Lactose: mammary gland synthesis and secretion + digestion in the infant gut
How is lactose synthesised and secreted into breast milk?
The paragraphs in this first section 'How lactose is synthesised and secreted into breast milk' are adapted extracts from Toca et al 2022.
Lactose comprises 80% of carbohydrate found in the milk of placental mammals. Lactose provides 40% of the human infant's caloric intake from breast milk.
Lactocytes synthesize lactose from glucose and galactose within their Golgi apparatus. The lactose and also alpha-lactalbumin are released into Golgi vesicles, and then released through the cell membrane into the lumen by exocytosis.
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Glucose is transported into the lactocyte from the blood flow, through the basolateral membrane of the lactocyte. After a meal, up to 98% of the glucose used to create milk comes from plasma glucose, although this percentage drops considerably (to perhaps 60% if fasting, when other precursors (glycogen, galactose) are also used.)
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Galactose is critical for human metabolism, not just because of its role as source of energy, but because it is required for the production of molecules such as galacocerebrosides, gangliosides, mucoproteins, which make up nerve cell membranes. For this reason, galactose has direct relationship with early neurodevelopment.
Lactose synthesis in the Golgi apparentus of the lactocyte involves the action of the synthase enzyme, which is made up of two factors
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Alpha-lactalbumin, a milk serum protein. During gestation, alpha-lactalbumin remains inactive, but at the time of birth, a dramatic drop in progesterone levels stimulates its activity. Lack of alpha-lactalbumin in Cape fur seals, resulting in lack of lactose, is theorised to explain why the seals' mammary glands don't involute when away from infant seals hunting for three weeks at a time.
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Galactosyltransferase.
Lactose production occurs independently from the consumption of lactose-containing dairy products in diet.
Mechanism 1. Lactose is secreted into milk in free form
After synthesis in the Golgi apparentus, free form lactose is released into the alveolar lumen by exocytosis through the apical membrane of the lactocyte, together with alpha-lactalbumin. Lactose secretion increases intra-alveolar osmotic pressure.
Water is drawn from the capillaries which wrap around the alveolus into the lactocytes then into the alveolar lumen. This is how lactose secretion regulates the volume of milk. As a result, the concentration of lactose in milk strongly correlates with volume of milk output.
"Lactose has more opportunities for hydrogen binding and hydration than the inorganic salts in milk (i.e., Cl, Na), which explains why in most species the lactose concentration of milk is inversely correlated with its osmolality and positively correlated with milk volume." (Sadnovikova et al 2021)
Mechanism 2. Lactose is secreted into milk as a component of milk oligosaccharides
Lactose becomes a structural portion of human milk oligosaccharides (HMO). There are more than 200 human milk oligosaccharides (HMO) and they all contain a lactose core in their molecules. Bidobacterium species release lactose from certain HMO via bacterial lactase.
The enzyme lactase is secreted from endothelial cells in the small intestine
Intestinal lactase activity
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Can be detected in the fetal intestine at 8 weeks of gestation
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Increases significantly between weeks 24 and 40
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Peaks at birth
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Reduces progressively with weaning
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Only persists into adulthood in some adults.
Lactase is synthesised in endothelium at the tip of intestinal villi and its production is vulnerable to intestinal injury. New, immature enterocytes are initially lactase deficient.
What happens when undigested lactose reaches the colon?
In infants, lactose is not typically found in the colon or the stool, since it is hydrolysed and absorbed in the small intestine.
In adults only a small percentage of ingested lactose reaches colon, but if it's not hydrolysed, it ferments in the colon.
The following are the key physiological effects when undigested lactose reaches the colon.
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Undigested lactose in small intestine leads to osmotic trapping of water and the osmotic load in the colon is increased.
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Certain colonic microbes such as the lactic acid bacteria Lactobacillus and Bifidobacterium possess beta-galactosidase activity (i.e. bacterial lactase) which allows them to digest and ultilize lactose. They hydrolyze any lactose that arrives in the colon, into glucose and galactose. Lactose fermentation by these colonic bacteria releases
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Lactate
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Short chain fatty acids (SCFA)
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Gases such as hydrogen, carbon dioxide, and methane (H2, CO2, CH4).
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Recommended resources
Is your baby unsettled or having trouble sleeping because of lactose?
Lactose: your breastmilk and your baby depend upon it
Limitations of the hypothesis that lactose back-defusion from 'hyperlactation' decreases breastmilk production and causes breast inflammation
Two six-week-old breastfed babies with severe functional lactose overload of breastfeeding + what happened next
What is the difference between lactose malabsorption, lactose intolerance, and lactose overload?
Selected references
Forsgard RA. Lactose digestion in humans: intestinal lactase appears to be constitutive whereas the colonic microbiome is adaptable. American Journal of Clinical Nutrition. 2019;110:273-279.
Misselwitz B, Butter M, Verbeke K, Fox MR. Update on lactose malabsorption and intolerance: pathogenesis, diagnosis and clinical management. Gut. 2019;68:2080-2091.
Sadovnikova A, Garcia SC, Hovey RC. A comparative review of the extrinsic and intrinsic factors regulating lactose synthesis. Journal of Mammary Gland Biology and Neoplasia. 2021;26(197-215).
Sadovnikova A, Garcia SC, Hovey RC. Comparative review of the cell biology, biochemistry, and genetics of lactose synthesis. Journal of Mammary Gland Biology and Neoplasia. 2021;26(181-196).
Toca MdC, Fernandez A, Orsi M, Tabacco O, Vinderola G. Lactose intolerance: myths and facts. An update. Archivos Argentinos de Pediatria. 2022;120(1):59-66.
