Microbiome-based therapeutic milestone
In May, 2023 a significant milestone was achieved in the field of applied microbiome research. The U.S. Food and Drug Administration (FDA) approved Vowst, the first fecal microbiota product that is taken orally. Vowst is approved for the prevention of recurrence of Clostridioides difficile (C. difficile) infection (CDI) in individuals 18 years of age and older. In this post, we will briefly discuss the details and the significance of this approval.
Human microbiome and Clostridioides difficile infection
The human intestinal tract contains millions of microorganisms, often referred to as the “gut flora" or "gut microbiome". It is well established that the gastrointestinal (GI) microbiome plays a crucial role in overall homeostasis, and changes in its components may either progress or slow down the disease development. The team at Pretty Light Science has tackled this topic before, when we talked about how the gut microbiome affects our mental health and our motivation to exercise. The GI microbiome is an incredibly complex community of microorganisms containing hundreds of species that all interact between each other and with the host. From fermented foods and beverages to microbiome-based therapeutics, the human microbiota has been manipulated by people for a long time in an attempt to fight diseases and strengthen the immune system [1]. C. difficile infection (CDI) has been recognized as one of the leading causes of healthcare-associated infections and a considerable threat to public health globally [2].
Some patients recovered from CDI may get the infection again—often multiple times—a condition known as recurrent CDI (rCDI). This condition is linked to dysbiosis, or imbalance, of the GI microbiome. Common treatments against rCDI, such as taking antibiotics, may alter the microbial community in the gut by targeting both beneficial and harmful bacteria. This gives C. difficile the opportunity to multiply, spread, and release toxins causing a range of negative effects including diarrhea, abdominal pain and fever, and in some cases leading to organ failure and death.
What is Vowst and what are its acting agents?
Vowst is the first FDA approved fecal microbiota-derived product that is taken orally. It is manufactured by Seres Therapeutics Inc. from human fecal matter and it contains live bacteria whose aim is to outfight C. difficile and repopulate the gut with a healthier bacterial community. The dosing regimen of Vowst is four capsules taken once a day, orally, for three consecutive days.
How effective is Vowst?
A randomized, placebo-controlled study was used to assess the effectiveness of Vowst to reduce the probability of CDI recurrence in 182 participants who had had three or more episodes of recurrent C. difficile infection. During 8 weeks after treatment, the number of CDI recurrence cases was lower in the Vowst-treated group of participants compared to the control group (12.4% compared to 39.8%, respectively).
The number of CDI recurrence cases was lower in the Vowst-treated group (12.4%) compared to the control group (39.8%).
Does Vowst have any side effects?
There is a possibility that Vowst may contain some transmitting infectious agents. It is also possible for Vowst to contain food allergens whose ability to cause adverse reactions hasn’t been studied yet. In addition, the most commonly reported side effects by Vowst recipients compared to the control group, include abdominal bloating, fatigue, constipation, chills, and diarrhea.
What’s next for microbiome-based therapeutics?
The first microbiome-based C. difficile therapy, Rebyota, was approved by FDA in late 2022. This drug, prepared from stool samples donated by qualified individuals, is administered rectally as a single dose. Other microbiome-based drugs are currently in development. This includes bacterial consortia designed by Vedanta Biosciences which are created by growing bacterial strains directly from pure clonal cell banks. According to Vedanta Biosciences, this is a “highly scalable process that obviates the need for fecal donors and leads to a consistently manufactured candidate”. In addition to CDI, scientists and clinicians are working on developing microbiome based therapeutics for other diseases caused by imbalance in the GI microbiome, including irritable bowel syndrome (IBS) and Crohn’s disease.
Reference:
Finn E, Andersson FL, Madin-Warburton M. Burden of Clostridioides Difficile infection (CDI) - a systematic review of the epidemiology of primary and recurrent CDI. BMC Infect Dis. 2021;21(1):456.
Gulliver EL, Young RB, Chonwerawong M, et al. Review article: The future of microbiome-based therapeutics. Aliment Pharmacol Ther. 2022;56(2):192-208.
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