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Small Milk Fat Globules Stimulate Growth of Good Bacteria

    A petri dish to represent researchers looking at the size of milk fat globules.

    Written by: Brittany T. Truong, Ph.D. | Issue # 125 | 2025

    • Milk fat globules are highly complex structures varying in size. They consist of a triglyceride core and three layers of phospholipids and proteins. 
    • A new study found that the structure of milk fat globules, rather than the chemical composition, is critical for modulating interactions with beneficial and pathogenic bacteria found in milk. 
    • Small milk fat globules promote the growth of Bacillus subtilis and Lactobacillus plantarum, or commensal bacteria, while large milk fat globules stimulate biofilm formation, signifying stress.

    Milk is an emulsion of water, protein, and fat globules. The fat globules have been extensively studied in recent years because of their bioactive function. These complex spherical structures act as a source of energy and nutrients, help shape the gut microbiome, and support our immune systems.

    The globules vary widely in structure and size, ranging from 0.1 to 15 μM [1]. The core is made of triglycerides enclosed in a three-layered membrane consisting of phospholipids and proteins. The size of the globule and the presence of its surrounding membrane have been shown to affect digestion [2] and may contribute to infant growth and development [3].

    Studies have also found that they affect interactions between milk and naturally occurring bacteria; however, it was unclear whether this was due to the chemical composition, i.e., the triglycerides and phospholipids, the size of the milk fat globules, or both [1]. 

    In a new study, published in Food Chemistry, researchers at the Hebrew University of Jerusalem found that the size of milk fat globules plays a critical role in modulating interactions between milk and bacteria. Indeed, the size of the globule seems to be more important than the chemical composition. Smaller fat globules are better at promoting the growth of beneficial bacteria compared to larger globules [4]. 

    To determine the effect of structure and composition on bacteria growth, the researchers cultured different strains of bacteria with small or large milk fat globules that had been separated from raw milk or produced in vitro by mammary epithelial cells [4]. 

    The team found that regardless of whether the milk fat globules were isolated from raw milk or produced by the cell model, good bacteria, namely Bacillus subtilis and Lactobacillus plantarum, preferred small milk fat globules compared to large globules. Small globules promoted bacterial growth, while large globules triggered biofilm formation, a protective mechanism that usually signifies stress. Interestingly, the harmful bacteria, i.e., S. aureus and E. coli, did not have a preference [4]. These results indicate that the structure and size of the globule are more important than the chemical composition. 

    The researchers further supported these data with metabolomics. They incubated B. subtilis with small and large fat globules isolated from the mammary epithelial cells and isolated the metabolites. There was a significantly greater number of metabolites produced after treatment with the small fat globules. For example, metabolites associated with the citric acid cycle were elevated. The data suggest that small fat globules support more metabolic activity [4].

    The differences in bacteria growth, biofilm formation, and metabolites can be attributed to the milk fat’s surrounding membrane. Small milk fat globules have a relatively greater surface area of membrane and can provide more nutrients and energy, specifically to the commensal bacteria. There may be protective mechanisms in place that provide a competitive advantage over pathogenic bacteria.   

    This study provides greater insight into the interactions between milk fat and bacteria, which can have important implications for our understanding of milk nutrition and food safety.

    References

    1. Raz C, Paramonov MM, Shemesh M, Argov-Argaman N. The milk fat globule size governs a physiological switch for biofilm formation by bacillus subtilis. Frontiers in Nutrition. 2022 2022-August-11;9.
    2. Garcia C, Antona C, Robert B, Lopez C, Armand M. The size and interfacial composition of milk fat globules are key factors controlling triglycerides bioavailability in simulated human gastro-duodenal digestion. Food Hydrocolloids. 2014 2014/03/01/;35:494-504.
    3. Schipper L, Bartke N, Marintcheva-Petrova M, Schoen S, Vandenplas Y, Hokken-Koelega ACS. Infant formula containing large, milk phospholipid-coated lipid droplets and dairy lipids affects cognitive performance at school age. Front Nutr. 2023;10:1–11.
    4. Raz C, Tzirkel-Hancock N, Shemesh M, Argov-Argaman N. The role of structure in the interaction between bacteria, mammary epithelial cells and milk fat globules from raw or “cultured” milk. Food Chem. 2025 Mar 1;467:142244.