LACTICASEIBACILLUS PARACASEI DSM 34154 (L. CASEI DG®) IN PRECLINICAL AND CLINICAL STUDIES AND ITS GENETIC STABILITY OVER A DECADE OF INDUSTRIAL PRODUCTION

Lacticaseibacillus paracasei DSM 34154, commercially known as L. casei DG® (LC-DG), served as the fil rouge of the whole PhD thesis, which investigates its genetic stability over a decade of industrial biomass production, as well as its effects in preclinical and clinical studies. LC-DG, a well-characterized probiotic strain, has been included in the dietary supplement Enterolactis® on the market for over 20 years because of its proven health benefits. This PhD project initially examined the genetic stability of LC-DG across various industrial production batches through comparative genomic analysis at the single nucleotide level. The findings demonstrate that LC-DG maintains substantial genetic and phenotypic equivalence across all examined lots, effectively mitigating the risk of genetic drift that could compromise probiotic properties. These results highlight the effectiveness of current industrial production practices in preserving the genetic integrity of LC-DG, assuring both producers and consumers that its health benefits are maintained over time, thereby ensuring product reliability. Further preclinical evaluations emphasize LC-DG's ability to effectively survive gastrointestinal transit (GIT) and modulate host immune responses. Then, in vitro studies conducted in a human intestinal cell line model on the AminoAltaTM probiotic formulation (AApf), which combines L. casei DG® with another Lacticaseibacillus paracasei strain, have demonstrated LC-DG's ability to reduce reactive oxygen species (ROS), exhibit anti-inflammatory properties, stimulate macrophage activity, adhere to the differentiated cell layer, and maintain the integrity of the epithelial barrier. These beneficial effects of probiotic supplementation could be crucial in protecting athletes from the physiological stress caused by intense physical activity. The subsequent clinical study (ESA-19) investigated LC-DG's therapeutic potential for treating irritable bowel syndrome (IBS). In this pilot, multicenter, randomized, double-blind, cross-over, placebo-controlled study, the administration of Enterolactis® Ultra significantly influenced the intestinal microbial ecosystem in non-constipated IBS patients, notably by altering short-chain fatty acids (SCFAs) relative proportion, indicating its potential role in alleviating IBS symptoms. This study also highlights the need to identify predictive biomarkers for tailoring personalized probiotic management strategies. Overall, the results of this PhD thesis enhance our understanding of LC-DG, reinforcing the quality, efficacy, and reliability of the probiotic products containing this strain and ensuring that health benefits can be consistently provided to consumers over time.

Grantor dc:publisher

Università degli Studi di Milano

Year dc:date

2024

Author dc:creator

• BRUNELLI, LAURA

Contributors dc:contributor

• tutor: S. Guglielmetti ; co-tutor: W. Fiore ; coordinatore: D. Mora
• L. Brunelli
• MORA, DIEGO

• Lacticaseibacillus paracasei
• preclinical
• clinical
• genetic stability
• industrial biomass production

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Handle dc:identifier

https://hdl.handle.net/2434/1119132

OAI identifier oai:identifier

oai:air.unimi.it:2434/1119132