Does tormentil tincture (Tormentillae tinctura) support the therapy of leaky gut syndrome?

The leaky gut syndrome (LGS) is a combination of many disorders in the human body resulting from disturbance of the
intestinal barrier's selective permeability. Increased permeability enables penetration of undesirable particles, such as
toxins, outside the intestine lumen. These particles can be hazardous to health and may cause symptoms that reduce
the quality of life (e. g. flatulence, diarrhoea or constipation, vomiting, chronic fatigue, and headache). The cause of LGS
is unknown, but a significant impact of poor diet or lifestyle and infections of enteropathogens, especially
enterotoxigenic E. coli (ETEC), is suspected. The existing methods of therapy for the LGS are inefficient and insufficient.
Therefore, LGS is a subject over which numerous studies are conducted, and new approaches are sought.
Tormentillae rhizoma (TR) is a traditionally used pharmacopeial plant material with a wide range of applications mainly
related to gastrointestinal (GI) tract ailments. The herb originates from Tormentillae erecta (TE), from the Rosaceae
family, which is a widespread species in Eurasia. TR is taken orally in a form of decoctions and infusions, but the most
popular preparation is a tincture (Tormentillae tinctura (TT)). Orally, TR is used for the symptomatic treatment of
dysentery, diarrhoea, poisoning, ulcerative colitis, inflammation of GI.
TR has been used for centuries for treatment of GI tract infections, and its effectiveness has been clinically confirmed.
Despite attributed properties and observed bioactivity, the mechanisms responsible for the beneficial effects of TR in GI
tract ailments have not been yet fully determined. What is more, the chemical principles triggering biological effects are
not unambiguously indicated, especially that from a chemical perspective TR is a very interesting plant material
containing a wide variety of specialized metabolites, which can contribute to its therapeutic properties. What is more, as
medicine taken orally and with activity related to GI tract, its interaction with gut microbiota should be prioritized while
designing studies on its biological properties. The questions of Tormentillae tinctura metabolites (TTM) (TT constituents
metabolized by human gut microbiota) as well as its impact on microbiota homeostasis should be addressed. Despite
crucial role of intestinal epithelium and microbes residing in its lumen, there are no reports about the mechanism of
action of TT and interactions between TT and human gut environment.
In recent years, the significant contribution of gut microbiota in human organism homeostasis is observed. At first, the
microbiota is co-responsible for the intestinal barrier's selective permeability and is a source of Pathogen Associated
Molecular Patterns (PAMPs) migrating through the imbalanced epithelium, which then interact with hosts immune
system. Moreover, the bacteria present in the gut can convert orally taken compounds which can then be absorbed into
the bloodstream and interact with the biochemical processes. For this reason, the final properties of orally applied
preparations containing plant materials may differ from the properties of the compounds which are initially present in
them. On the other hand, orally applied therapeutics may alter the composition of human gut microbiota. The positive
outcome of this activity may include increasing the gut microbiota diversity and acting as probiotics, whereas the
negative outcome may be displayed as microbiome imbalance (dysbiosis). The negative impact on microbiota
communities can be observed in applied therapies of LGS, which are currently based on antibiotics and
chemotherapeutics and result in gut microbiota imbalance leading to significant long-term side effects.
The main aim of the submitted project is to justify the use of TT in the treatment of the leaky gut syndrome.
Hypotheses:
H1. TT contains condensed and hydrolyzable tannins contributing to its therapeutic properties.
H2. Chemical constituents of TT are metabolized by human gut microbiota and beneficially influence its diversity ex vivo.
H3. TT and TTM inhibit the growth of enterotoxigenic E. coli (ETEC) and Clostridium sp.
H4. TT and TTM influence the Caco-2 cells monolayers integrity and permeability parameters.
The studies to confirm the stated hypotheses will be carried out in cooperation between Microbiota Lab (Centre for
Preclinical Studies, Medical University of Warsaw and Institute of Animal Nutrition (Freie Universität Berlin).