Written by: Lauren Milligan Newmark, Ph.D. | Issue # 116 | 2023
- Genetic variants associated with lactase persistence—the continued production of the enzyme that breaks down the milk sugar lactose into adulthood—may not be the only adaptation humans have to lactose digestion.
- A new study adds to a growing body of research that demonstrates an association between lactose consumption and gut bacteria populations but only among individuals that do not produce lactase.
- Continued lactose consumption in the absence of the lactase enzyme is believed to shift gut bacteria populations toward bacteria that ferment lactose into lactic acid or short-chain fatty acids instead of those that produce gas and other symptoms commonly associated with lactose intolerance.
Being lactose intolerant and being lactase non-persistent (LNP) were once considered two sides of the same coin. If you are LNP, the gene that carries the instructions for making the lactase enzyme is turned off in the cells of your small intestine. Should you indulge in a banana split, the lactose from the ice cream isn’t digested in the small intestine and instead is fermented by bacteria in the colon. Many of the gut bacteria that commonly dine on lactose produce hydrogen, carbon dioxide, and methane as byproducts as they break the milk sugar down into its single sugars’ glucose and galactose. This results in symptoms of gas and bloating that are commonly associated with lactose intolerance and that can be painful and uncomfortable enough for many LNP individuals to avoid lactose altogether.
But these unpleasant symptoms may not be inevitable for people that lack lactase. LNP individuals vary in how they experience lactose digestion. The reasons for this variation are not yet clearly understood; however, likely factors include age, malnutrition, alcohol consumption, and overall health [1-3]. In addition, a growing body of research suggests that the variation could also relate to the individual’s lactose consumption [2-5]. An apple a day keeps the doctor away—could a little lactose a day keep the lactose intolerance away?
It sounds contradictory, but this is precisely what the colonic adaptation hypothesis argues—regular consumption of lactose in LNP individuals is believed to shift the bacterial populations in the colon toward those that metabolize lactose into lactic acid and short-chain fatty acids and away from those that produce hydrogen, carbon dioxide, or methane as byproducts [2-5]. In this way, lactose actually acts as a prebiotic, feeding the population of beneficial bacteria (probiotics) and increasing their numbers. But this hypothesis still requires rigorous testing. Just how frequent the lactose consumption needs to be, how much lactose an individual needs to consume to shift gut microbiota, and which specific types of bacteria are involved in the shift are questions that still need to be addressed.
A new study  from nutritional researchers at the U.S. Department of Agriculture and UC Davis helps to chip away at these pressing questions by studying the interaction between lactose consumption, genetic status for lactase persistence (LP), and gut microbial populations. The study population was an ethnically diverse cohort of 275 healthy adults from Davis, California. All participants had known lactase genotypes for the most common genetic variant associated with LP among individuals of European descent (a single nucleotide polymorphism, or SNP, called rs4988235) . LP individuals express the LCT gene, produce lactase, and can be homozygous dominant (AA genotype) or heterozygous (AG); LNP do not express the LCT gene and are homozygous recessive (GG). Because individuals of African descent could have another genetic variant (conferred by a different SNP) associated with LP, seven LNP study participants (GG genotype) that identified as African American were excluded from analysis. Lactose consumption was calculated from 24-hour recalls from each study participant from two weekdays and one weekend day. To better approximate regular lactose consumption, the researchers also used a food frequency questionnaire (FFQ) to provide data on habitual dairy intake from the previous 12 months. Gut microbiome populations were identified from bacterial DNA analysis on stool samples provided by study participants within 10–14 days from completion of their 24-hour dietary recalls.
This was an observational study, which means the researchers couldn’t control for lactose intake across participants. However, testing their research questions would only be possible if LNP individuals consumed dairy products with lactose. They found that the average daily lactose consumption was higher in LP compared with LNP participants (12.16 vs. 8.72 grams per day), especially if the participants were men . Luckily there were many LNP individuals who consumed comparable amounts of lactose to LP individuals . Sex-specific differences in lactose consumption were found to correlate to differences in dairy intake; men consumed more fluid milk and women consumed more yogurt, which is lower in lactose than milk . This finding highlights why it is so important to measure lactose intake, not just dairy intake; lactose intake in women would have been overestimated if based only on dairy servings.
Consistent with predictions from the colonic adaptation hypothesis, variation in lactose consumption across LNP individuals was associated with differences in gut bacteria populations. LNP participants with a higher daily intake of lactose (>12.46 grams) had larger populations of Lactobacillaceae, a family of lactic acid bacteria that ferment lactose into lactic acid, compared with LNP individuals with low daily intakes of lactose (≤ 5.85 grams) . (For reference, an 8-ounce glass of milk has around 12 grams of lactose).
Gut bacteria were also distinct in a subset of the study population made up of only Caucasian and Hispanic LNP participants . Bacteria from the family Lachnospriaceae were more abundant in high- compared with low-lactose consuming individuals, and the most abundant genera from this family were Blautia, Roseburia, and Coprococcus. This finding is significant because these genera have previously demonstrated the ability to break down lactose into short-chain fatty acids rather than hydrogen, carbon dioxide, and methane, providing additional support for microbial adaptations to lactose consumption across LNP participants .
Importantly, the researchers found no association between lactose intake and gut Lactobacillaceae or Lachnospriaceae populations among LP participants, supporting previous research on lactose consumption and gut microbiomes among LP and LNP individuals. A lactose challenge study on LP and LNP Chinese adults  found a significantly greater amount of short-chain fatty acids were produced by fermentation of lactose in stools from LNP compared with LP subjects. And a study on dairy intake among Dutch adults  found a higher abundance of gut Bifidobacterium was associated with dairy consumption in LNP individuals but not LP individuals. Taken together, these studies strongly suggest that it was not simply high lactose consumption driving the association with gut bacteria but lactose consumption in the absence of lactase.
If you lack lactase and are looking to improve the outcomes from lactose digestion by shifting your gut microbiome, take heed: it is still not known how much lactose you need to consume nor how long you need to keep consuming it to call yourself “adapted” from a microbiome perspective. Data like these are provided by intervention studies, which rely on observational studies (like the Davis study) to generate hypotheses about specific bacteria families (or genera or species) and the quantities of lactose needed to observe an effect. With all the nutritional benefits provided by dairy foods and more than half the world’s population possessing the LNP genotype, such studies are clearly important. Although it might not be possible to change your genes to keep the lactase enzyme turned on, it is encouraging that there may be more than one way to digest lactose without pain and discomfort.
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