Host genetics may impact the gut microbiome, as supported by twin studies revealing associations between specific alleles in the host and members or functions of the gut microbiome. However, it is unknown whether the gut microbiota could respond to copy-number variation in host genes, which are considered to be a source of genetic variation.

A new study, led by Dr. Ruth Ley from the Max Planck Institute for Developmental Biology at Tübingen (Germany) and Cornell University in Ithaca (New York, USA), has found that the copy-number variation of the human gene that encodes the salivary amylase enzyme is related to oral and fecal microbiomes in healthy adults.

The researchers focused on associations between copy numbers of the host AMY1 gene that encodes the salivary amylase enzyme and human microbiome diversity and function. This selection has its roots in the influence of complex dietary polysaccharides on the activity of the AMY1 gene, which drove natural selection of human populations during the transition from hunter-gathering to agriculture.

In a dataset of genotyped individuals with associated fecal microbiome diversity taxa belonging to the TwinsUK cohort, Poole and colleagues identified 17 operational taxonomic units (OTUs) that allowed for discrimination of individuals with high and low AMY1 copy numbers. Specifically, members of the Ruminococcaceae family were enriched in the fecal microbiome of participants with high AMY1 count numbers.

The authors also explored the effects of AMY1 copy number distribution (low, medium and high) and diet on the oral and fecal microbiomes of 25 normo-weight healthy participants.

Oral microbiome alfa diversity (richness)—but not overall oral microbiome diversity between subjects—differed according to host AMY1 count numbers, being higher in individuals with higher AMY1 count numbers in comparison with those with low AMY1 count numbers. OTUs found in saliva that discriminated the AMY1 high count numbers group from the AMY1 low count numbers group across 12 time points belonged to the genera Prevotella, Porphyromona (previously linked to periodontitis), Haemophilus and Neisseria.

In contrast to oral microbiome findings, host AMY1 count numbers did not affect fecal microbiome alpha and beta diversity. However, specific OTUs belonging to Ruminococcaceae (Ruminococcus and Oscillospira) and Lachnospiraceae (Blautia, Dorea and Roseburia) discriminated individuals with higher AMY1 count numbers from those with low AMY1 count numbers.

The starches that were not degraded by host amylases were therefore available for the gut microbiota, which is consistent with the enriched levels of Ruminococcaceae in individuals with high AMY1 count numbers.

Although a 2-week standardized diet did not affect either AMY1 higher or lower fecal microbiomes, functional differences were found between both groups. The fecal microbiomes of individuals with AMY1 lower count numbers were enriched in glycoside hydrolases and polysaccharide lyases enzymes involved in degrading complex carbohydrates, which, in turn, is thought to compensate for  the lower levels of host amylase.

The association of fecal short-chain fatty acids with salivary amylase activity but not with AMY1 count numbers indicated that the metabolic output of the gut microbiome might be sensitive to daily salivary amylase activity.

Finally, the researchers inoculated germ-free mice with fecal samples from AMY1 high and lower count number donors. These transplants from donors with higher AMY1 count numbers led to greater adiposity when compared with donors with low AMY1 count numbers, which was not related to changes in diet or intestinal inflammation.

As such, this is the first study that supports an association between copy-number variation of specific human genes involved in starch degradation and the oral and gut microbiomes’ diversity and function.


Poole AC, Goodrich JK, Youngblut ND, et al. Human salivary amylase gene copy number impacts oral and gut microbiomes. Cell Host Microbe. 2019; 25(4):553-64. doi: 10.1016/j.chom.2019.03.001.