Multi-Strain-Probiotic-Loaded Nanoparticles Reduced Colon Inflammation and Orchestrated the Expressions of Tight Junction, NLRP3 Inflammasome and Caspase-1 Genes in DSS-Induced Colitis Model

Abdullah Glil Alkushi; Sara T Elazab; Ahmed Abdelfattah-Hassan; Hala Mahfouz; Gamal A Salem; Nagwa I Sheraiba; Eman A A Mohamed; Mai S Attia; Eman S El-Shetry; Ayman A Saleh; Naser A ElSawy; Doaa Ibrahim

doi:10.3390/pharmaceutics14061183

Multi-Strain-Probiotic-Loaded Nanoparticles Reduced Colon Inflammation and Orchestrated the Expressions of Tight Junction, NLRP3 Inflammasome and Caspase-1 Genes in DSS-Induced Colitis Model

Pharmaceutics. 2022 May 31;14(6):1183. doi: 10.3390/pharmaceutics14061183.

Authors

Affiliations

¹ Department of Human Anatomy, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, Mecca 24382, Saudi Arabia.
² Department of Pharmacology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
³ Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt.
⁴ Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, October Gardens, 6th of October, Giza 12578, Egypt.
⁵ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
⁶ Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt.
⁷ Department of Husbandry and Animal Wealth Development, Faculty of Veterinary Medicine, University of Sadat City, Sadat 32897, Egypt.
⁸ Department of Microbiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt.
⁹ Zoology Department, Faculty of Science, Zagazig University, Zagazig 44511, Egypt.
¹⁰ Department of Human Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig 44511, Egypt.
¹¹ Department of Animal Wealth Development, Veterinary Genetics & Genetic Engineering, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt.
¹² Department of Anatomy & Embryology, Faculty of Medicine, Zagazig University, Zagazig 44511, Egypt.
¹³ Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt.

Abstract

Gut modulation by multi-strain probiotics (MSPs) is considered an effective strategy for treating inflammatory bowel disease (IBD). The combination of nanomaterial-based MSPs can improve their viability and resistance and can allow their targeted release in the gastrointestinal tract to be achieved. Thus, our aim is to investigate the prospective role of MSP integration into nanomaterials (MSPNPs) and the underlying molecular mechanisms supporting their application as an alternative therapy for IBD using a colitis rat model. To induce the colitis model, rats received 5% DSS, and the efficacy of disease progression after oral administration of MSPNPs was assessed by evaluating the severity of clinical signs, inflammatory response, expressions of tight-junction-related genes and NLRP3 inflammasome and caspase-1 genes, microbial composition and histopathological examination of colonic tissues. The oral administration of MSPNPs successfully alleviated the colonic damage induced by DSS as proved by the reduced severity of clinical signs and fecal calprotectin levels. Compared with the untreated DSS-induced control group, the high activities of colonic NO and MPO and serum CRP levels were prominently reduced in rats treated with MSPNPs. Of note, colonic inflammation in the group treated with MSPNPs was ameliorated by downstreaming NLRP3 inflammasome, caspase-1, IL-18 and IL-1β expressions. After colitis onset, treatment with MSPNPs was more effective than that with free MSPs in restoring the expressions of tight-junction-related genes (upregulation of occludin, ZO-1, JAM, MUC and FABP-2) and beneficial gut microbiota. Interestingly, treatment with MSPNPs accelerated the healing of intestinal epithelium as detected in histopathological findings. In conclusion, the incorporation of MPSs into nanomaterials is recommended as a perspective strategy to overcome the challenges they face and augment their therapeutic role for treating of colitis.

Keywords: NLRP3 inflammasome; colitis; histopathological examination; multi-strain probiotics; nanotherapy; tight junction.

Grants and funding

Supported by Umm Al-Qura University, project number (19-MED-1-01-0013).