Mechanism of Action
Holigos™ IBS contains glycans identical to those in human milk and the mucus layer of the GI tract
The glycans in Holigos™ IBS play a critical, multi-functional role in promoting and maintaining good gastrointestinal development and health. For example, in infants1, they:
- Modulate the microbiota to increase bifidobacteria, prevent pathogen attachment, and reduce proteolytic bacteria that impair the mucus layer
- Moderate nociceptive stimuli to reduce abdominal pain and colic
- Increase production of short-chain fatty acids that are key to gut barrier function
- Modulate gene expression in epithelial cells to increase mucin production
- Regulate and develop the immune response at the gut barrier level
In IBS patients, Holigos TM IBS drives towards intestinal homeostasis through 3 core mechanisms
1. Holigos™ IBS specifically modulates the intrinsic intestinal microbiota, improving microbial metabolites, including short chain fatty acids and bile acids
At least a subset of IBS patients has an abnormal microbiota composition and particularly a reduction in bifidobacteria12. This is associated with symptoms13 including abdominal pain14. Intestinal models show that Holigos™ impacts the gut microbiota in various sections of the intestine, balancing the composition by stimulating the growth of beneficial bacteria such as bifidobacteria15,16. Also, clinical studies in healthy children, healthy adults and IBS patients (all subtypes) show that Holigos™ beneficially modulates the microbiota and increases bifidobacteria. No foreign bacteria are introduced; the glycans in Holigos™ IBS modulate the patient’s intrinsic microbiota.
Importantly, if the intestinal microbiota is out of balance, metabolites produced by the bacteria are likely to be out of balance. These metabolites include short chain fatty acids, essential vitamins, bile acids and neuromodulators. Impaired bile acid metabolism has been observed in IBS patients17. Normally primary bile acids in the colon are converted by certain bacteria to secondary bile acids. However, this may be impaired in IBS patients where a higher concentrations of primary bile acids have been measured compared to healthy controls and this has been correlated with abdominal pain and frequency of stool evacuation17,18. Holigos™ has been shown to decrease primary bile acids in an in vitro gut model simulating an imbalanced microbiota as compared to control19.
2. Holigos™ IBS improves the gut barrier function of IBS patients by increasing the production of nutrients critical for epithelial cells
The gut microbiota is a source of an extensive array of nutrients critical for host health20. Key among these nutrients are short chain fatty acids (SCFAs) which arise from the bacterial fermentation of dietary fibers. The SCFA butyrate is the primary fuel for intestinal epithelial cells and SCFAs in general help maintain immune homeostasis21, making SCFAs essential for gut barrier functioning. Impaired gut barrier functioning (“leaky gut”) is common in many IBS patient and SCFAs have been suggested as a potential diagnostic marker of IBS22. Holigos™ improves the profile of bacterial metabolites, increasing the concentration of SCFAs specifically butyrate and acetate, and decreasing detrimental metabolites14,15. This improvement of bacterial metabolites impacts gut barrier functioning by decreasing intestinal permeability23.
3. Holigos TM IBS modulates the mucosal immune system, driving it towards homeostasis
The mucosal immune system may be unbalanced in at least a subset of IBS patients. This may be due to interactions between a dysbiotic microbiota and the mucosal immune system24, or due to an impaired gut barrier24. In addition, associations between the mucosal immune system and clinical symptoms have been found25,26. By beneficially modulating the intestinal microbiota and improving gut barrier function, Holigos™ IBS modulates the mucosal immune system and drives it towards homeostasis27,28.