Ruminococcus bromii alleviates constipation by pullulanase-driven resistant starch degradation and microbiota modulation.

The genus Ruminococcus was depleted in constipated patients compared to healthy controls.

• Analysis of gut microbiota composition identified Ruminococcus as a key genus reduced in constipated patients.
• This finding motivated testing of four Ruminococcus species: R. bromii, R. torques, R. obeum, and R. gnavus.
• The depletion of Ruminococcus was identified through bioinformatic analysis of patient microbiota data.

All four tested Ruminococcus species (R. bromii, R. torques, R. obeum, and R. gnavus) alleviated constipation symptoms in constipated mice.

• The four species were tested in a constipated mouse model.
• All four species demonstrated constipation-relieving effects.
• R. bromii was identified as the most effective of the four species tested.

R. bromii's pullulanase enzyme was identified as the key mechanism for degrading resistant starch.

• Pullulanase is an enzyme produced by R. bromii that drives resistant starch degradation.
• This enzymatic activity was identified as the primary mechanism underlying R. bromii's constipation-relieving effects.
• Pullulanase-driven resistant starch degradation distinguished R. bromii as the most effective species among those tested.

R. bromii-mediated resistant starch degradation boosted short-chain fatty acid (SCFA) production and fostered growth of beneficial bacteria.

• Resistant starch degradation by R. bromii led to increased short-chain fatty acid production.
• Beneficial bacteria including Akkermansia and Bifidobacterium were enriched following R. bromii activity.
• The microbiota modulation represents a downstream effect of R. bromii's enzymatic activity on resistant starch.

A clinical trial confirmed that the constipation-relieving effect of dietary resistant starch was dependent on the presence and abundance of R. bromii in the gut.

• A subsequent clinical trial was conducted to validate findings from mouse experiments.
• The efficacy of dietary resistant starch as a constipation intervention was contingent on R. bromii presence in the gut.
• Both the presence and abundance of R. bromii were identified as factors determining the response to dietary resistant starch.
• This finding positions R. bromii as a key microbial mediator for the dietary fiber-constipation relief relationship.

R. bromii is positioned as a promising candidate for targeted probiotic or synbiotic therapies for constipation.

• The study identifies R. bromii as a key microbial mediator for constipation relief through resistant starch metabolism.
• The synbiotic approach would combine R. bromii (probiotic) with resistant starch (prebiotic substrate).
• The clinical trial validation supports the translational potential of R. bromii-based interventions.