A Comprehensive Evaluation of the Impact of Bovine Milk Containing Different Beta-Casein Profiles on Gut Health of Ageing Mice

Guantario, Barbara; Giribaldi, Marzia; Devirgiliis, Chiara; Finamore, Alberto; Colombino, Elena; Capucchio, Maria Teresa; Evangelista, Rocchina; Motta, Vincenzo; Zinno, Paola; Cirrincione, Simona; Antoniazzi, Sara; Cavallarin, Laura; Roselli, Marianna

doi:10.3390/nu12072147

Cited by 41 publications

(35 citation statements)

References 51 publications

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“…Decreased urinary excretion of acetate was noted in animals fed A1 β-casein compared to animals who received A2 β-casein milk. A study in mice corroborates our findings and shows that milk containing only A2 β-casein results in higher fecal short-chain fatty acids concentrations compared to milk containing a mixture of A1 and A2 β-casein ( Guantario et al., 2020 ).…”

Section: Discussionsupporting

confidence: 89%

Post-weaning A1/A2 β-casein milk intake modulates depressive-like behavior, brain μ-opioid receptors, and the metabolome of rats

et al. 2021

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Summary The postnatal period is critical for brain and behavioral development and is sensitive to environmental stimuli, such as nutrition. Prevention of weaning from maternal milk was previously shown to cause depressive-like behavior in rats. Additionally, loss of dietary casein was found to act as a developmental trigger for a population of brain opioid receptors. Here, we explore the effect of exposure to milk containing A1 and A2 β-casein beyond weaning. A1 but not A2 β-casein milk significantly increased stress-induced immobility in rats, concomitant with an increased abundance of Clostridium histolyticum bacterial group in the caecum and colon of A1 β-casein fed animals, brain region-specific alterations of μ-opioid and oxytocin receptors, and modifications in urinary biochemical profiles. Moreover, urinary gut microbial metabolites strongly correlated with altered brain metabolites. These findings suggest that consumption of milk containing A1 β-casein beyond weaning age may affect mood via a possible gut-brain axis mechanism.

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Section: Discussionsupporting

confidence: 89%

Post-weaning A1/A2 β-casein milk intake modulates depressive-like behavior, brain μ-opioid receptors, and the metabolome of rats

et al. 2021

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“…Higher milk consumption has been associated with greater microbiota richness and more abundant Faecalibacterium and Fusobacterium but less Bacteroides in humans [ 45 ]. A recent study showed that supplementing the diet of aging mice with bovine milk increased intestinal levels of short-chain fatty acids through modulation of gut microbiota [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Genetically proxied milk consumption and risk of colorectal, bladder, breast, and prostate cancer: a two-sample Mendelian randomization study

Larsson

Mason

Kar

et al. 2020

BMC Med

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Background Observational studies have shown that milk consumption is inversely associated with colorectal, bladder, and breast cancer risk, but positively associated with prostate cancer. However, whether the associations reflect causality remains debatable. We investigated the potential causal associations of milk consumption with the risk of colorectal, bladder, breast, and prostate cancer using a genetic variant near the LCT gene as proxy for milk consumption. Methods We obtained genetic association estimates for cancer from the UK Biobank (n = 367,643 women and men), FinnGen consortium (n = 135,638 women and men), Breast Cancer Association Consortium (n = 228,951 women), and Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (n = 140,254 men). Milk consumption was proxied by a genetic variant (rs4988235 or rs182549) upstream of the gene encoding lactase, which catalyzes the breakdown of lactose. Results Genetically proxied milk consumption was associated with a reduced risk of colorectal cancer. The odds ratio (OR) for each additional milk intake increasing allele was 0.95 (95% confidence interval [CI] 0.91–0.99; P = 0.009). There was no overall association of genetically predicted milk consumption with bladder (OR 0.99; 95% CI 0.94–1.05; P = 0.836), breast (OR 1.01; 95% CI 1.00–1.02; P = 0.113), and prostate cancer (OR 1.01; 95% CI 0.99–1.02; P = 0.389), but a positive association with prostate cancer was observed in the FinnGen consortium (OR 1.07; 95% CI 1.01–1.13; P = 0.026). Conclusions Our findings strengthen the evidence for a protective role of milk consumption on colorectal cancer risk. There was no or limited evidence that milk consumption affects the risk of bladder, breast, and prostate cancer.

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“…A recent Italian study [116] of diets containing milk from A2A2 cows versus milk containing a mix of A1 and A2 beta-casein provided to ageing mice identified consequential differences in microbiota, with A2 milk leading to higher levels of short-chain fatty acids including butyrate. This affected the gut immunological phenotype and favored CD4 + T cell differentiation, resulting in improved gut villi morphology.…”

Section: Links To Microbiotamentioning

confidence: 99%

Casomorphins and Gliadorphins Have Diverse Systemic Effects Spanning Gut, Brain and Internal Organs

Woodford

2021

IJERPH

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Food-derived opioid peptides include digestive products derived from cereal and dairy diets. If these opioid peptides breach the intestinal barrier, typically linked to permeability and constrained biosynthesis of dipeptidyl peptidase-4 (DPP4), they can attach to opioid receptors. The widespread presence of opioid receptors spanning gut, brain, and internal organs is fundamental to the diverse and systemic effects of food-derived opioids, with effects being evidential across many health conditions. However, manifestation delays following low-intensity long-term exposure create major challenges for clinical trials. Accordingly, it has been easiest to demonstrate causal relationships in digestion-based research where some impacts occur rapidly. Within this environment, the role of the microbiome is evidential but challenging to further elucidate, with microbiome effects ranging across gut-condition indicators and modulators, and potentially as systemic causal factors. Elucidation requires a systemic framework that acknowledges that public-health effects of food-derived opioids are complex with varying genetic susceptibility and confounding factors, together with system-wide interactions and feedbacks. The specific role of the microbiome within this puzzle remains a medical frontier. The easiest albeit challenging nutritional strategy to modify risk is reduced intake of foods containing embedded opioids. In future, constituent modification within specific foods to reduce embedded opioids may become feasible.

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A Comprehensive Evaluation of the Impact of Bovine Milk Containing Different Beta-Casein Profiles on Gut Health of Ageing Mice

Cited by 41 publications

References 51 publications

Post-weaning A1/A2 β-casein milk intake modulates depressive-like behavior, brain μ-opioid receptors, and the metabolome of rats

Post-weaning A1/A2 β-casein milk intake modulates depressive-like behavior, brain μ-opioid receptors, and the metabolome of rats

Genetically proxied milk consumption and risk of colorectal, bladder, breast, and prostate cancer: a two-sample Mendelian randomization study

Casomorphins and Gliadorphins Have Diverse Systemic Effects Spanning Gut, Brain and Internal Organs

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