Bifidobacterium is a predominant and important genus in the bacterial population of the human gut microbiota. Despite the increasing number of studies on the beneficial functionality of bifidobacteria for human health, knowledge about their antioxidant potential is still insufficient. Several in vivo and in vitro studies of Bifidobacterium strains and their cellular components have shown good antioxidant capacity that provided a certain protection of their own and the host’s cells. Our work presents the data of transcriptomic, proteomic, and metabolomic analyses of the growing and stationary culture of the probiotic strain B. longum subsp. longum GT15 after exposure to hydrogen peroxide for 2 h and oxygen for 2 and 4 h. The results of the analysis of the sequenced genome of B. longum GT15 showed the presence of 16 gene-encoding proteins with known antioxidant functions. The results of the full transcriptomic analysis demonstrated a more than two-fold increase of levels of transcripts for eleven genes, encoding proteins with antioxidant functions. Proteomic data analysis showed an increased level of more than two times for glutaredoxin and thioredoxin after the exposure to oxygen, which indicates that the thioredoxin-dependent antioxidant system may be the major redox homeostasis system in B. longum bacteria. We also found that the levels of proteins presumably involved in global stress, amino acid metabolism, nucleotide and carbohydrate metabolism, and transport had significantly increased in response to oxidative stress. The metabolic fingerprint analysis also showed good discrimination between cells responding to oxidative stress and the untreated controls. Our results provide a greater understanding of the mechanism of oxidative stress response in B. longum and the factors that contribute to its survival in functional food products.

Since there is currently no cure for Parkinson’s disease, pharmacobiotic approaches based on gut microbiota—capable of producing pharmacologically active compounds—are under development. In this study, we propose LfU21, derived from the strain Limosilactobacillus fermentum U-21, as a candidate pharmacobiotic. To evaluate its efficacy, a combined LPS- and lactacystin (LAC)-induced Parkinson’s disease model was established in Wistar rats. Effects were assessed using behavioral, biochemical, immunomodulatory, and transcriptomic biomarkers. LfU21 administration reduced α-synuclein levels, altered motor performance in the “Rung ladder” test, and modulated bdnf gene expression in the right and left striata. Under LPS exposure, LfU21 prevented alterations in immune response markers, GSH levels, drd2 and bdnf gene expression, and intestinal goblet cell counts. In LAC and LAC + LPS groups, LfU21 mitigated the rise in α-synuclein, the decline in bdnf expression, and behavioral deficits in the “Open Field” and “Rung ladder” tests, respectively. The multifunctional activity of LfU21 in a combined Parkinson’s disease model underscores its therapeutic potential and helps identify a target patient cohort for future clinical trials.

The L. fermentum U-21 strain, known for secreting chaperones into the extracellular milieu, emerges as a promising candidate for the development of novel therapeutics termed disaggregases for Parkinson’s disease. Our study focuses on characterizing the secreted protein encoded by the C0965_000195 locus in the genome of this strain. Through sequence analysis and structural predictions, the protein encoded by C0965_000195 is identified as ClpL, homologs of which are known for their chaperone functions. The chaperone activity of ClpL from L. fermentum U-21 is investigated in vivo by assessing the refolding of luciferases with varying thermostabilities from Aliivibrio fischeri and Photorhabdus luminescens within Escherichia coli cells. The results indicate that the clpL gene from L. fermentum U-21 can compensate for the absence of the clpB gene, enhancing the refolding capacity of thermodenatured proteins in clpB-deficient cells. In vitro experiments demonstrate that both spent culture medium containing proteins secreted by L. fermentum U-21 cells, including ClpL, and purified heterologically expressed ClpL partially prevent the thermodenaturation of luciferases. The findings suggest that the ClpL protein from L. fermentum U-21, exhibiting disaggregase properties against aggregating proteins, may represent a key component contributing to the pharmabiotic attributes of this strain.

Strain L. fermentum U-21 secretes chaperones into the medium and it is considered as the candidate for the development of drugs, so-called disaggregases, for Parkinson’s disease therapy. This study is devoted to characterization of secreted protein encoded by C0965_000195 locus. Analysis of sequence and predicted structure of the protein encoded by C0965_000195 allows us to attribute it to the ClpL, homologs of which are known to be chaperones. The chaperone activity of ClpL L. fermentum U-21 was evaluated in vivo by refolding of differing in thermostability luciferases from Aliivibrio fischeri and Photorhabdus luminescens in Escherichia coli cells. It was observed that clpL from L. fermentum U-21 can compensate for the deficiency in the clpB gene and enhance the ability to refold thermodenatured proteins in clpB- cells. In vitro experiments have demonstrated the ability of a spent culture medium containing proteins secreted by L. fermentum U-21 cells, including ClpL, to prevent thermodenaturation of luciferases partially.We suggest that the ClpL protein from L. fermentum U-21 strain, which exhibits disaggregase properties against aggregating proteins, may be one of the clue components that play a role in the pharmabiotic properties of this strain.

Previously, in the strain Streptomyces rimosusATCC10970 (producer of oxytetracycline), the aminoglycoside phosphotransferase AphVIII, determining kanamycin, neomycin, and paromomycin...

Bifidobacteria, a genus of obligate anaerobes, comprise a major component of the intestinal microbiota. Importantly, bifidobacteria participate in immune reactions. These bacteria carry a species-specific operon in which the fn3 gene encodes a multifunctional protein FN3 that mediates bacterial adhesion to the intestinal epithelium and is capable of binding individual cytokines. Bioinformatics and biochemical approaches were used to study the possible interaction of recombinant ∆FN3 fragments of B. longum and B. bifidum strains with cytokines TNF-α, IL-6, IL-8, and IL-10. De novo molecular modeling generated, for the first time, the structural models of species-derived ∆FN3 proteins and revealed new tentative regions for differential cytokine binding. Combined treatment with ∆FN3 and TNF-α induced TNF-α mRNA abundance in the human monocytic cell line. Altogether, these findings provide structural evidence for the regulation of immune reactions by microbiota-derived proteins.