There is an ecosystem of millions of microbes such as bacteria, viruses, fungi or archaea that populate the human gut and play key roles in health. All of them, their genetic material, the substances they secrete, and the relationships they form with one another make up the gut microbiome, a sort of invisible organ that interacts with the rest of the organism. When everything is in order and harmony, there is health; But when something becomes deregulated in this microbial universe — for example, due to the use of antibiotics or the emergence of a pathogen — problems arise.
The potential of the microbiome to mediate health and disease is still under investigation, but therapeutic strategies have already been found demonstrating its relevance to human well-being: fecal microbiota transplantation, which uses feces to transfer them to the gut Implanting gut microbes from a healthy donor in patients to restore their damaged flora is already being used in clinical practice. According to a scientific study, it is more effective than antibiotics in treating recurrent infections caused by Clostridioides difficile bacteria and may have a head start in ulcerative colitis. However, the scientific community continues to refine this technique and look for new indications, for example in the field of mental health or to improve the effects of immunotherapy in cancer.
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The idea of using feces – and its microbes – for therapeutic purposes is nothing new. As early as the fourth century, the use of so-called “Yellow Soup,” a stool suspension used to treat severe food poisoning and diarrhea, was described in China. The Bedouins also consumed camel dung to treat dysentery, and for this purpose intestinal bacteria were administered to German soldiers during the North African campaign in World War II.
“It was in the 1980s when it was used to treat Clostridioides difficile (C.difficile) infections,” explains Jordi Guardiola, head of the Digestive Organs Unit at Bellvitge Hospital in Barcelona and one of the heads of the department for studies that Microbiome of his center: “It is an infection closely linked to the use of antibiotics. Creates a profound dysbiosis [una alteración del equilibrio microbiano]. C.difficile is capable of forming spores that live anywhere and survive for long periods. We certainly had contact with them, but nothing happens to healthy adults. However, taking an antibiotic encourages dysbiosis and the spores germinate, and with this imbalance there is an increased risk of the toxin triggering inflammation,” he reports. Dysbiosis leads to loss of microbial diversity: beneficial microorganisms disappear in favor of the proliferation of other potentially harmful microorganisms.
Guardiola emphasizes the paradox of using antibiotics to treat an infection that is being fueled by the very use of the same drugs: “A disease favored by antibiotics, we treat it with more antibiotics: we kill the bacteria, but we cause more dysbiosis and that means “which increases the risk of recurrence,” he warns. This highly resistant microorganism can cause life-threatening diarrhea and after the first infection, 30% of patients treated with antibiotics will relapse; After the second episode, there is a 60% chance of a third episode.
In clinical practice, transplantation of faecal microbiota is already used to treat this disease. Through a colonoscopy, including using an enema, oral capsules, or a nasogastric tube, the patient is given fecal material containing gut microbiota from a healthy donor: the technique helps restore flora and increase microbial diversity. A study published in the New England Journal of Medicine (NEJM) in 2013 confirmed the resounding success: 93% of the patients were cured with the transplant and only 31% with an antibiotic. “The study was discontinued. [antes de tiempo] because the benefits were very high,” Guardiola recalls.
A culture of “Clostridioides difficile” in the laboratory of the microbiological service of the Hospital de Bellvitge. Albert Garcia
A recent review by Cochrane, the independent network of researchers that analyzes evidence, concludes that stool transplantation “is likely to result in significantly better cures for recurrent C. difficile infections compared to alternative antibiotic treatments” such as vancomycin. Rosa del Campo, a microbiologist at the Ramón y Cajal Hospital in Madrid, welcomes the result of the study, although it is nothing new to her. “From the third repetition it occurs. And people take it very well. However, our doctors prefer to consider other options such as fidaxomicin [otro antibiótico]because they believe that we are taking certain risks,” admits the microbiologist.
The question of the risks of this therapy strategy is still open. In this case, the scientific review concludes that this technique “is likely to result in a small reduction in serious side effects,” but the authors acknowledge “concern” about the possibility that pathogens could be introduced into the transplant that cause side effects undesirable: “Serious events such as mortality, septic shock, aspiration pneumonia and toxic megacolon have been reported,” they reflect. Del Campo assumes the dangers, but there are also controls, he restricts: “There are risks.” [introducir] Things we don’t know but the donors are healthy and super controlled people. “In Spain, we always carry out checks to detect antibiotic-resistant bacteria in the faeces,” he explains.
Not everyone is worth a donor. The profiles are carefully monitored — “If you have high cholesterol, we rule that out,” Del Campo says — and they’re tracked for a period of time to make sure they’re still healthy people. There is not a zero risk, but the risk of transmission of infections does not worry the experts too much, emphasizes Guardiola: “On the contrary: the normalization of a microbiota makes you healthier and prevents intestinal sepsis.” What worries us now is, that the predisposition to get sick is transmitted. This is more theoretical, but strictly speaking, if a donor develops an illness, the recipient needs to be monitored. We transfer many things that we don’t know what they are.”
Microbiome research continues. Another Cochrane review of its role in inflammatory bowel disease (IBD) — an autoimmune disease that affects the gut where the immune system mistakenly attacks healthy tissue — comes up with more mixed results: The researchers conclude that it’s “the proportion of people with peptic ulcer disease.” Colitis [un tipo de EII] those who manage to get the disease under control” but see “uncertain” evidence of the risk of side effects or an improvement in quality of life. It is also not clear whether it is used to help patients with Crohn’s disease (another type of IBD) into remission or to maintain an eventual remission of either of these two conditions.
No results for Crohn’s disease
“There is a clear link between dysbiosis and IBD, and this has led to the assumption that if you normalize this imbalance, you can reduce the disease.” Most of the randomized trials of ulcerative colitis were positive, but not all,” recalls Guardiola . Del Campo points out that for colitis to work, “you don’t have to be a long-term patient”: “In these cases, the immune system is already so altered that even if you change the bacteria, the inflammation doesn’t go away.” , he explains. In the case of Crohn, the experts surveyed agree that the situation is more heterogeneous, “there is less data” and it doesn’t quite work.
Outside of intestinal pathology, stool transplantation is also studied. Del Campo, for example, points to recurring urinary tract infections: “It is currently being investigated. It’s about changing the ecosystems of the gut if uropathogens are hidden there. The alternative is to take low-dose antibiotics every day of the year.” Guardiola also points out possibilities “for preventing sepsis in multi-resistant germs” or for oncology: “There is a clear connection between dysbiosis and the effectiveness of immunotherapy and there are studies conducted to improve cancer treatment,” he says. A small study published in Science showed that in patients with metastatic melanoma, stool transplantation was associated with “beneficial changes” in immune cells and gene expression in the tumor environment.
There are also some green shoots in mental health that emphasize the gut-brain axis, that bidirectional pathway connecting the two organs. For example, in a patient with bipolar disorder, Australian doctors achieved post-transplant symptom relief and ruled out a possible placebo effect: “I felt incredible, as if a load had been lifted from my shoulders.” Would have been able to breathe again in years,” said the patient himself after the procedure, whose statements were collected in the study. A scientific review including human and preclinical studies also found “strong evidence” for the treatment and transmission of psychiatric disorders through faecal transplantation. “All studies found a reduction in depressive and anxiety-like symptoms and behaviors as a result of healthy microbiota transplantation. The opposite has also been found, namely the transmission of depressive and anxiety-like symptoms and behaviors as a result of microbiota transplantation from psychiatrically ill donors to healthy recipients.
The scientific community continues to explore, including using well-characterized laboratory-developed bacterial cocktails to control what is administered in the transplant. The US Food and Drug Administration (FDA) approved the first pre-packaged fecal microbiota biomedicine against Clostridioides difficile in November. “The real limitation we have is the knowledge, the knowledge base that we lack,” Del Campo assumes. Guardiola agrees: “We still have a lot to learn. We have always been very cautious about the association between dysbiosis and disease: except in Clostridioides, a causal relationship has not been established. And finding connections does not mean that there is causality.”
Many questions still have to be clarified. An article published in the journal Cell Host & Microbe highlights that even the mechanical understanding of how stool transplantation works in C.difficile is “incomplete” and that they don’t know why this technique doesn’t work in some patients. For example, they claim that environmental factors such as the recipient’s diet or genetics have not been considered in previous studies, “and may be the missing links in these cases of transplant failure,” they posit.
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