Safety Evaluation of Lactobacillus delbrueckii subsp. lactis CIDCA 133: a Health-Promoting Bacteria

Jesus, Luís Cláudio Lima de; Sousa, Thiago de Jesus; Coelho-Rocha, Nina Dias; Profeta, Rodrigo; Barroso, Fernanda Alvarenga Lima; Drumond, Mariana Martins; Mancha-Agresti, Pamela; Ferreira, Ênio; Brenig, Bertram; Aburjaile, Flávia Figueira; Azevedo, Vasco

doi:10.1007/s12602-021-09826-z

Cited by 14 publications

(8 citation statements)

References 87 publications

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“…Based on this information, we suggest that CIDCA 133 can upregulated mucin 2 as a mechanism to control the dysbiotic microbiota and maintain intestinal homeostasis. Altogether, these above mechanisms may lead to translocation inhibition of pathogenic microorganisms and toxins into the lamina propria, thereby attenuating an exacerbated inflammatory response ( Sonis, 2004 ; Krishna Rao and Samak, 2013 ; Maioli et al, 2014 ), and, thus, reinforcing the importance of this strain in maintaining the epithelial barrier, as previously demonstrated by de Jesus et al (2019) and de Jesus et al (2021a) .…”

Section: Discussionmentioning

confidence: 62%

“…One of our pioneering studies showed that a fermented milk formulation containing L. delbrueckii CIDCA 133 could attenuate antineoplastic 5-FU-induced intestinal epithelial tissue disruption by inhibiting degeneration of goblet cells, intestinal permeability, and inflammatory cell infiltration ( de Jesus et al, 2019 ). In our other studies, we reported that no adverse effect was observed in healthy BALB/c mice after CIDCA 133 consumption, but its consumption stimulated the mucosal immune system and epithelial barrier by upregulating the gene expression of tight junction protein occludin ( Ocln ) ( de Jesus et al, 2021a ), anti-inflammatory cytokines ( Il10 and Tgfb1 ) and mucin 2 ( Muc2) , and inhibiting the proinflammatory transcription factor Nfkb1 (p105) ( de Jesus et al, 2021b ). In this context, this study investigated whether the modulation of inflammatory and epithelial barrier biomarkers by Lactobacillus delbrueckii CIDCA 133 would be associated with its beneficial effects against 5-FU chemotherapy-induced intestinal mucositis.…”

Section: Introductionmentioning

confidence: 99%

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Lactobacillus delbrueckii CIDCA 133 Ameliorates Chemotherapy-Induced Mucositis by Modulating Epithelial Barrier and TLR2/4/Myd88/NF-κB Signaling Pathway

et al. 2022

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Intestinal mucositis promoted by the use of anticancer drugs is characterized by ulcerative inflammation of the intestinal mucosa, a debilitating side effect in cancer patients undergoing treatment. Probiotics are a potential therapeutic option to alleviate intestinal mucositis due to their effects on epithelial barrier integrity and anti-inflammatory modulation. This study investigated the health-promoting impact of Lactobacillus delbrueckii CIDCA 133 in modulating inflammatory and epithelial barrier markers to protect the intestinal mucosa from 5-fluorouracil-induced epithelial damage. L. delbrueckii CIDCA 133 consumption ameliorated small intestine shortening, inflammatory cell infiltration, intestinal permeability, villus atrophy, and goblet cell count, improving the intestinal mucosa architecture and its function in treated mice. Upregulation of Muc2, Cldn1, Hp, F11r, and Il10, and downregulation of markers involved in NF-κB signaling pathway activation (Tlr2, Tlr4, Nfkb1, Il6, and Il1b) were observed at the mRNA level. This work suggests a beneficial role of L. delbrueckii strain CIDCA 133 on intestinal damage induced by 5-FU chemotherapy through modulation of inflammatory pathways and improvement of epithelial barrier function.

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Section: Discussionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Lactobacillus delbrueckii CIDCA 133 Ameliorates Chemotherapy-Induced Mucositis by Modulating Epithelial Barrier and TLR2/4/Myd88/NF-κB Signaling Pathway

et al. 2022

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“…Additionally, a probiogenomics study of this strain showed that its anti-inflammatory profile could be related to genes encoding secreted and membrane surface proteins able to interact with immune proteins involved in the NF-κB signaling pathway [ 31 ]. Regarding its safety concerns, it was reported that CIDCA 133 (10 7 CFU/mL) did not cause blood hemolysis, mucin degradation, or epithelial damage in healthy mice, evidencing that this strain presents safety levels for probiotic application [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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“…Some studies have been characterizing the L. delbrueckii strains as probiotics based on their ability to resist gastrointestinal tract (GIT) stressors ( Ferreira et al, 2013 ), pathogens inhibition ( De Jesus L. C. L. et al, 2021 ), and anti-inflammatory effects mainly focused on GIT disease treatment, such as colorectal cancer ( Wan et al, 2014 ), ulcerative colitis ( Santos Rocha et al, 2014 ), and intestinal mucositis ( De Jesus et al, 2019 ). In addition, pre-clinical therapeutical applications of these microorganisms to other pathological conditions, such as arthritis ( Kano et al, 2013 ), depression ( Qiu et al, 2021 ), and diabetes ( Hallajzadeh et al, 2021 ), have also been reported.…”

Section: Introductionmentioning

confidence: 99%

“…Among this species, L. delbrueckii subsp. lactis CIDCA 133 is the best-characterized probiotics strain whose beneficial characteristics and safety aspects have been widely evaluated by in vitro and in vivo , as well as in silico analysis, for example, its ability to inhibit Escherichia coli , Bacillus cereus , Citrobacter rodentium , and Salmonella Typhimurium pathogens; immunomodulation by inhibition of NF-κB signaling pathway; tolerance to high concentrations of bile salts; no hemolytic or mucin degradation activity, and no adverse effects to clinical and histopathological mice parameters ( Rolny et al, 2016 ; Hugo et al, 2017 ; De Jesus et al, 2019 ; De Jesus L. C. L. et al, 2021 ; De Jesus LCL. et al, 2021 ; Barroso et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Genomic Characterization of Lactobacillus delbrueckii Strains with Probiotics Properties

et al. 2022

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Probiotics are health-beneficial microorganisms with mainly immunomodulatory and anti-inflammatory properties. Lactobacillus delbrueckii species is a common bacteria used in the dairy industry, and their benefits to hosting health have been reported. This study analyzed the core genome of nine strains of L. delbrueckii species with documented probiotic properties, focusing on genes related to their host health benefits. For this, a combined methodology including several software and databases (BPGA, SPAAN, BAGEL4, BioCyc, KEEG, and InterSPPI) was used to predict the most important characteristics related to L. delbrueckii strains probiose. Comparative genomics analyses revealed that L. delbrueckii probiotic strains shared essential genes related to acid and bile stress response and antimicrobial activity. Other standard features shared by these strains are surface layer proteins and extracellular proteins-encoding genes, with high adhesion profiles that interacted with human proteins of the inflammatory signaling pathways (TLR2/4-MAPK, TLR2/4-NF-κB, and NOD-like receptors). Among these, the PrtB serine protease appears to be a strong candidate responsible for the anti-inflammatory properties reported for these strains. Furthermore, genes with high proteolytic and metabolic activity able to produce beneficial metabolites, such as acetate, bioactive peptides, and B-complex vitamins were also identified. These findings suggest that these proteins can be essential in biological mechanisms related to probiotics’ beneficial effects of these strains in the host.

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Safety Evaluation of Lactobacillus delbrueckii subsp. lactis CIDCA 133: a Health-Promoting Bacteria

Cited by 14 publications

References 87 publications

Lactobacillus delbrueckii CIDCA 133 Ameliorates Chemotherapy-Induced Mucositis by Modulating Epithelial Barrier and TLR2/4/Myd88/NF-κB Signaling Pathway

Lactobacillus delbrueckii CIDCA 133 Ameliorates Chemotherapy-Induced Mucositis by Modulating Epithelial Barrier and TLR2/4/Myd88/NF-κB Signaling Pathway

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

Genomic Characterization of Lactobacillus delbrueckii Strains with Probiotics Properties

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