Changes in gut microbiota and lactose intolerance symptoms before and after daily lactose supplementation in individuals with the lactase nonpersistent genotype

Lonneke Janssen Duijghuijsen*, Ellen Looijesteijn, Maartje van den Belt, Beatrix Gerhard, Martin Ziegler, Renata Ariens, Reina Tjoelker, Jan Geurts

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: Approximately 70%–100% of the Asian adult population is lactase nonpersistent (LNP). The literature shows that many individuals with
the LNP-genotype can consume 12 g of lactose without experiencing gastrointestinal discomfort. Repetitive consumption of lactose may reduce
intolerance symptoms via adaptation of the gut microbiota.
Objective: This study aimed to assess the effects of daily consumption of incremental lactose doses on microbiota composition and function, and
intolerance symptoms.
Methods: Twenty-five healthy adults of Asian origin, carrying the LNP-genotype were included in this 12-wk before and after intervention trial. Par-
ticipants consumed gradually increasing lactose doses from 3 to 6 g to 12 g twice daily, each daily dose of 6 g, 12 g, or 24 g being provided for 4
consecutive weeks. Participants handed-in repeated stool samples and underwent a 25 g lactose challenge hydrogen breath test (HBT) before and after the
12-wk intervention. Daily gastrointestinal symptoms and total symptom scores (TSSs) during the lactose challenge were recorded.
Results: A significant increase from 5.5% 7.6% to 10.4% 9.6% was observed in Bifidobacterium relative abundance after the intervention (P ¼
0.009), accompanied by a 2-fold increase (570 269 U/g; P < 0.001) in fecal β-galactosidase activity compared with baseline (272 158 U/g). A 1.5-
fold decrease (incremental area under the curve; P ¼ 0.01) in expired hydrogen was observed during the second HBT (38 35 ppm⋅min), compared with
the baseline HBT (57 38 ppm⋅min). There was a nonsignificant decrease in TSS (10.6 8.3 before compared with 8.1 7.2 after intervention; P ¼
0.09). Daily consumption of lactose was well tolerated, with mild to no gastrointestinal complaints reported during the intervention.
Conclusions: Increased levels of Bifidobacterium indicate an adaptation of the gut microbiota upon repetitive consumption of incremental doses of
lactose, which was well tolerated as demonstrated by reduced expired hydrogen concentrations during the second 25-g lactose HBT. Bifidobacteria
metabolize lactose without gas production thereby potentially reducing intestinal gas formation in the gut of individuals with the LNP-genotype. This
increased lactose tolerance possibly lifts the necessity to remove nutrient-rich dairy foods completely from the diet.
The trial is registered at the International Clinical Trials Registry Platform: NL9516. The effect of dietary lactose in lactase nonpersistent individuals on
gut microbiota.
Original languageEnglish
Pages (from-to)702-710
JournalThe American journal of clinical nutrition
Issue number3
Early online date28 Dec 2023
Publication statusPublished - Mar 2024


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