Effects of sodium nitrite reduction, removal or replacement on cured and cooked meat for microbiological growth, food safety, colon ecosystem, and colorectal carcinogenesis in Fischer 344 rats

Epidemiological and experimental evidence indicated that processed meat consumption is associated with colorectal cancer risks. Several studies suggest the involvement of nitrite or nitrate additives via N-nitroso-compound formation (NOCs). Compared to the reference level (120 mg/kg of ham), sodium nitrite removal and reduction (90 mg/kg) similarly decreased preneoplastic lesions in F344 rats, but only reduction had an inhibitory effect on Listeria monocytogenes growth comparable to that obtained using the reference nitrite level and an effective lipid peroxidation control. Among the three nitrite salt alternatives tested, none of them led to a significant gain when compared to the reference level: vegetable stock, due to nitrate presence, was very similar to this reference nitrite level, yeast extract induced a strong luminal peroxidation and no decrease in preneoplastic lesions in rats despite the absence of NOCs, and polyphenol rich extract induced the clearest downward trend on preneoplastic lesions in rats but the concomitant presence of nitrosyl iron in feces. Except the vegetable stock, other alternatives were less efficient than sodium nitrite in reducing L. monocytogenes growth

Le peptide β-CN(94-123), un peptide bioactif des laits fermentés, comme modulateur de la protection intestinale

Deux populations de cellules épithéliales jouent un rôle crucial dans la défense intestinale : les cellules à mucus qui produisent la mucine MUC2 à l’origine de la formation du gel de mucus et les cellules de Paneth qui libèrent dans la lumière intestinale des molécules à action antimicrobienne ( -défensines, lysozyme, ..). Lors de travaux antérieurs, nous avons montré que la -casomorphine-7 (peptide opioïde issu de la -caséine bovine) est un puissant sécrétagogue du mucus intestinal, suggérant ainsi que des peptides bioactifs du lait pourraient renforcer l’arsenal défensif de l’intestin. Cependant pour être active par voie luminale, la -casomorphine-7 devait être administrée à des concentrations élevées (100 M ou plus). Parallèlement à ces résultats, des données de la littérature dévoilaient la présence de très nombreux peptides bioactifs dans les laits fermentés. Le premier objectif de notre étude était de déterminer si le pool peptidique total (PPT) d’un yaourt pouvait moduler la production de la mucine MUC2 in vitro sur la lignée mucipare intestinale humaine (HT29-MTX). Notre 2ème objectif a ensuite été d'identifier le peptide portant l'activité biologique et d'étudier son impact in vivo sur des facteurs impliqués dans la protection intestinale après administration par voie orale à des rats (une fois par jour durant 9 jours consécutifs). Les résultats obtenus ont montré que le PPT augmente l'expression des mucines MUC2 et MUC4 ainsi que la sécrétion de mucus par les cellules HT29-MTX. Parmi les quatre fractions peptidiques obtenues à partir du PPT par RP-HPLC préparative, seule la fraction C2 était capable de reproduire l'effet in vitro du PPT. La séquence [94-123] de la β-caséine, présente uniquement dans cette fraction C2, régulait également la production de MUC2 et MUC4 dans les cellules HT29-MTX. L’étude menée chez le rat a montré clairement que l'administration orale de ce peptide à des concentrations comparables à celles détectées dans un yaourt (0.01 à 1 M) induit l’expansion des cellules à mucus et de Paneth le long de l'intestin grêle. Ces effets étaient associés à une augmentation de l’expression des mucines MUC2 et MUC4 et de facteurs antibactériens (lysozyme, rdefa5). En conclusion : le peptide -CN(94-123), identifié dans les yaourts, est un nouveau peptide à effet santé ciblant le tractus intestinal. Grâce à son action sur les cellules à mucus et de Paneth, il pourrait maintenir ou restaurer l'homéostasie intestinale et jouer un rôle important dans la protection contre les agents délétères présents dans la lumière

Effects of neurotransmitters, gut hormones, and inflammatory mediators on mucus discharge in rat colon

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A novel bioactive peptide from yoghurts modulates expression of the gel-forming MUC2 mucin as well as population of goblet cells and Paneth cells along the small intestine

Several studies demonstrated that fermented milks may provide a large number of bioactive peptides into the gastrointestinal tract. We previously showed that beta-casomorphin-7, an opioid-like peptide produced from bovine β-casein, strongly stimulates intestinal mucin production in ex vivo and in vitro models, suggesting the potential benefit of milk bioactive peptides on intestinal protection. In the present study, we tested the hypothesis that the total peptide pool (TPP) from a fermented milk (yoghurt) may act on human intestinal mucus-producing cells (HT29-MTX) to induce mucin expression. Our aim was then to identify the peptide(s) carrying the biological activity and to study its impact in vivo on factors involved in gut protection after oral administration to rat pups (once a day, 9 consecutive days). TPP stimulated MUC2 and MUC4 gene expression as well as mucin secretion in HT29-MTX cells. Among the four peptide fractions that were separated by preparative reversed-phase high-performance liquid chromatography, only the C2 fraction was able to mimic the in vitro effect of TPP. Interestingly, the sequence [94-123] of β-casein, present only in C2 fraction, also regulated mucin production in HT29-MTX cells. Oral administration of this peptide to rat pups enhanced the number of goblet cells and Paneth cells along the small intestine. These effects were associated with a higher expression of intestinal mucins (Muc2 and Muc4) and of antibacterial factors (lysozyme, rdefa5). We conclude that the peptide β-CN(94-123) present in yoghurts may maintain or restore intestinal homeostasis and could play an important role in protection against damaging agents of the intestinal lumen

Beta-Casein(94-123)-derived peptides differently modulate production of mucins in intestinal goblet cells

We recently reported the identification of a peptide from yoghurts with promising potential for intestinal health: the sequence (94-123) of bovine β-casein. This peptide, composed of 30 amino acid residues, maintains intestinal homoeostasis through production of the secreted mucin MUC2 and of the transmembrane-associated mucin MUC4. Our study aimed to search for the minimal sequence responsible for the biological activity of β-CN(94-123) by using several strategies based on (i) known bioactive peptides encrypted in β-CN(94-123), (ii) in silico prediction of peptides reactivity and (iii) digestion of β-CN(94-123) by enzymes of intestinal brush border membranes. The revealed sequences were tested in vitro on human intestinal mucus-producing HT29-MTX cells. We demonstrated that β-CN(108-113) (an ACE-inhibitory peptide) and β-CN(114-119) (an opioid peptide named neocasomorphin-6) up-regulated MUC4 expression whereas levels of the secreted mucins MUC2 and MUC5AC remained unchanged. The digestion of β-CN(94-123) by intestinal enzymes showed that the peptides β-CN(94-108) and β-CN(117-123) were present throughout 1·5 to 3 h of digestion, respectively. These two peptides raised MUC5AC expression while β-CN(117-123) also induced a decrease in the level of MUC2 mRNA and protein. In addition, this inhibitory effect was reproduced in airway epithelial cells. In conclusion, β-CN(94-123) is a multifunctional molecule but only the sequence of 30 amino acids has a stimulating effect on the production of MUC2, a crucial factor of intestinal protection

Letter to the Editor: About bovine beta-casofensin genetic variants-A comment on Bruno et al. (2017) Response

International audienc

Protective effects of beta-CN(94-123), a bioactive peptide present in fermented milk, in inflammation and stress-related gastrointestinal disorders

Protective effects of beta-CN(94-123), a bioactive peptide present in fermented milk, in inflammation and stress-related gastrointestinal disorders. Digestive Disease Wee