The microbiome, particularly the individual microbiotas, have captured a lot of interest in a diversity of fields, which may open the potential for phage therapy against Ruminococcus gnavus. Particularly, the gut microbiota of patients with chronic inflammatory conditions such as; Hidradenitis suppurativa (HS), Inflammatory Bowel Disease (IBD); Crohn’s disease, and Ulcerative Colitis (UC). revealed a common abundance of Ruminococcus gnavus. The unique biology of natural lytic bacteriophages may hold potential therapeutic approaches towards addressing the abundance of the bacterial strain which is known to produce an inflammatory polysaccharide that may stimulate immune cells that trigger inflammation in patients.
The gut microbiota and phage therapy
The study of the influences of the gut microbiota on the overall state of the body is growing over the years. The relationship between the gut microbiota and various conditions has shown that the balance within the microbial community in the gut plays a role in the progression and/or suppression of certain conditions. The key to a healthy system through the approach of the gut microbiota is to create a balanced community within the gut.
Conventional medicine focuses on targeting pathogenic bacteria. This bacterium is viewed as a microbe that does not belong in the community and therefore, creates a disbalance. The understanding of pathogenic microbes from the aspect of microbiology shines a light on an even deeper understanding of the term pathogenic. The relationship between microorganisms in a community is delicate as the community has a limited space that must be shared amongst all members. If a certain member of the community increases its population or creates an abundance or overgrowth (causes include; certain medication and antibiotic intake, changes in pH levels, nutrition, stress, and other factors), it will inevitably take more space within the community. This particular member will be seen as a pathogen, not in terms that it is foreign to the community, but rather, that for some reason it has increased its population, causing a decrease in the population of other members and resulting in a disbalance within the entire community.
Bacteriophages are primarily known by many to be bacteria’s natural predators. However, a unique characteristic of natural lytic bacteriophages that is less spoken of, is their ability in assessing the population of their target bacteria within a community and acting upon that assessment. Research has shown that carefully selected lytic phages that target an entire group of bacteria, not strain-specific, do not simply destroy all strains. Rather, the bacteriophages minimize the population of the strain that caused an overgrowth, whilst allowing other strains to increase their population, which were previously lowered by the overgrowth. This careful approach of monitoring their target population, allows all strains to reach a balanced level, resulting in a balance within their community.
Ruminococcus gnavus belong to the family Ruminococcaceae and class of Clostridia. It is a member of the human gut microbiota and in a healthy state, represents <0.1% of the gut microbiota. One study highlighted that Ruminococcus gnavus produces an inflammatory polysaccharide that induces the production of cytokines such as TNF-alpha by dendritic cells, which are associated with flares in conditions such as; Hidradenitis suppurativa, Inflammatory Bowel Disease; Crohn’s disease, and Ulcerative Colitis.
Another study revealed that the polysaccharide produced by Ruminococcus gnavus can be a capsular polysaccharide and a polysaccharide lacking the functional capsule. It was observed that the capsular polysaccharide promoted a tolerogenic immune response, resulting in pro-inflammatory responses.
Hidradenitis suppurativa (HS) is a chronic inflammatory condition that presents itself on the skin and is characterized by the formation of nodules, abscesses and fistula at intertriginous sites. It is estimated that 4 in 100 people (as of 2020) suffer from HS. The estimate is due to the fact that the condition is many times misdiagnosed and many patients do not seek help due mainly to social stigma. Although not life-threatening, the condition has a profound impairment on Quality of Life (QoL) for patients.
Research surrounding the skin-gut axis has been emerging to understand the potential contributory factor of the pathogenesis of Hidradenitis suppurativa. In a study consisting of 59 HS patients samples were collected to study the state of the patients’ faecal, nasal and skin microbiotas. Results showed that the microbiome alpha diversity of the faecal, nasal and skin samples in HS patients was significantly lower when compared to 50 healthy controls (30 for faecal samples and 20 for nasal and skin swabs). Ruminococcus gnavus was more abundant in the faecal microbiome and an overabundance of Finegoldia magna was seen in the skin samples of HS patients compared to healthy controls.
Inflammatory Bowel Disease, Crohn’s disease & Ulcerative Colitis
Inflammatory Bowel Disease is a chronic inflammatory condition of the gastrointestinal tract with two main clinical manifestations; Crohn’s disease and Ulcerative Colitis. Crohn’s disease is a chronic inflammatory condition resulting in the inflammation of the digestive system. Ulcerative Colitis is a chronic condition resulting in the inflammation of the colon and rectum. It is estimated that 100 to 300 people in 100,000 people (as of 2020) suffer from Crohn’s and 156 to 291 people in 100,000 people (as of 2021) suffer from Ulcerative Colitis.
More research has been focused surrounding the role of an imbalance in the bacterial community in the gut and its role on Inflammatory Bowel Diseases. Environmental factors such as; gut microbial disbalance are one that is seen the most in Inflammatory Bowel Disease patients. Microbiome sequence showed a relative abundance of Ruminococcus gnavus in patients suffering from Inflammatory Bowel Diseases in comparison to healthy controls. In some severe cases, the Ruminococcus gnavus population was seen to be up to 69% of the gut microbiota, in comparison with a typical population being <0.1% of the gut microbiota. Inflammatory Bowel Disease patients also showed dramatic blooms of the overpopulation of Ruminococcus gnavus, particularly during disease activity. Two district clades of Ruminococcus gnavus strains were also identified, one of which is enriched in Inflammatory Bowel Disease patients. The study concluded that increased oxidative stress may be a major factor that shapes the disbalance of the microbiome in Inflammatory Bowel Disease patients and that Ruminococcus gnavus thrives in this altered imbalanced community.
Individual research into understanding the underlying cause, rather than targeting the individual symptoms, of Hidradenitis suppurativa, Inflammatory Bowel Disease; Crohn’s disease, and Ulcerative Colitis has revealed a common abundance of Ruminococcus gnavus population in patients’ gut microbiota. Whilst the most common therapeutic approaches to diminish the overgrowth of Ruminococcus gnavus in the gut would suggest a faecal transplant or long-term intake to personalized probiotics and prebiotics, to help balance out the microbial community in the gut. Whilst both approaches would have an effect on the gut microbiota, a third option is currently also put forward, phage therapy.
Unlike the faecal transplant and supplement intake, phage therapy is non-invasive and effective in a short amount of time, given that the correct natural lytic bacteriophages are selected for the therapy. Phage therapy also allows the use of a natural bacterial community assessor and predator to diminish the overgrowth of the Ruminococcus gnavus population, bringing it to a normal state, whilst giving the other members to increase their levels back to normal.