Adrián Hernández-Mendoza

Food‐derived immunomodulatory peptides

Food proteins contain specific amino acid sequences within their structures that may positively impact bodily functions and have multiple immunomodulatory effects. The functional properties of these specific sequences, also referred to as bioactive peptides, are revealed only after the degradation of native proteins during digestion processes. Currently, milk proteins have been the most explored source of bioactive peptides, which presents an interesting opportunity for the dairy industry. However, plant- and animal-derived proteins have also been shown to be important sources of bioactive peptides. This review summarizes the in vitro and in vivo evidence of the role of various food proteins as sources of immunomodulatory peptides and discusses the possible pathways involving these properties.

Randomized double-blind controlled clinical trial of the blood pressure–lowering effect of fermented milk with Lactococcus lactis: A pilot study

The blood pressure-lowering effect of fermented milk with Lactococcus lactis NRRL B-50571 was evaluated in a double-blind randomized controlled clinical trial with prehypertensive subjects. Participants were randomized into 2 groups (n = 18 each group): one group treated with fermented milk with Lactococcus lactis NRRL B-50571 and a control group treated with artificially acidified milk. Results revealed that during daily consumption of fermented milk for 5 wk, systolic [(116.55 ± 12.26 mmHg vs. 124.77 ± 11.04 mmHg) and diastolic blood pressure (80.7 ± 9 vs. 84.5 ± 8.5 mmHg)] from the fermented milk group was lower than the control group. Additionally, triglyceride, total cholesterol, and low-density lipoprotein in blood serum were lower in the fermented milk group than in the control group. Results demonstrated that daily consumption of fermented milk with Lactococcus lactis (NRRL B-50571) had a blood pressure-lowering effect on prehypertensive subjects. Regular consumption of this product may be used as a potential functional food.

Invited review: Bioactive compounds produced during cheese ripening and health effects associated with aged cheese consumption

Traditionally, cheese is manufactured by converting fluid milk to a semisolid mass through the use of a coagulating agent, such as rennet, acid, heat plus acid, or a combination thereof. Cheese can vary widely in its characteristics, including color, aroma, texture, flavor, and firmness, which can generally be attributed to the production technology, source of the milk, moisture content, and length of aging, in addition to the presence of specific molds, yeast, and bacteria. Among the most important bacteria, lactic acid bacteria (LAB) play a critical role during the cheese-making process. In general, LAB contain cell-envelope proteinases that contribute to the proteolysis of cheese proteins, breaking them down into oligopeptides that can be subsequently taken up by cells via specific peptide transport systems or further degraded into shorter peptides and amino acids through the collaborative action of various intracellular peptidases. Such peptides, amino acids, and their derivatives contribute to the development of texture and flavor in the final cheese. In vitro and in vivo assays have demonstrated that specific sequences of released peptides exhibit biological properties including antioxidant, antimicrobial, anti-inflammatory, immunomodulatory, and analgesic/opioid activity, in addition to angiotensin-converting enzyme inhibition and antiproliferative activity. Some LAB also produce functional lipids (e.g., conjugated linoleic acid) with anti-inflammatory and anticarcinogenic activity, synthesize vitamins and antimicrobial peptides (bacteriocins), or release γ-aminobutyric acid, a nonprotein amino acid that participates in physiological functions, such as neurotransmission and hypotension induction, with diuretic effects. This review provides an overview of the main bioactive components present or released during the ripening process of different types of cheese.

Immunomodulation by hydrolysates and peptides derived from milk proteins

Milk protein-derived peptides have shown immunomodulatory properties either singly or in a mixture. However, information on the behaviour of these compounds is scarce, complicating their further study. This review presents current knowledge on immunomodulatory milk protein-derived peptides, including hydrolysates, peptide fractions and single peptides. The evidence shows that hydrolysates derived from both casein and whey proteins show immunomodulatory effects; however, this bioactivity is mainly attributed to peptides derived from caseins. The identification of peptides in hydrolysates, as well as their characterisation and knowledge of the mechanisms behind their bioactivity, is necessary to further exploit their potential health benefits.

Potential Use Of Food Protein-Derived Peptides In The Treatment Of Inflammatory Diseases.

In recent years, major developments in the field of inflammatory pathophysiology have clearly shown that arthritis, diabetes, intestinal bowel diseases, and obesity, which affect many people around the world, are essentially inflammatory in nature. Different anti-inflammatory drugs have been used to treat these conditions. Some people are able to take these drugs without difficulty, yet others experience negative side effects. Hence, the search for new, natural anti-inflammatory alternatives has rapidly increased in recent years. Evidence has shown that food protein-derived peptides may be one alternative for treating inflammatory diseases. Peptides are encrypted in food proteins, can be released under hydrolysis conditions, and do not cause adverse effects. Despite limited information on the mechanism of action of peptides, in vitro and animal model studies have demonstrated their potential anti-inflammatory activity. Several in vitro studies have demonstrated that peptides can inhibit different pathways of inflammation processes such as that of the nuclear factor kappalight- chain of activated B cells (NF-κB). They can also induce the production of nitric oxide synthase (iNOs) and c-Jun N-terminal kinases (JNK) as well as influence PepT1 and CaRS, the transporters of peptides to the gastrointestinal tract that are responsible for the absorption of dietary peptides in the intestine. However, contradictory evidence has been reported in clinical assays. Hence, in this review, we present the latest research on the anti-inflammatory activity of food protein-derived peptides and provide future perspectives on the use of peptides as potential natural sources of therapeutic treatments.

Mechanistic Pathways Underlying the Antihypertensive Effect of Fermented Milk with Lactococcus lactis NRRL B-50571 in Spontaneously Hypertensive Rats

It has been reported that fermented milk (FM) with Lactococcus lactis NRRL B-50571 had an antihypertensive effect in spontaneously hypertensive rats (SHR) and prehypertensive subjects. Therefore, the objective of the present study was to evaluate the possible mechanisms involved (angiotensin converting enzyme inhibition (ACEI), enhancement of nitric oxide production, antioxidant activity and opioid effect), in the antihypertensive effect of FM with SHR. First, twenty one SHR were randomized into three groups to either receive in a single-oral dose of purified water (negative control), FM, or naloxone (opioid receptor antagonist) + FM. In a parallel study, twenty seven SHR were randomized into three groups to either receive ad libitum purified water (negative control), Captopril or FM. After six weeks of treatment ACEI activity, enhancement of nitric oxide production, and antioxidant activity were evaluated in plasma. Results indicated that opioid receptors were not involved in the hypotensive effect of FM. However, ACEI activity (94 U/L), the oxidative stress index (malondialdehyde/catalase + glutathione peroxidase) 0.9, and nitric oxide in plasma (4.4 ± 1.3 U/L), were significantly different from the negative control, and not significantly different from the Captopril group. Thus, these results suggested that these mechanisms are involved in the hypotensive effect of FM.

Artisanal Sonoran cheese (Cocido cheese): an exploration of its production process, chemical composition and microbiological quality

BACKGROUND The objective of this study was to explore and document the production process of artisanal Cocido cheese and to determine its chemical composition and microbiological quality, considering samples from six dairies and four retailers. RESULTS Cocido cheese is a semi-hard (506-555 g kg-1 of moisture), medium fat (178.3-219.1 g kg-1 ), pasta filata-type cheese made from raw whole cows milk. The production process is not standardized and therefore the chemical and microbiological components of the sampled cheeses varied. Indicator microorganisms significantly decreased (P < 0.05) during the processing of Cocido cheese. Salmonella spp. were not found during the production process, and both Listeria monocytogenes and staphylococcal enterotoxin were absent in the final cheeses. CONCLUSION This study provides more information on one of the most popular artisanal cheeses with high cultural value and economic impact in northwestern Mexico. In view of the foregoing, good manufacturing practices need to be implemented for the manufacture of Cocido cheese. Also, it is of utmost importance to make sure that the heat treatment applied for cooking the curd ensures a phosphatase-negative test, otherwise it would be necessary to pasteurize milk. Nevertheless, since Cocido cheese is a non-ripened, high-moisture product, it is a highly perishable product that could present a health risk if not properly handled.

Milk Fermented by Specific Lactobacillus Strains Regulates the Serum Levels of IL-6, TNF-α and IL-10 Cytokines in a LPS-Stimulated Murine Model

Studies report that metabolites, such as peptides, present in fermented milk with specific lactic acid bacteria, may regulate cytokine production and exert an anti-inflammatory effect. Hence, the cytokine regulatory effect of fermented milk by specific Lactobacillus strains was evaluated in a lipopolysaccharide (LPS)-stimulated murine model. From twelve strains, three (J20, J23 and J28) were selected for their high proteolytic and acidifying capacities in milk and used for the in vivo study. Three treatments (fermented milk, FM; pasteurized fermented milk, PFM; and its <10 kDa fractions, PFM10) were administrated daily for four weeks. After treatments, animals were induced to a systemic inflammation with LPS, and blood samples were collected 6 h post-LPS injection for cytokine analyses. Results showed that FM or PFM significantly (p > 0.05) reduced pro-inflammatory cytokine (IL-6 and TNF-α) concentrations and significantly increased anti-inflammatory (IL-10) cytokine concentrations in comparison to the control; also, pro-inflammatory cytokines were reduced for animals treated with PFM10 (p < 0.05). RP-HPLC-MS/MS analysis showed that water-soluble extracts (<10 kDa) from PFM with J28 presented 15 new peptides, which may be the metabolites involved in the cytokine regulatory effect of fermented milk.

Effect of Milk Fermented with Lactobacillus fermentum on the Inflammatory Response in Mice

Currently, the effect of fermented milk on the T-helper 17 response in inflammatory bowel diseases (IBDs) is unknown. The aim of the present study was to evaluate the effect of milks fermented with Lactobacillus fermentum on the Th1/Th17 response in a murine model of mild IBD. Exopolysaccharide (EPS), lactic acid (LA), and total protein (TP) contents and bacterial concentration were determined. Male C57Bl/6 mice intragastrically received either raw (FM) or pasteurized (PFM) fermented milk before and during a dextran sulfate infusion protocol. Blood, spleen, and colon samples were collected at Weeks 6 and 10. IL-6, IL-10, and TNFα were determined in serum, and IL-17, IL-23, and IFNγ were determined in intestinal mucosa and serum. The FM groups did not differ in cell concentration, LA, or TP content (p > 0.05); FM-J28 had the highest EPS content. Spleen weight and colon length did not differ among the FM groups (p > 0.05). In the FM-J20 and PFM-J20 groups, IL-17 and IFNγ decreased, and the IL-10 concentration was enhanced (p < 0.05) at Week 6. IL-6, TNFα, IL-23, and IFNγ did not differ in serum and mucosa (p > 0.05), and IL-17 was lowest in FM-J28 and FM-J20. Therefore, FM appears to potentially play a role in decreasing the Th17 response. However, further studies are needed to elucidate the FM-mediated anti-inflammatory mechanisms in IBD.

Immune response induced by fermented milk with potential probiotic strains isolated from artisanal Cocido cheese

ABSTRACT Fifteen strains of lactic acid bacteria isolated from artisanal Cocido Mexican cheese were evaluated for their probiotic potential and capacity to modulate the immune system. The results revealed that the strains J20, J23, J24, J25, J27, J28, J32 and J37 presented the highest potential probiotic. Some strains showed resistance to antibiotics; however, they did not exhibit haemolytic activity or mucin degradation. The auto-aggregation capacity ranged from 9.54% to 47.80%, and the hydrophobicity was 21.1%, 63.4% and 78.8% for J27, J24 and J37, respectively. The strains showed high survival capacity (>80%) under different storage conditions and the β-galactosidase activity was 241.77–249.25 MU. Furthermore, the administration of fermented milk by specific strains of Lactobacillus enhanced IL-10 levels and upregulated IL-6 and IgA levels in serum samples of rats. Therefore, the evaluated strains may modulate the immune system and may be good candidates for their inclusion in the manufacture of probiotic-fermented milk.