An Exploratory Search for Potential Molecular Targets Responsive to the Probiotic Lactobacillus salivarius PS2 in Women With Mastitis: Gene Expression Profiling vs. Interindividual Variability

Abstract

Probiotics constitute an attractive alternative in the battle against microbial infections. Oral administration of certain strains of lactobacilli isolated from human milk has resulted in an effective reduction of the bacterial load as well as an improvement of the mastitis-associated symptoms. Nevertheless, little is yet known about the potential molecular mechanisms and specific targets implicated in these effects. Transcriptomic profiling has been used to search for disease-associated and therapy-responsive molecules in different disorders and experimental models. We have applied for the first time a gene expression-based molecular approach to explore for potential targets responsive to intervention with a probiotic in: (i) breast milk somatic cells (n = 17) and (ii) blood leukocytes (n = 19). Women with mastitis ingested a new strain of lactobacilli, Lactobacillus salivarius PS2 (3 × capsules per day, each capsule contained ~9.5 log10 CFU) for 21 days. We applied Affymetrix microarrays and Taqman one-step quantitative reverse transcription PCR (RT-qPCR) to analyze and compare gene expression changes between samples pre- and post-treatment. Our results substantiate the involvement of inflammatory and cell-growth related pathways and genes in the breast milk somatic cells following the intake of L. salivarius PS2. Individual analyses of selected genes: (1) supported the upregulation of STC1 and IL19 and the downregulation of PLAUR and IFNGR1 in the somatic cells of the patients as potential targets responsive to the probiotic, (2) detected a lack of a relationship between the gene expression responses in the two types of cells, and (3) evidenced a substantial interindividual variability in the gene expression changes in both types of cells. Our study provides an insight into the essentiality of incorporating the study of tissue-specific interindividual molecular responsivity into future clinical intervention trials to further understand the complexity of human gene expression responses to therapy and the potentiality of selecting appropriate responsive targets.

Sleep and Microbiome in Psychiatric Diseases

“…Nevertheless, to date transcriptomics-and metabolomics analyses before and after randomized, placebo-controlled, probiotics trials are to our best knowledge completely lacking in MDD, BD and psychotic disorders. There have only been a handful of studies carried out on healthy participants and patients with other medical disorders (e.g., autism, mastitis, inflammatory bowel diseases), which analyzed transcriptomics and metabolomics after probiotics trials [46][47][48][49][50][51].…”

Probiotics Dietary Supplementation for Modulating Endocrine and Fertility Microbiota Dysbiosis

“…In regard to the disorders and symptoms treated by probiotics, we found 4 articles about women suffering mastitis due to the presence of various causes including hormonal imbalances. All studies showed a significant improvement in the clinical status of the patient groups that received specific strains of Lactobacillus [21,23,31,32]. In the case of PCOS patients, one study administered Bifidobacterium lactis V9 to 14 patients and showed positive modulation capacities of sex hormone levels [33].…”

“…At this point, four studies had fulfilled the selection criteria and were reviewed thoroughly. The clinical trial designed by de Andrés et al [23] applied omics technologies to describe the interindividual variability of gene expression changes in somatic cells and blood leukocytes by the action of Lactobacillus salivarius PS2. The results demonstrated its modulating role in inflammatory and cell-grow only in the breast milk somatic cells.…”

“…These bacteria were selected by the previous demonstration of modulation of MG colonisation capacities and, consequently, colonisation of the infant's gut [72,73]. However, in the case of human clinical trials of mastitis, the predominant probiotic strains used are Lactobacillus salivarius PS2, L. salivarius CECT5713, L. gasseri CECT5714, L. fermentum CECT5716 [21][22][23]31,32], also the doses and period of administration were quite similar (3-4 weeks), with the exception of Fernández et al [32] in which study's period of administration lasted about 8 weeks. In all studies, the strains administered seem to be an efficient method for the treatment of mastitis and other hormonal imbalances triggering infections, as alternatives to antibiotics.…”

“…BV can be treated by the restauration of vaginal microbiota environment using probiotics. Most commonly used probiotics for modulating fertility dysbiosis include L. reuteri RC-14, L. fermentum, L. gasseri, L. rhamnosus, L. acidophilus, L. crispatus, L. casei, L. salivarius [20][21][22][23]. Clinical trials have shown that these probiotics can play a positive role in restoring vaginal microecology and treating BV [24].…”