biology Article Modulation of Stem Cell Progeny by Probiotics during Regeneration of Gastric Mucosal Erosions Farah Al-Yassir 1,2 , Ghalia Khoder 3, * , Subi Sugathan 1 , Prashanth Saseedharan 1 , Asma Al Menhali 4,5, * and Sherif M. Karam 1,5, *   Citation: Al-Yassir, F.; Khoder, G.; Sugathan, S.; Saseedharan, P.; Al Menhali, A.; Karam, S.M. Modulation of Stem Cell Progeny by Probiotics during Regeneration of Gastric Mucosal Erosions. Biology 2021, 10, 596. https://doi.org/10.3390/ biology10070596 Academic Editor: Walid Mottawea Received: 17 May 2021 Accepted: 25 June 2021 Published: 28 June 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain 17666, United Arab Emirates; fsa894@student.bau.edu.lb (F.A.-Y.); subisugathan@uaeu.ac.ae (S.S.); prash1987@hotmail.com (P.S.) 2 Department of Biological Sciences, Faculty of Science, Debbieh Campus, Beirut Arab University, P.O. Box 11-50-20 Riad El Solh 11072809, Beirut, Lebanon 3 Department of Pharmaceutics and Pharmaceutical Technology, Sharjah Institute for Medical Research, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates 4 Department of Biology, College of Science, United Arab Emirates University, Al Ain 15551, United Arab Emirates 5 Zayed Research Center for Health Sciences, United Arab Emirates University, Al Ain 17666, United Arab Emirates * Correspondence: gkhoder@sharjah.ac.ae (G.K.); asmaa@uaeu.ac.ae (A.A.M.); skaram@uaeu.ac.ae (S.M.K.); Tel.: +971-3-713-7493 (S.M.K.) Simple Summary: The wall of the stomach is easily damaged by different factors leading to serious diseases such as ulcers and cancer. In this study, the effects of a mixture of different types of beneficial bacteria (De Simone Formulation) were investigated in a mouse model of stomach wall damages induced by single or multiple doses of acetylsalicylic acid. Control mice received water. The stomachs of all mice were processed for microscopic examination and labeling of dividing stem cells and stomach cell lineages secreting mucus, acid, pepsin, and hormones. The results reveal beneficial effects for the multiple bacterial strain of De Simone Formulation given before or after the induction of stomach erosions. The regeneration of the stomach wall was associated with an increase in stem cell proliferation and enhanced production of protective factors such as mucus, and restoration of the aggressive factors produced by acid and pepsin secreting cell lineages. Therefore, the protective and therapeutic effects of the multi-strain healthy bacteria against stomach erosions involve modulation of not only dividing stem cells but also the multiple secretory cell lineages of the stomach. Abstract: Patients with gastric mucosal erosions are predisposed to chronic gastritis, ulcer or even can- cer. The repair of mucosal erosions involves several events including proliferation of gastric epithelial stem cells. The aim of this study was to investigate the effects of the probiotic mixture of De Simone Formulation on gastric epithelial stem cell lineages in mouse models of gastric mucosal erosions. Gas- tric erosions were induced by a single oral gavage of 80% ethanol containing 15 mg/mL acetylsalicylic acid (5 mL/kg) following a daily dose of probiotic mixture (5 mg/day/mouse) for 10 days. In another protocol, erosions were induced by a daily gavage of acetylsalicylic acid (400 mg/kg/day/mouse) for 5 days before or after daily administration of probiotic mixture for 5 days. Control mice received water gavage for 10 days. All mice were injected with bromodeoxyuridine two hours before sacrifice to label S-phase cells. The stomachs of all mice were processed for histological examination, lectin binding, and immunohistochemical analysis. The results reveal that mice that received probiotics before or after the induction of erosion showed a decrease in erosion index with an increase in gastric epithelial stem/progenitor cell proliferation and enhanced production of mucus, trefoil factors, and ghrelin by mucous and enteroendocrine cell lineages. These mice also showed restoration of the amount of H + ,K + -ATPase and pepsinogen involved in the production of the harsh acidic environ- ment by parietal and chief cell lineages. In conclusion, this study demonstrates the beneficial effects of probiotics against gastric mucosal erosion and highlights the involvement and modulation of proliferative stem cells and their multiple glandular epithelial cell lineages. Biology 2021, 10, 596. https://doi.org/10.3390/biology10070596 https://www.mdpi.com/journal/biology