GlobalCombination of probiotics, plant extracts and micronutrients shows positive effects on the integrity of the intestinal barrier
Dysbiosis causes functional gastrointestinal disorders
Multiple studies have shown that a dysbiosis of the intestinal microbiome is associated with various disorders or could even be the cause of such complaints. The following are examples [1]:
- Influence on intestinal motility
- Increased gas production
- Alteration of the gut-associated immune system
- Irritation/inflammation of the intestinal wall
- Damage to the intestinal barrier function
Combination of probiotics with plant extracts and micronutrients shows versatile bioactivity on FGID pathomechanisms
A) Pegaso® Enterodophilus® Baby (Colikind® drops), Schwabe Pharma, Italy [3, 4]:
| Quantities per daily dose | |
| Lactobacillus reuteri DSM 25175 | 1x109 CFU |
| Lactobacillus acidophilus DSM 24936 | 1x109 CFU |
| Chamomilla recutita L. oleolita (drug/extract ratio 1:2) | 5 mg |
| Native organic olive oil extra |
B) Pegaso® Enterodophilus® Junior, Schwabe Pharma, Italy [5]:
| Quantities per daily dose | |
| Lactobacillus reuteri DSM 25175 | 3x109 CFU |
| Lactobacillus acidophilus DSM 24936 | 3x109 CFU |
| Chamomilla recutita L. dry extract | 460 mg |
| of this, apigenin | 5.2 mg |
| FOS (fructooligosaccharides) | 37 mg |
| Vitamin A | 320 µg |
| Vitamin D | 5 µg |
Based on this model, transepithelial electrical resistance (TEER) and paracellular permeability are considered specific and sensitive biomarkers of intestinal barrier integrity and function. Lesions in the cell culture cause a drop in impedance in the TEER test. Treatment with inflammatory stimulants lowered the TEER compared to the untreated control, while pre-treatment with the study drug lowered the percentage resistance to a lesser extent. This resulted in a relative increase in TEER after pre-treatment with the drug complexes compared to the more reduced TEER of the control groups (see Tab. 1). These results were confirmed by determining the fluorescein isothyanate flux through the cell layer following the TEER experiment (see Fig. 1) [3–5].
Tab. 1. Effect of pre-treatment with the investigated complex on the transepithelial electrical resistance (TEER) after inflammatory stimulation.
| Test model | Result | References |
| CaCo-2 monolayer, pre-treatment with complex A, after 24 hours of inflammatory stimulation with LPS-conditioned THP-1 medium | After 3 and 6 hours, the pre-treatment resulted in a slight relative increase in TEER compared to the inflammatory stimulus of the control, p < 0.05 | [3] |
| CaCo-2 monolayer, pre-treatment with complex A, after 24 hours of inflammatory stimulation with LPS | At 21 and 24 hours, pre-treatment increased TEER by 11.43% and 7.78%, respectively, compared to the inflammatory stimulus of the control, p < 0.001 | [4] |
| CaCo-2 monolayer, pre-treatment with complex A, after 24 hours of inflammatory stimulation with INF-γ + TNF-α | After 24 hours, the pre-treatment increased the TEER significantly by 9.46% compared to the inflammatory stimulus of the control, p < 0.05 | [4] |
| CaCo-2 monolayer, pre-treatment with complex B, after 24 hours of inflammation stimulation with LPS | After 24 hours, pre-treatment increased TEER by 10.99% compared to the inflammatory stimulus of the control (personal information1), p < 0.05 | [5] |
CaCo: Colon carcinoma; LPS: Lipopolysaccharide; THP-1: Human monocytic cell line; INF: Interferon; TNF: Tumour necrosis factor
Fig. 1. Effect of pre-treatment with Pegaso® Enterodophilus® Junior (Ent J) on paracellular fluorescein isothyanate flux. A: without induction of inflammatory processes. B: with LPS-induced inflammatory processes. The horizontal dashed line marks the values of the control as 100%. The data are presented as a mean (± SEM) percentage of the basal fluorescence intensity of n = 3 experiments. *p < 0.05, ***p < 0.001 treatment vs. control [5]
Multimodal approach to the treatment of functional gastrointestinal disorders (FGIDs)
The multimodal mode of action of combinations of probiotics, herbal extracts and micronutrients can provide a fast-acting treatment option for FGIDs as well as a good alternative to a single probiotic [3–5]. Future studies based on this principle will clarify whether these combinations could be superior to a single strain of probiotics in the treatment of FGIDs. Chamomilla recutita extract possesses in vitro anti-inflammatory properties besides an antispasmodic and antidiarrhoeal potential and could thus contribute to the positive effect on typical FGID symptoms [6]. Olive oil polyphenols have anti-inflammatory and antioxidant properties which could have a positive effect on inflammatory mediators as well as on the protection of membrane permeability [7]. Vitamins A and D, as micronutrients, generally protect the mucous membranes and the integrity of the intestinal barrier [5].
1 Personal information from Dr Veronica Cocetta | Post Doc Researcher | University of Padova, Padova | UNIPD | Department of Pharmaceutical and Pharmacological Sciences DSF | Research profile (researchgate.net)
Literature
- Wei L et al. Gut microbiota dysbiosis in functional gastrointestinal disorders: Underpinning the symptoms and pathophysiology. JGH Open. 2021 Mar 23;5(9):976–987. doi: 10.1002/jgh3.12528. PMID: 34584964; PMCID: PMC8454481.
- Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features, and Rome IV. Section I: FGIDs: Background Information Functional GI Overview 2016;150(6):P1262–1279.e2, May 2016. doi: https://doi.org/10.1053/j.gastro.2016.02.032
- Borgonetti V et al. Anti-inflammatory activity of a fixed combination of probiotics and herbal extract in an in-vitro model of intestinal inflammation by stimulating Caco-2 cells with LPS-conditioned THP-1 cells medium. Minerva Pediatr (Torino). 2022;74(5):511–518. doi: 10.23736/S2724-5276.20.05765-5. Epub 2020 May 15. PMID: 32418407.
- Cocetta V et al. A Fixed Combination of Probiotics and Herbal Extracts Attenuates Intestinal Barrier Dysfunction from Inflammatory Stress in an In vitro Model Using Caco-2 Cells. Recent Pat Food Nutr Agric. 2019;10(1):62–69. doi: 10.2174/2212798410666180808121328. PMID: 30088455.
- Cocetta V, Giacomini I, Tinazzi M, Berretta M, Quagliariello V, Maurea N, Ragazzi E, Carnevali I, Montopoli M. Maintenance of intestinal epithelial barrier integrity by a combination of probiotics, herbal extract, and vitamins. Minerva Pediatr (Torino). 2023 May 11. doi: 10.23736/S2724-5276.23.07128-8. Epub ahead of print. PMID: 37166776.
- Mehmood MH, Munir S, Khalid UA, Asrar M, Gilani AH. Antidiarrhoeal, antisecretory and antispasmodic activities of Matricaria chamomilla are mediated predominantly through K(+)-channels activation. BMC Complement Altern Med. 2015;15:75. doi: 10.1186/s12906-015-0595-6. PMID: 25886126; PMCID: PMC4410481.
- Deshpande GC, Cai W. Use of Lipids in Neonates Requiring Parenteral Nutrition. JPEN J Parenter Enteral Nutr. 2020;44(Suppl 1):S45–S54. doi: 10.1002/jpen.1759. PMID: 32049399.
Conflicts of interest: S. Barth is an employee at Dr. Willmar Schwabe GmbH & Co. KG. G. Bulferi, R. Lanza, H. De Togni, F. Raso are employees at SCHWABE PHARMA ITALIA SRL.
Disclosure: The writing and publication of this article is funded by Dr. Willmar Schwabe GmbH & Co. KG, Willmar-Schwabe-Str. 4, 76227 Karlsruhe, Germany.
