03/27/2025
By Danielle Fretwell
The Francis College of Engineering, Department of Biomedical Engineering, invites you to attend a Doctoral Dissertation Proposal defense by Grace Callen on: "Investigating Probiotic Treatment Efficacy Within a Physiologically Relevant Oral Tissue Model."
Date: Tuesday, April 8, 2025
Time: 1:30 - 3:30 p.m.
Location: Perry 210
Committee:
Advisor: Chiara Ghezzi, Ph.D., Department of Biomedical Engineering, UMass Lowell
Committee Members*
Bryan Black, Ph.D., Department of Biomedical Engineering, UMass Lowell
Carl Lawton, Ph.D., Department of Chemical Engineering, UMass Lowell
Shannon Kelleher, Ph.D., Department of Biomedical and Nutritional Sciences, UMass Lowell
Abstract:
Gingivitis is the most prevalent oral disease, a reversible state of gum inflammation that affects an estimated 46% of adults and is the precursor for more severe, non-reversible periodontitis. Although the trajectory of the disease is not fully understood, it is known that initial events stem from dysbiosis between the host and oral microbiome. In recent years, probiotics have been of significant interest as a potential noninvasive treatment for gingivitis and periodontitis. Probiotics are live microorganisms crucial in supporting the host and the microbiome by maintaining eubiosis amongst microbial communities. While there is a consensus on the beneficial impact of probiotics in periodontal health, the lack of a standardized way to compare experimental results across in vitro, in vivo, and clinical studies has led to varying results and hindered the clinical indication of probiotics for treating oral diseases. Consequently, there is a need for high-throughput in vitro studies are essential to elucidate probiotics' effects on the oral microbiome and assess their potential as targeted therapeutic agents. We have developed a humanized and physiologically relevant anatomical gingival tissue model to improve the current understanding of periodontitis. Our previous work has validated the model’s ability to accurately reflect the cytoarchitecture of the oral gingiva and the initial inflammatory response reported in periodontal disease. Additionally, the in vitro model has shown the potential to maintain an inoculated host microbiome's complex structure and composition.
I propose an investigation of host and microbiome responses of the OTM to a probiotic mouthwash treatment (PMT). I aim to advance the field of oral microbiome research and gain extensive training through harnessing advanced in vitro modeling techniques to rigorously interrogate the mechanistic underpinnings and therapeutic potential of probiotic treatments. To investigate probiotics’ effect on the oral microbiome within the OTM, we designed a probiotic mouthwash treatment (PMT) in accordance with clinical study regimes, consisting of a homogenous resuspension of Lactobacillus rhamnosus and Bifidobacterium longum in phosphate-buffered saline (PBS 1x). With this, the project will be carried out based on the following aims: 1) Validate and characterize OTM (host) response to probiotic treatment; and 2) Underscore the effect of PMT on inoculated oral microbiome. By accomplishing the following aims, I will further understand the: i) Role of oral architecture in the different stages of oral dysbiosis; ii) How probiotic treatment affects microbiota biogeography, organization and polymicrobial communities’ progression toward pathogenicity; as well as iii) The effectiveness of probiotic treatment in the reversal of gingivitis conditions. Preliminary data (picoGreen, lactate dehydrogenase, and immunohistochemistry) indicated that after receiving PMT, a fully viable, differentiated, stratified epithelium and viable OTM formed. In future studies carried out through Aim 2, the model will be exposed to patient-derived microbiomes (healthy versus gingivitis clinical conditions) to study host-microbiome interactions. This work offers a robust platform to produce standardized in vitro study data on the efficacy of probiotics as a treatment for gingivitis as a valid comparator to clinical trial results. Beyond oral health, these insights could advance our broader understanding of host-microbe interactions, inform the development of precision probiotics, and contribute to microbiome-based therapeutic strategies.