Distinct Clinical Phenotypes in Lactase Nonpersistence: Symptomatic, Asymptomatic, and Gassy-Asymptomatic

Area of Science:

• Gastroenterology
• Human Genetics
• Microbiome Research

Background:

• Lactase deficiency leads to lactose fermentation in the colon, causing gastrointestinal issues.
• Genetic lactase non-persistence (LNP) doesn't always result in symptoms, indicating other factors are involved.
• Understanding these factors can refine diagnoses and management.

Purpose of the Study:

• To identify distinct subgroups within the lactose non-persistent (LNP) population.
• To investigate the role of the gut microbiome in symptom development in LNP individuals.
• To improve the diagnostic accuracy of lactose intolerance testing.

Main Methods:

• Genotyping for lactase persistence (LP)-associated SNPs in 146 healthy adults.
• Administering a 25g lactose load with measurement of breath hydrogen, methane, blood glucose, and symptoms.
• Profiling gut microbiome composition using 16S-rRNA sequencing in 60 participants.

Main Results:

• Three LNP phenotypes were identified: symptomatic, gassy asymptomatic, and asymptomatic.
• Peak hydrogen production rate showed a stronger correlation with symptom severity than peak hydrogen levels.
• Asymptomatic LNP subgroups exhibited higher abundances of genera like Lactobacillus and Megasphaera.

Conclusions:

• A significant majority (70%) of genetically LNP adults are asymptomatic.
• Classifying LNP individuals into subgroups and using hydrogen production rate can enhance diagnostic precision.
• Microbiome associations require further functional validation in larger studies.