Production of Bioactive Peptides by Lactobacillus Species: From Gene to Application

To compensate for their amino acid auxotrophy, lactobacilli have developed the ability to hydrolyze proteins present in their environment. This proteolytic activity not only generates the free amino acids needed by the bacteria, but also a large variety of peptides, some of which are endowed with biological activities. These so-called “bioactive peptides” (BAPs) are interesting from a nutrition and healthcare perspective. The use of lactic acid bacteria (LAB) such as lactobacilli is an effective strategy for production and valorization of new BAPs. The proteolytic activity of lactobacilli is exerted in a strain- and species-dependent manner: each species exhibits different proteinase content, leading to a large variety of proteolytic activities. This underlines the high potential of Lactobacillus strains to produce novel hydrolysates and BAPs of major interest. This review aims at discussing the potential of different Lactobacillus species to release BAPs from fermentation media and processes. Strategies used for peptide production are presented. Additionally, we propose a methodology to select the most promising Lactobacillus strains as sources of BAPs. This methodology combines conventional approaches and in silico analyses

One-year longitudinal evaluation of sensori-motor functions in APP751SL transgenic mice.

International audienceIntracerebral amyloid-beta (Abeta) peptide deposition is considered to play a key role in Alzheimer's disease and is designated as a principal therapeutic target. The relationship between brain Abeta levels and clinical deficits remains, however, unclear, both in human patients and in animal models of the disease. The purpose of the present study was to investigate, in a transgenic mouse model of brain amyloidosis, the consequences of Abeta deposition on basic neurological functions using a longitudinal approach. Animals were phenotyped at different ages corresponding to graded neuropathological stages (from no extracellular Abeta deposition to high amyloid loads). Sensory functions were evaluated by assessing visual and olfactory abilities and did not show any effects of the amyloid precursor protein (APP) transgene. Motor functions were assessed using multiple experimental paradigms. Results showed that motor strength was considerably reduced in APP transgenic mice compared with control animals. No deficit was noted in a motor coordination test although APP transgenic mice displayed decreased locomotion on a stationary beam. Hypolocomotion was also observed in the standard open-field test. Measures of anxiety obtained in the elevated plus-maze show some evidence of hyperanxiety in 15-month-old transgenic mice. Some of the neurological impairments showed by APP mice had an early onset and worsened with progressive aging, in parallel to gradual accumulation of Abeta in brain parenchyma. Relationships between neuropathologically assessed amyloid loads and behavioral deficits were further explored, and it was observed that motor strength deficits were correlated with cortical amyloid burden

Peptides from fish and crustacean by-products hydrolysates stimulate cholecystokinin release in STC-1 cells

International audienceFish protein hydrolysates (FPH) are of significant interest, due to their potential application as a source of bioactive peptides in nutraceutical and pharmaceutical domains. Here, we investigated the action of FPH from blue whiting (Micromesistius poutassou) and brown shrimp (Penaeus aztecus) on cholecystokinin release from intestinal endocrine cells (STC-1). We demonstrated for the first time that FPH were able to highly stimulate CCK-releasing activity from STC-1 cells and that this stimulation was mainly due to peptide molecules. The partial purification of CCK-stimulating peptides showed that their apparent molecular weight ranged between 1000 and 1500 Da for fish and crustacean FPH, respectively. Finally, in an aim to industrially produce hydrolysates enriched in CCK-stimulating molecules, we tested the effects of membrane processes (ultrafiltration and nanofiltration) on active peptide enrichment

Protein digestion-derived peptides and the peripheral regulation of food intake

The gut plays a central role in energy homeostasis. Food intake regulation strongly relies on the gut-brain axis, and numerous studies have pointed out the significant role played by gut hormones released from enteroendocrine cells. It is well known that digestive products of dietary protein possess a high satiating effect compared to carbohydrates and fat. Nevertheless, the processes occurring in the gut during protein digestion involved in the short-term regulation of food intake are still not totally unraveled. This review provides a concise overview of the current data concerning the implication of food-derived peptides in the peripheral regulation of food intake with a focus on the gut hormones cholecystokinin and glucagon-like peptide 1 regulation and the relationship with some aspects of glucose homeostasis

In silico and experimental data claiming safety aspects and beneficial attributes of the bacteriocinogenic strain enterococcus faecalis B3A-B3B

International audienceThis study aimed at comparing the genome of Enterococcus faecalis B3A-B3B, a bacteriocinogenic strain recently isolated from a healthy Iraqi infant to those of Enterococci of clinical and beneficial grades. The putative genes gelE, cpd, efaAfm, ccf, agg, and cob coding for virulence factors were detected in B3A-B3B strain, which meanwhile resulted to be non-cytotoxic, non-hemolytic, devoid of inflammatory effects, and sensitive to most of the antibiotics tested except for clindamycin and trimethoprim, which resistance is usually ascribed to intrinsic nature. B3A-B3B strain was remarkable for its hydrophobicity, auto-aggregation, adhesion to human Caco-2 cells, and survival in simulated gastrointestinal conditions, and cholesterol assimilation fulfilling therefore key beneficial attributes

Melanosis in <em>Penaeus monodon</em>: involvement of the laccase-like activity of hemocyanin

International audienceIn shrimp, the development of postmortem melanosis resulting from phenoloxidase activities leads to important economic losses. Phenoloxidase enzymes include catechol oxidases, laccases, and tyrosinases, but hemocyanin is also capable of phenoloxidase activities. These activities have been explored in Penaeus monodon, using different substrates. Results highlighted that tyrosinase-specific substrates were little oxidized, whereas hydroquinone (laccase-specific substrate) was more highly oxidized than L-DOPA (nonspecific substrate) in the pereopods and pleopods. Global phenoloxidase activity, assayed with L-DOPA, did not appear thermally stable over time and probably resulted from phenoloxidase enzymes. Conversely, the laccase-like activity assayed with hydroquinone was thermally stable over time, reflecting the thermal stability of hemocyanin. Independently of the anatomical compartment, the temperature, or the substrate, the highest activities were assayed in the cuticular compartments. This study demonstrates the complexity of phenoloxidase activities in P. monodon, and the importance of considering all the activities, including laccase-like activities such as that of hemocyanin

Anti-adhesion and Anti-inflammatory Potential of the Leaderless Class IIb Bacteriocin Enterocin DD14

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Bioactivities of hemorphins released from bovine haemoglobin gastrointestinal digestion: Dual effects on intestinal hormones and DPP-IV regulations

International audienceFood-derived hemorphins were studied for their interactions with intestinal cells in relation to food intake regulations. LLW-H4, LW-H4, VV-H4, W-H7 and H7 were identified in the 2 h-intestinal hydrolysate of haemoglobin simulated gastrointestinal digestion and synthesised. These food-derived hemorphins showed secretagogue properties of the anorexigenic hormones cholecystokinin (CCK) and glucagon-like peptide 1 (GLP-1) when in contact with murine STC-1 cells. They did not show significant modulatory effect on the corresponding prohormones mRNA levels. However, they downregulated the enzyme PC1 that processes proglucagon into GLP-1 specifically in the intestine. Moreover, VV-H4, VV-H7 & H7 were potent inhibitors of the GLP-1 inactivating dipeptidyl-peptidase IV (DPP-IV) and transiently upregulated its mRNA in human Caco-2 cells. These results suggest that food-derived hemorphins display dual luminal effects that participate at different levels in food intake and glycaemia regulation and add to the known roles of the special class of food-derived opioid peptides, the hemorphins

In vitro probiotic properties of selected lactobacilli and multi-strain consortium on immune function, gut barrier strengthening and gut hormone secretion

International audienceLactobacillus reuteri ICVB395, L. gasseri ICVB392 and L. gasseri ICVB396 strains, isolated from vaginal microbiota, were investigated for their probiotic traits. L. reuteri ICVB395 strain and the 3RG consortium, associating these three Lactobacillus strains, showed the best anti-inflammatory profile on peripheral blood mononuclear cell (PBMC) while L. gasseri ICVB392 was the most potent together with the 3RG consortium to strengthen a Caco-2-derived epithelial barrier. The three studied strains induced various secretion levels of glucagon-like peptide 1 (GLP-1) and cholecystokinin (CCK) by STC-1 enteroendocrine cells, whereas the 3RG consortium was globally less performing. Specific antagonists of protein G receptors, CaSR (Calcium-Sensing Receptor) and GPRC6A (G protein-coupled receptor family C group 6 member A), and inhibitor of the peptide transporter Pept-1 provoked differential modulation of the GLP-1 and CCK secretion by STC-1 cells, indicating that different mechanisms are involved in the capacity of lactobacilli and the 3RG to modulate gut hormones secretion