Functional dyspepsia is a common and highly prevalent gastrointestinal disorder defined by upper abdominal symptoms, which can manifest both chronically and in isolated incidents in individuals. While functional dyspepsia has no organic explanation on routine investigations, recent evidence indicated local duodenal and systemic changes.

The exact causes of functional dyspepsia are still unknown, but evidence suggests that its pathophysiology may involve an altered gut-brain interaction, changes in gut microbiota composition and/or function, altered mucosal immune function, visceral hypersensitivity and abnormal gastrointestinal motility. That explains why the condition and others such as irritable bowel syndrome, formerly known as functional gastrointestinal disorders, have been renamed as disorders of gut-brain interaction.

As the first line treatment of functional dyspepsia with proton-pump inhibitors can show safety issues that include an altered gut microbiome, potential benefits of probiotics for balancing the gut microbiota have been suggested.

A new randomized, double-blind, placebo-controlled trial has shown that treatment with a spore-forming probiotic combining Bacillus coagulans MY01 and B. subtilis MY02 strains is effective and safe in adult patients with functional dyspepsia, compared with placebo.

The probiotic treatment consisted of a combination of B. coagulans MY01 and B. subtilis MY02 strains (2.5 x 109 colony-forming units per capsule) with 300 mg of maltodextrin prebiotic administered twice per day for 8 weeks (probiotic group; n=32) compared with maltodextrin (placebo group; n=36). That was followed by an additional phase of 8 weeks consisting of treatment with probiotics (non-randomized, non-controlled trial phase).

The efficacy of the spore-forming probiotic was associated with changes in Th17 immune signaling and fecal microbiota composition

Symptom benefits were reported by the end of the 8 weeks, measured by a decrease in postprandial distress syndrome score of 0.7 or greater and epigastric pain syndrome score in participants in the probiotic group compared to placebo, regardless of whether patients consumed proton-pump inhibitors or not. Moreover, in patients with functional dyspepsia on proton-pump inhibitors, the benefits of the probiotic included a reduction in small intestinal bacterial overgrowth after 8 weeks.

The efficacy of the spore-forming probiotic was associated with changes in Th17 immune signaling and fecal microbiota composition.

After an 8-week open-label extension, the treatment with the spore-forming probiotic reduced circulating IL-17A and decreased proportions of Th17 cells, which are considered to be systemic immune markers involved in bacterial and fungal host responses. Previous animal findings have shown the ability of B. subtilis to shift Th17 to regulatory T cell (Treg) responses and the involvement of B. coagulans in increasing the proportion of Tregs. An additional immune mechanism of spore-forming probiotics in patients with functional dyspepsia on proton-pump inhibitors was shown in a decrease in Th2 signaling and gut-homing T cells.

The results suggest that the increase in the proportion of Tregs is a mechanism by which spore-forming probiotics may benefit patients with functional dyspepsia, where immune activation has been involved in the condition’s origin.

Immune changes were also accompanied by an increase in the fecal abundance of Faecalibacterium and Roseburia, which are both butyrate producers. That could be as a result of interactions with other gut commensals or Bacillus species in the probiotic, but also secondary to maltodextrin stimulation. However, only Faecalibacterium was associated with probiotic efficacy.

On the whole, the findings suggest that spore-forming probiotics could be an effective and well-tolerated option in patients with functional dyspepsia through changes in systemic immune activation and gut microbiota composition. The mechanisms of action by which spore-forming probiotics can help in managing functional dyspepsia deserve further research, as do both efficacy and safety in the long term.

 

References:

Black CJ, Drossman DA, Talley NJ, et al. Functional gastrointestinal disorders: advances in understanding and management. Lancet. 2020; 396(10263):1664-1674. doi: 10.1016/S0140-6736(20)32115-2.

Wauters L, Slaets H, De Paepe K, et al. Efficacy and safety of spore-forming probiotics in the treatment of functional dyspepsia: a pilot randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2021; 6(10):784-792. doi: 10.1016/S2468-1253(21)00226-0.