C. diff is a bacteria that notably has a hospitalization rate of about 50 percent and carries a list of symptoms including diarrhea, fever, and stomach tenderness or pain. (Kateryna Kon/Shutterstock)

C. difficile (C. diff) is a bacterial infection that affects nearly half a million Americans each year. Paradoxically, treatment for the disease often uses strong antibiotics—yet antibiotic use is a major risk factor for contracting the disease. Despite issuing warnings three years ago, the U.S. Food and Drug Administration (FDA) recently approved the first-ever standardized fecal therapy to treat C. diff infections. 

C. Diff Infections Occur When Good Bacteria Dies

A balance persists in the gut microbiome that allows us to live a healthy life. It is a system that ensures we have the right amount of each bacteria needed in our intestinal tracts. More research is emerging showing that an imbalance in the gut microbiome can lead to a number of issues—one of them being a C. diff infection.

C. diff is a bacteria that notably has a hospitalization rate of about 50 percent and carries a list of symptoms including diarrhea, fever, and stomach tenderness or pain. Although C. diff can affect anyone, it is more likely for someone to be infected after taking antibiotics.

Antibiotics neutralize a large number of good and bad bacteria which results in the gut flora being out of balance, creating an environment in which C. diff can thrive. Other risk factors for C. diff include being 65 and older, having a weakened immune system, and visiting a high-risk environment such as a hospital or nursing home. It is important to note that anyone can be affected by C. diff.

Treating C. diff is a bit paradoxical in practice. Typically, doctors prescribe antibiotics against bacterial infections—yet taking antibiotics is the largest risk factor for contracting C. diff. Still, some doctors prescribe a stronger antibiotic for about 10 days should the symptoms be severe.

Another therapeutic treatment for C. diff infection is an IV infusion prophylaxis marketed under the name Zinplava, a concentrate with its active ingredient being the human monoclonal antibody bezlotoxumab. In two clinical studies, Zinplava reduced recurring episodes of diarrhea to about 16 and 17 percent compared with 26 and 28 percent from the control group, meaning it was slightly more effective than the placebo.

Recently, the FDA approved a novel treatment method: Stool based colon injections to treat C. diff.

Fecal Microbiota Product to Treat C. Diff

On Nov. 30, 2022, the FDA officially approved the first “Fecal Microbiota Product” called Rebyota. These products, also known as stool transplants, generally fall under the category of fecal microbiota therapy, or FMT.

“Today’s approval of Rebyota is an advance in caring for patients who have recurrent C. difficile infection,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. He noted that recurrent C. diff infections “can also potentially be life-threatening” and says the approval marks “an important milestone” in treating the disease.

Rebyota has been granted fast track, breakthrough therapy, and orphan drug designations in 2013, 2014, and 2015 respectively. The FDA fully approved the treatment method just before December 2022.

Rebyota was developed by Rebiotix, which was later acquired by Ferring Pharmaceuticals, Inc. In development over the past decade, Rebyota is a microbiota-based, live biotherapeutic that works to facilitate restoration of the gut microbiome to prevent further episodes of infections. It is manufactured from human feces donated by individuals and screened for transmissible pathogens such as Hepatitis, HIV, and other diseases per doctor recommendations.

Stool donations are purified and processed for administration to the patient. Reintroducing processed stool from healthy individuals has shown some success in clinical trials. The overall success rate in preventing a recurrent C. diff infection was about 70.6 percent in the FMT group compared with 57.6 percent in the placebo group, somewhat similar when compared to results using Zinplava.

However promising the data may look, there are some side effects to consider with this novel treatment. 

Treatment is usually delivered via colonoscopy, or less commonly, through a tube inserted via the nose to the duodenum—a method associated with a higher risk of side effects such as aspiration pneumonia. Other side effects may include stomach pain, diarrhea, bloating, gas, and nausea. Patients are instructed to not take any oral antibiotics for 8 weeks after Rebyota treatment.

The manufacturers have noted that because Rebyota is manufactured from human fecal matter, patients should prepare themselves for adverse allergic reactions after treatment as allergens may well be in the donor’s sample.

Warnings From the Past

History has not always been in FMT’s favor. The FDA issued a statement warning against the possible risk of allergen transmission when administering FMT in 2019 citing the possibility of allergen transmission and a potentially hazardous spread of what are known as superbugs that include bacteria, fungi, etc., resistant to antibiotics and other common forms of medication. 

Superbugs have been a growing concern for the medical community as they have the potential to render prescribed medication less or ineffective. In 2019, a study showed that superbugs have directly caused the death of over a million people around the world, with almost 5 million deaths related to them.

FMT treatment is usually screened for possible pathogens before entering the stool bank to ensure that unwanted agents are not transmitted. However, the process has been updated over the past few years since incomplete screenings have resulted in hospitalizations or even death.

Most pathogens, once they infect the host, are present in most parts of the body including the stool. A pathogen simply needs a medium such that it can be transmitted from one host to another, this includes stool.

In 2020, the FDA issued a statement detailing the report of six patients who were infected with a form of E. Coli after receiving FMT. Four of six patients required hospitalization and attributed the infections to an incomplete screening process. Similar cases have appeared in the past which resulted in companies that perform FMT releasing statements in order to acknowledge the phenomenon and announce changes to their screening process.

A study shows that stool donations are usually accepted from volunteers up to two or three months after they were screened for pathogens and receive minimal processing. There is concern about the possibility that a donor may become infected with the disease between the screening time and the actual donation time.

Concerns still persist regarding this form of treatment.

A Simple Way to Keep Your Gut Healthy

FMT treatment, nevertheless, has seen increasing availability and has found gradual acceptance in the medical community over the past decade, yet it was mostly performed on a direct patient-to-donor basis. Rebyota simply industrialized the process and made it more commercially available, marking a milestone in the medical industry.

In recent years, it seems that the FMT industry has consolidated itself in the area of treating C. diff with other drugs in the pipeline—preparing itself for phase 3 trials. However, some manufacturers have the ambition to tackle inflammatory bowel disease, or IBD, a disease that affects more than 3 million Americans each year. IBD is an inflammatory disease that is strongly linked to a disruption in the balance of gut microbes, thus researchers are pitching FMT as a possible IBD cure to their investors.

Why FMT has an effect on C. diff is that it can replenish the gut microbiome in the intestines and restore the balance needed for good health. The bacteria spores from C. diff are especially likely to be activated in people who have undergone antibiotic treatment because it wipes out most of the pre-existing organisms, turning the intestines into a sandbox for C. diff to unleash havoc.

This is why in the case of gut-related diseases like C. diff and IBD, it is important to focus on the balance of gut microbes before infection occurs. 

The gut is an organ closely connected to the brain via the longest cranial nerve, the vagus nerve. The vagus nerve creates an interactive information exchange between the two organs and is responsible for mood and digestion amongst other body functions. As a healthy gut can put you into a good mood, a calm mindset can shift your gut into the right composition.

Studies conducted at the University of California and New York University have shown that meditation can smooth out gut irregularities and has a positive impact on the gut microbiome.

A comparison study between meditating and non-meditating groups of people showed that meditation results in stronger and more diverse gut microbes. Rather than wiping the intestine clean with antibiotics, it seems better to replenish and restore the balance in the gut.

Other papers focusing on meditation and gut-related diseases have shown that the positive aspects don’t stop there. New York-based researchers demonstrated in their experiment that the meditating group, when compared with the control, “was associated with significant … [reductions in] C-reactive protein [levels].” C-reactive proteins are an indicator of inflammation, a common cofactor in gut diseases, and a staple symptom of C. diff.

Additionally, a study conducted at a stress and anxiety center shows that meditation can relieve stress, abdominal pain, diarrhea, and other gastrointestinal symptoms with their patients seeing significant improvement after a period of time. Meditation works quite similarly to FMT in the sense that it replenishes your gut bacteria, with other studies showing that meditation can boost your immune system. Both are key to overcoming gut-related diseases such as C. diff.

Meditation is also quite safe. A study published in Psychological Medicine concluded that there is “no evidence that [meditation] leads to higher rates of harm” when the participants were compared with the control group. The study states meditation was, on many accounts, “significantly preventative of harm.”

Adjusting the diet may also improve gut-related issues. It is important to eat foods that contain a large number of live cultures or probiotics, such as kombucha, kefir, fermented goods such as sauerkraut, and foods rich in fiber like whole grains, fruits, and vegetables, among other things.

It is vital to avoid foods that are highly acidic, overly fatty or greasy, and raw. One also needs to stay hydrated, as that is a key in battling gut infections that commonly cause diarrhea as a cofactor. The Mediterranean diet, among many others, suits this best. It might be no coincidence at all that Italy has a low C. diff infection rate when compared with the U.S.

FMT is now an approved treatment method having gone through extensive regulatory controls with risks related to the treatment still being present. There are many methods to relieve the symptoms of an ill gut, such as the aforementioned eating and mindfulness habits one can develop. They are one of many options well worth considering to supplement the limitations of customary remedies.