Unlocking the Potential of Probiotics: A Comprehensive Review on Research, Production, and Regulation of Probiotics.

This review provides a comprehensive overview of the current state of probiotic research, covering a wide range of topics, including strain identification, functional characterization, preclinical and clinical evaluations, mechanisms of action, therapeutic applications, manufacturing considerations, and future directions. The screening process for potential probiotics involves phenotypic and genomic analysis to identify strains with health-promoting properties while excluding those with any factor that could be harmful to the host. In vitro assays for evaluating probiotic traits such as acid tolerance, bile metabolism, adhesion properties, and antimicrobial effects are described. The review highlights promising findings from in vivo studies on probiotic mitigation of inflammatory bowel diseases, chemotherapy-induced mucositis, dysbiosis, obesity, diabetes, and bone health, primarily through immunomodulation and modulation of the local microbiota in human and animal models. Clinical studies demonstrating beneficial modulation of metabolic diseases and human central nervous system function are also presented. Manufacturing processes significantly impact the growth, viability, and properties of probiotics, and the composition of the product matrix and supplementation with prebiotics or other strains can modify their effects. The lack of regulatory oversight raises concerns about the quality, safety, and labeling accuracy of commercial probiotics, particularly for vulnerable populations. Advancements in multi-omics approaches, especially probiogenomics, will provide a deeper understanding of the mechanisms behind probiotic functionality, allowing for personalized and targeted probiotic therapies. However, it is crucial to simultaneously focus on improving manufacturing practices, implementing quality control standards, and establishing regulatory oversight to ensure the safety and efficacy of probiotic products in the face of increasing therapeutic applications.

Synergistic synbiotic containing fructooligosaccharides and Lactobacillus delbrueckii CIDCA 133 alleviates chemotherapy-induced intestinal mucositis in mice.

Intestinal mucositis is a commonly reported side effect in oncology patients undergoing chemotherapy and radiotherapy. Probiotics, prebiotics, and synbiotics have been investigated as alternative therapeutic approaches against intestinal mucositis due to their well-known anti-inflammatory properties and health benefits to the host. Previous studies showed that the potential probiotic Lactobacillus delbrueckii CIDCA 133 and the prebiotic Fructooligosaccharides (FOS) alleviated the 5-Fluorouracil (5-FU) chemotherapy-induced intestinal mucosa damage. Based on these previous beneficial effects, this work evaluated the anti-inflammatory property of the synbiotic formulation containing L. delbrueckii CIDCA 133 and FOS in mice intestinal mucosa inflammation induced by 5-FU. This work showed that the synbiotic formulation was able to modulate inflammatory parameters, including reduction of cellular inflammatory infiltration, gene expression downregulation of Tlr2, Nfkb1, and Tnf, and upregulation of the immunoregulatory Il10 cytokine, thus protecting the intestinal mucosa from epithelial damage caused by the 5-FU. The synbiotic also improved the epithelial barrier function by upregulating mRNA transcript levels of the short chain fatty acid (SCFA)-associated GPR43 receptor and the occludin tight junction protein, with the subsequent reduction of paracellular intestinal permeability. The data obtained showed that this synbiotic formulation could be a promising adjuvant treatment to be explored against inflammatory damage caused by 5-FU chemotherapy.

Paraprobiotics and Postbiotics of Lactobacillus delbrueckii CIDCA 133 Mitigate 5-FU-Induced Intestinal Inflammation.

Intestinal mucositis is a commonly reported side effect in oncology practice. Probiotics are considered an excellent alternative therapeutic approach to this debilitating condition; however, there are safety questions regarding the viable consumption of probiotics in clinical practice due to the risks of systemic infections, especially in immune-compromised patients. The use of heat-killed or cell-free supernatants derived from probiotic strains has been evaluated to minimize these adverse effects. Thus, this work evaluated the anti-inflammatory properties of paraprobiotics (heat-killed) and postbiotics (cell-free supernatant) of the probiotic Lactobacillus delbrueckii CIDCA 133 strain in a mouse model of 5-Fluorouracil drug-induced mucositis. Administration of paraprobiotics and postbiotics reduced the neutrophil cells infiltrating into the small intestinal mucosa and ameliorated the intestinal epithelium architecture damaged by 5-FU. These ameliorative effects were associated with a downregulation of inflammatory markers (Tlr2, Nfkb1, Il12, Il17a, Il1b, Tnf), and upregulation of immunoregulatory Il10 cytokine and the epithelial barrier markers Ocln, Cldn1, 2, 5, Hp and Muc2. Thus, heat-killed L. delbrueckii CIDCA 133 and supernatants derived from this strain were shown to be effective in reducing 5-FU-induced inflammatory damage, demonstrating them to be an alternative approach to the problems arising from the use of live beneficial microorganisms in clinical practice.

Probiotics, Prebiotics, Synbiotics, and Paraprobiotics as a Therapeutic Alternative for Intestinal Mucositis.

Intestinal mucositis, a cytotoxic side effect of the antineoplastic drug 5-fluorouracil (5-FU), is characterized by ulceration, inflammation, diarrhea, and intense abdominal pain, making it an important issue for clinical medicine. Given the seriousness of the problem, therapeutic alternatives have been sought as a means to ameliorate, prevent, and treat this condition. Among the alternatives available to address this side effect of treatment with 5-FU, the most promising has been the use of probiotics, prebiotics, synbiotics, and paraprobiotics. This review addresses the administration of these "biotics" as a therapeutic alternative for intestinal mucositis caused by 5-FU. It describes the effects and benefits related to their use as well as their potential for patient care.