The researchers began with fresh goat and cow milk obtained from dairy farms, freeze-dried the samples, and reconstituted them to a standardized protein concentration of 1.5 grams per 100 milliliters. They then subjected both milks to a two-step static digestion model designed to mimic the infant gastrointestinal environment. Gastric digestion was simulated at pH 5.3 and 37 degrees Celsius for one hour using pepsin, followed by intestinal digestion at pH 6.6 for two hours with trypsin and bile salts. The reaction was halted by heating, and the resulting digesta were centrifuged to separate the soluble fraction for analysis. It is worth noting, as the authors themselves emphasize, that this static model does not fully reproduce the dynamic conditions of a real infant gut, including gradual acidification, peristalsis, and gastric emptying, so the findings represent a carefully controlled first approximation rather than a clinical verdict.

The first and perhaps most striking result concerned digestibility. When the milks hit the simulated gastric environment, both formed curd particles, but the curds from goat milk were visibly smaller than those from cow milk, a difference that matters because smaller particles present more surface area to digestive enzymes. When the team measured the degree of hydrolysis, a quantitative indicator of how many peptide bonds had been cleaved, goat milk scored significantly higher than cow milk, with a statistical significance of p less than 0.01. This aligns with earlier work showing that goat caseins tend to be digested more efficiently than cow caseins, and with reports that the true ileal protein digestibility of goat milk-based formula reaches 78.3 percent compared with 73.4 percent for cow milk-based formula under simulated infant conditions. The structural basis for this advantage likely lies in the differing casein composition of the two milks and the smaller fat globules in goat milk, which give it a larger specific surface area for lipase contact.

Peptide profiling added a molecular dimension to the story. After simulated digestion, the researchers identified 215 distinct small peptides in goat milk digesta and 206 in cow milk digesta, with only 41 peptides shared between the two. The majority of peptides in both milks fell in the range of 5 to 13 amino acid residues, indicating substantial protein breakdown, but the length distributions differed in telling ways. Functional annotation using the BIOPEP database revealed that the released peptides were most enriched in angiotensin-converting enzyme inhibitors, followed by antioxidant and antibacterial sequences, with cow milk yielding a broader range of functional categories. Notably, both milks released the same immunomodulatory peptide, NPWDQVKR, while cow milk digesta contained several additional immunomodulatory sequences. The allergenicity picture was more nuanced: goat milk produced a greater number of peptides predicted as allergenic by the AllerTOP algorithm, but the abundance of those predicted allergenic peptides was lower than in cow milk. The authors caution that these are computational predictions, not validated immunological measurements, and that larger polypeptides above 3 kilodaltons, including major allergens such as alpha-s1 casein and beta-lactoglobulin, were excluded from the analysis and may retain allergenic epitopes.

To probe the immunological consequences of digestion, the team turned to human colonic organoids, three-dimensional cultures of intestinal epithelial cells that form closed, gut-like cavity structures. The organoids expressed the epithelial markers EPCAM and MUC-2, confirming a successfully differentiated model. When treated with diluted, filter-sterilized digesta from either milk, the organoids responded in a way that distinguished the two sources. Both goat and cow milk digesta significantly upregulated the gene expression of the pro-inflammatory cytokine IL-1beta, but only cow milk digesta triggered a significant rise in IL-6, another pro-inflammatory signal. Neither milk affected the anti-inflammatory cytokine IL-10 or TNF-alpha. The authors are careful to note that inducing pro-inflammatory cytokines is not the same as causing allergy, which requires specific IgE and Th2 responses, but the data do suggest a differential pro-inflammatory potential between the two digested milks. They also acknowledge that the organoids were adult-derived rather than infant-derived, a limitation they hope future work will address with infant intestinal models and protein-level cytokine measurements.

The second half of the study moved downstream to the hindgut, where undigested milk components become fuel for the resident microbiota. Using fecal samples from ten exclusively formula-fed infants aged 4 to 11 months, the researchers set up anaerobic in vitro fermentation systems containing dialyzed digesta from goat or cow milk, with plain medium as a control. One of the most immediately measurable outcomes was gas: supplementation with goat milk digesta significantly reduced total gas production over the 24-hour fermentation period compared with the control, a finding that may resonate with parents familiar with fussiness and bloating in formula-fed babies, though the authors stress that the gap between an in vitro system and clinical symptoms demands further investigation in animals and humans.

Sequencing of the 16S rRNA gene revealed that both milks reshaped the infant fecal microbial community in overlapping but distinguishable ways. The two milks shared 22 of their differentially abundant genera, and both significantly enriched Ligilactobacillus, a genus generally considered beneficial for infant intestinal health, while tending to increase Bifidobacterium. Both milks also significantly reduced the phylum Desulfobacterota, a group that has received little attention in milk-driven microbiome studies but which the authors suggest may be a shared target of microbial regulation. The divergence emerged in the details: goat milk uniquely boosted Lacticaseibacillus, a genus associated with microbial colonization, bacteriocin synthesis, and the promotion of beneficial bacteria, whereas cow milk elevated Salinivibrio and Acinetobacter. Meanwhile, genera linked to colonic inflammation and disease, such as Streptococcus and Colidextribacter, were depressed by one or both interventions. LEfSe analysis identified Ligilactobacillus as the characteristic biomarker for both milk groups.

Untargeted metabolomics of the fermented samples, which identified 1,704 metabolites, showed that both milks profoundly altered the metabolic output of the infant gut community, with 615 differential metabolites in the goat milk comparison and 589 in the cow milk comparison, 512 of them shared. The dominant enriched pathway for both milks was phenylpropanoid biosynthesis, but the secondary pathways diverged sharply. Goat milk digesta shifted metabolism toward tryptophan metabolism, steroid degradation, and cortisol synthesis, while cow milk digesta enriched ABC transporters, neuroactive ligand-receptor interactions, and nicotinate and nicotinamide metabolism. Correlation analysis strengthened these distinctions. In the goat milk system, the metabolites 2-amino-3-carboxymuconic acid semialdehyde and quinolinic acid, both downstream products of the kynurenine pathway of tryptophan catabolism, correlated strongly with Lacticaseibacillus and other goat-specific genera, pointing to enhanced tryptophan catabolism. In the cow milk system, melatonin, L-aspartic acid, p-octopamine, and sinapic acid correlated with the cow-specific genera, and the authors note that gut bacteria can synthesize melatonin from tryptophan and that melatonin supports gut barrier function and microbial homeostasis.

Taken together, the study sketches two distinct functional identities for the two milks. Goat milk digests more completely under simulated infant conditions, generates a lower abundance of predicted allergenic small peptides, reduces fermentation gas, and appears to steer the hindgut community toward enhanced tryptophan catabolism. Cow milk, by contrast, provoked a stronger pro-inflammatory response in colonic organoids but was associated with elevated melatonin and L-aspartic acid, compounds with recognized protective and immunomodulatory roles. The authors are appropriately measured about the implications, emphasizing that the static digestion model, adult-derived organoids, computational allergenicity predictions, and descriptive correlation analyses all impose limits on interpretation. What the study delivers is the most systematic in vitro characterization to date of how goat and cow milk behave, molecule by molecule and microbe by microbe, as they pass through an approximation of the infant digestive system. The next steps, dynamic digestion models, infant-derived intestinal tissue, functional allergy assays, and eventually clinical trials, will determine whether these laboratory distinctions translate into meaningful differences in how babies thrive on the two milks that dominate infant formula production worldwide.

Subject of Research: Comparative simulated gastrointestinal digestion of goat and cow milk in infants, including peptide profiles, immunomodulatory effects, and gut microbiota modulation

Article Title: Goat and cow milk merits distinct nutritional and functional properties based on simulated gastrointestinal digestion of infant

Article References: Chen, J., Zhu, R., Wu, L., Kuang, J., Bian, X., Li, X., Wang, W., Kang, W., Mu, S., Liu, B. Y., Zhao, K., & Li, J. (2026). Goat and cow milk merits distinct nutritional and functional properties based on simulated gastrointestinal digestion of infant. Food Chemistry: X, Article 104582. https://doi.org/10.1016/j.fochx.2026.104582

Image Credits: AI Generated

DOI: Not provided

Keywords: goat milk, cow milk, infant digestion, simulated gastrointestinal digestion, peptidomics, gut microbiota, colonic organoids, bioactive peptides, allergenicity, metabolomics, infant formula, tryptophan metabolism