levels.

The questions that remain open are how long these changes last and whether they are harmful, as suggested by the conclusions. Any alteration of the microbiota, such as that resulting from antibiotic treatment, will have physiological repercussions, and it would be interesting to have some point of comparison beyond the variable origin of the transplant.

The study opens our eyes to how little we still know about the impact of faecal transplantation and proposes exploring combined transplants from multiple sources (omnimicrobial). Overall, more clinical and basic research is needed to understand the true therapeutic potential and possible side effects of faecal transplantation.

"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".

The study aims to assess the impact of faecal microbiota transplantation (FMT) on the microbial ecosystem of the gastrointestinal tract, with a particular focus on the changes induced in the small intestine and their possible consequences on host homeostasis.

For this purpose, the authors used murine models and, in the human case, organoids derived from duodenal biopsies. However, it is important to note that the human study had a very small sample size and a follow-up restricted to only one month. Both the experimental design, the small sample size and the short duration of follow-up in humans are relevant methodological limitations that should be taken into account when interpreting the results.

The results of the study indicate that TMF causes alterations in the composition and function of the gut microbiota, affecting host metabolism as well as intestinal and liver transcriptomic profiles. The authors conclude that TMF induces modifications in the intestinal bacterial ecosystem that could have adverse consequences for host health and metabolism.

Despite these findings, currently available scientific evidence considers TMF a safe procedure, especially in the short term, provided it is performed under controlled conditions and complies with quality, safety and legal standards. In addition, multiple clinical trials have demonstrated its high efficacy and safety in the treatment of recurrent Clostridioides difficile infection.

While this study suggests that TMF may induce disruptions in host homeostasis through alterations of the microbial ecosystem, its methodological limitations prevent drawing firm conclusions. Nevertheless, this work highlights the need for further research on the effects of TMF, particularly with regard to its impact on the small intestine and its applicability in other clinical settings.