Could We Use Gut Microbes To Treat Obesity, Cancer and More?

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Numerous studies show that the diversity of microbes that live in the human gut decreases with advancing age. Not only that, but the expansion of some strains of bacteria at the expense of others is correlated with the risk of certain diseases. As the saying goes: correlation does not necessarily mean causation. To show that the composition of the gut microbiome influences the risk of disease, we need randomised, placebo-controlled clinical trials in which we randomly assign participants microbiome-targeting therapies and see if this reduces disease risk. Unfortunately, not that many trials of this nature have been done. This study provides a summary of those that do exist and what we can learn from them, with a focus on clinical trials for faecal microbiota transplant (FMT). FMT involves taking stool from a healthy individual and delivering it to the recipient’s gut, such as via colonoscopy or orally. It’s the only way to fully and permanently restore the human gut microbiome to a healthy state, since probiotics are not native to the human gut and so don’t survive there for very long.

Key takeaways:

• Therapies targeting the gut microbiome such as faecal microbiota transplant (FMT) have underexplored potential for treating numerous diseases.
• FMT was recently approved as part of treatment for C.difficile infection due to its success in clinical trials
• Despite the relationship between the gut microbiome and obesity, there’s mot much evidence that targeting the microbiome promotes weight loss in humans.
• There is some early evidence that supplements containing Bifidobacterium can improve the response to immunotherapy in cancer patients, but better clinical trials are needed.
• There is conflicting but generally favourable evidence that FMT can help resolve flare-ups and extend remission in patients with ulcerative colitis.

C.difficile infection

C.difficile is a dangerous bacterial infection of the colon, usually acquired in hospital and with a 6% mortality rate and a high likelihood of recurrence. Randomised trials over the past decade have shown convincingly that faecal microbiota transplants significantly improve C.difficile survival, recovery and reduces risk of relapse. The first such trial published in 2013 found that 93.8% of patients recovered after two FMT treatments following an antibiotic treatment, compared to only 31.8% of patients receiving antibiotics and a ‘fake’ FMT treatment. Other studies have found various different routes for FMT delivery such as oral capsules and colonoscopy-delivered FMT to be similarly effective. This culminated in the US Food and Drug Administration (FDA) approving FMT as a treatment for C.difficile.

FMT is likely to help with C.difficile in two main ways. Firstly, the healthy donor microorganisms compete with C.difficile in the gut and help ‘retake’ the niche that C.difficile has exploited. Secondly, they help re-establish a healthy gut microbiome after its disruption by antibiotics, which are a major reason why C.difficile occurs in the first place and subsequently reoccurs after it is treated.

Obesity

We know that the gut microbiome is disrupted in obesity. There are also multiple animal studies showing that when gut bacteria from obese humans are transplanted into mice, these mice develop obesity and resistance to the blood sugar lowering hormone insulin. Despite this, the clinical trials identified by the authors in which obese humans were given faecal microbiota transplants or specific beneficial bacterial strains have mostly been disappointing. None of them were significantly associated with weight loss, though delivering one type of bacteria (Akkermansia muciniphila) was associated with improved insulin sensitivity.

Gut bacteria play a role in fat metabolism as well as regulating inflammation and insulin sensitivity. The lacklustre human evidence doesn’t necessarily mean that the gut microbiome doesn’t play a role in obesity, but it seems as though we may not yet understand its role well enough to produce effective microbiome-manipulating therapies.

Cancer

It might come as a surprise to hear that the gut microbiome could have anything to do with cancer. However, the gut microbiome has a significant impact on the immune system since the two are in constant contact within the gut, and it is the immune system that is responsible for attacking and destroying cancer cells. Studies suggest that cancer patients don’t respond as well to immunotherapy when they are receiving antibiotics, which has led some trials to explore the possibility that the microbiome could impact the effectiveness of immunotherapy. 

Only two clinical trials met the researchers’ inclusion criteria, but both found that responsiveness to immunotherapy was significantly improved in patients receiving supplements containing Bifidobacterium. However, both trials had small sample sizes and were open label (both the patients and the physicians knew who was receiving which treatment) so we are waiting for the results of ongoing clinical trials before drawing any firmer conclusions.

Ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon of unknown cause. Some scientists think that the gut microbiome may play a role, since studies show that antibiotic use, lack of overall microbiome diversity, as well as an abnormal abundance of certain strains of bacteria correlates with risk and severity of the disease. So far the human evidence that the microbiome can be targeted as part of UC treatment is promising but not entirely conclusive. 

A majority of the 18 studies that met the researchers’ criteria found that FMT (or specific selections of bacterial strains in some cases) significantly improved the effectiveness of other treatments when it came to resolving flare-ups and keeping patients in remission. However, some of the studies found no significant benefit to FMT as well as negative side effects, so larger studies may be required to paint a clearer picture of its effectiveness. It has been suggested that the effectiveness of FMT may strongly depend on the patient and their existing microbiome.

The Take-Home Message

Even though we’ve known about the importance of the gut microbiome for human health for decades now, there are still many unanswered questions and a lot of untapped potential when it comes to treating diseases. One of the reasons it is so hard to get a clear picture of the effectiveness of these treatments is that everyone’s gut microbiome is different, which means that the stool from FMT donors is also different. When you combine this with the fact that the recipient’s diet and immune system will interact with the new microbiome, it’s not hard to see how the effectiveness of FMT could be quite inconsistent.