Human salivary amylase gene copy number impacts oral and gut microbiomes

Abstract

SummaryHost genetic variation influences the composition of the human microbiome. While studies have focused on associations between the microbiome and single nucleotide polymorphisms in genes, their copy number (CN) can also vary. Here, in a study of human subjects including a 2-week standard diet, we relate oral and gut microbiome to CN at the AMY1 locus, which encodes the gene for salivary amylase, active in starch degradation. We show that although diet standardization drove gut microbiome convergence, AMY1 -CN influenced oral and gut microbiome composition and function.The gut microbiomes of low-AMY1 -CN subjects had an enhanced capacity for breakdown of complex carbohydrates. Those of high-AMY1 subjects were enriched in microbiota linked to resistant starch fermentation, had higher fecal SCFAs, and drove higher adiposity when transferred to germfree mice. Gut microbiota results were validated in a larger separate population. This study establishes AMY1 -CN as a genetic factor patterning microbiome composition and function.

Variations in the microbiome due to storage preservatives are not large enough to obscure variations due to factors such as host population, host species, body site, and captivity

“…We observed significant preservative effects on the alpha diversity on only oral and otic samples in vervet monkeys. This is not surprising because microbial communities from each body site are characterized by one or a few signature microbial taxa and preservatives have been shown to affect the presence/absence and abundance of microbial species in the samples (Amato et al, ; Hale et al, ; Poole et al, ; Ochman et al, ; Ott et al, ; Song et al, ; Turnbaugh et al, ; Vlčková et al, ; Yildirim et al, ). The alpha diversity results suggest that relative abundance drives the effect of preservatives rather than simple presence or absence in the oral samples while the phylogeny is needed to see the preservative effect in the otic samples.…”

You are what you eat or you eat what you are?

“…This is supported by studies that have shown that the gut microbiome is heritable, and that the abundance of many microbial taxa is influenced by host genetics [9]. For example, in a recently published study, variation in the copy number of the human salivary amylase gene influenced the gut and oral microbiota [9]. Having differential copy numbers of the human salivary amylase gene influences the expression of the amylase enzyme, and therefore the capacity to degrade starch, which in turn impacts the availability of complex carbohydrates in the gut.…”

“…Indeed the composition of the gut microbiome is affected by multiple factors including the host genetics. This is supported by studies that have shown that the gut microbiome is heritable, and that the abundance of many microbial taxa is influenced by host genetics [9]. For example, in a recently published study, variation in the copy number of the human salivary amylase gene influenced the gut and oral microbiota [9].…”

Functional specialization of human salivary glands and origins of proteins intrinsic to human saliva

“…Saliva also possesses physicochemical properties keeping the oral cavity moist and well lubricated, which are equally provided by saliva proteins, especially mucins (Frenkel and Ribbeck, 2015;Tabak et al, 1982) . Thus, genetic and dosage variation in the saliva proteome will have important biomedical consequences (Helmerhorst and Oppenheim, 2007;Pajic et al, 2019;Poole et al, 2019;Xu et al, 2017) . At the extreme, malfunctioning of the salivary glands due to, for instance, radiation treatment of head and neck cancer, or caused by the relatively common autoimmune disease, Sjögren's syndrome, can lead to major disruptions in protein homeostasis within saliva causing severe complications in oral health that debilitate patient quality of life (Mavragani and Moutsopoulos, 2019;Vissink et al, 2015) .…”