Effect of AMY1 copy number variation and various doses of starch intake on glucose homeostasis: data from a cross-sectional observational study and a crossover meal study

Abstract Background Copy number (CN) variation (CNV) of the salivary amylase gene (AMY1) influences the ability to digest starch and may influence glucose homeostasis, obesity and gut microbiota composition. Hence, the aim was to examine the association of AMY1 CNV with fasting glucose, BMI, and gut microbiota composition considering habitual starch intake and to investigate the effect of AMY1 CNV on the postprandial response after two different starch doses. Methods The Malmö Offspring Study (n = 1764, 18–71 years) was used to assess interaction effects between AMY1 CNV (genotyped by digital droplet polymerase chain reaction) and starch intake (assessed by 4-day food records) on fasting glucose, BMI, and 64 gut bacteria (16S rRNA sequencing). Participants with low (≤ 4 copies, n = 9) and high (≥ 10 copies, n = 10) AMY1 CN were recruited for a crossover meal study to compare postprandial glycemic and insulinemic responses to 40 g and 80 g starch from white wheat bread. Results In the observational study, no overall associations were found between AMY1 CNV and fasting glucose, BMI, or gut microbiota composition. However, interaction effects between AMY1 CNV and habitual starch intake on fasting glucose (P = 0.03) and BMI (P = 0.05) were observed, suggesting inverse associations between AMY1 CNV and fasting glucose and BMI at high starch intake levels and positive association at low starch intake levels. No associations with the gut microbiota were observed. In the meal study, increased postprandial glucose (P = 0.02) and insulin (P = 0.05) were observed in those with high AMY1 CN after consuming 40 g starch. This difference was smaller and nonsignificant after consuming 80 g starch. Conclusions Starch intake modified the observed association between AMY1 CNV and fasting glucose and BMI. Furthermore, depending on the starch dose, a higher postprandial glucose and insulin response was observed in individuals with high AMY1 CN than in those with low AMY1 CN. Trial registration ClinicalTrials.gov, NCT03974126. Registered 4 June 2019—retrospectively registered.

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Salivary amylase gene copy number and its association with fasting and postprandial glucose response

Proceedings of The Nutrition Society ◽

10.1017/s0029665120000853 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Mary Farrell ◽

Emily Sonestedt ◽

Anne Raben ◽

Juscelino Tovar ◽

Stina Ramne ◽

...

Keyword(s):

Observational Study ◽

Copy Number ◽

Fasting Glucose ◽

Postprandial Glucose ◽

Gene Copy ◽

Amylase Gene ◽

Salivary Amylase ◽

Glucose Levels ◽

Copy Numbers ◽

Meal Study

AbstractIntroductionWhen compared to other primates, humans elicit a large variation in the copy number for the salivary amylase gene, AMY1. This variation can range from 2 to 17 copies. The AMY1 gene is responsible for coding for salivary amylase, an enzyme needed to catalyze the hydrolysis of starch molecules into smaller sugars. AMY1 copy number correlates with the amount and activity of salivary amylase. Few studies have investigated the effect of amylase copy number on fasting and postprandial glucose levels. The aim was first to investigate the association between AMY1 copy numbers and fasting glucose in an observational study, and secondly to investigate the difference in postprandial effect of high-starch meals in individuals with either high or low AMY1 copy numbers.Materials and methodsFor the observational study, we used data from 436 participants from the Malmö Offspring Study (MOS) cohort whom have been genotyped for AMY1. For the meal study (conducted during May 2019), we used genotype-based-recall to recruit 24 participants from the observational study of the MOS cohort: 12 with low AMY1 copy number (from the lowest 20%) and 12 with high AMY1 copy numbers (from the highest 20%). Each subject will be served a breakfast meal of white wheat bread on two separate test days: one containing 40 g and the other containing 80 g of carbohydrates (mainly starch). Blood samples will then be taken at various time points to investigate postprandial glucose and insulin responses.ResultsWhen using linear regression analyses adjusting for age and sex, no significant association between AMY1 copy number and fasting glucose was observed (p = 0.23). However, there was a difference (p = 0.05) in fasting glucose levels between the lowest (2–4 copy numbers: 5.31 mmol/L; 95% CI: 5.13–5.50) and highest (10–16 copy numbers: 5.57 mmol/L; 95% CI: 5.39–5.75) copy number groups. The results for the meal study will be obtained in June 2019 and be presented at the conference.DiscussionOur findings of higher fasting glucose among the group with more than 10 AMY1 copy numbers is the first study to find this and needs to be replicated in other populations.

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Microbiome transfer between IL-1RI-/- and wild-type mice during high or low-fat feeding alters metabolic tissue functionality but not glucose homeostasis.

Proceedings of The Nutrition Society ◽

10.1017/s0029665120000403 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Jessica C. Ralston ◽

Kathleen A.J. Mitchelson ◽

Gina M. Lynch ◽

Tam T.T. Tran ◽

Conall R. Strain ◽

...

Keyword(s):

Glucose Tolerance ◽

Gut Microbiota ◽

Glucose Homeostasis ◽

Gut Microbiome ◽

Short Chain Fatty Acids ◽

Microbiota Composition ◽

Wild Type ◽

Low Fat ◽

Unifrac Distance ◽

Gut Microbiota Composition

AbstractReduced inflammatory signaling (IL-1RI-/-) alters metabolic responses to dietary challenges (1). Inflammasome deficiency (e.g. IL-18-/-, Asc-/-) can modify gut microbiota concomitant with hepatosteatosis; an effect that was transferable to wild-type (WT) mice by co-housing (2). Taken together, this evidence suggests that links between diet, microbiota and IL-1RI-signaling can influence metabolic health. Our aim was to determine whether IL-1RI-mediated signaling interacted with the gut microbiome to impact metabolic tissue functionality in a diet-specific fashion. Male WT (C57BL/J6) and IL-1RI-/- mice were fed either high-fat diet (HFD; 45% kcal) or low-fat diet (LFD; 10% kcal) for 24 weeks and were housed i) separately by genotype or ii) with genotypes co-housed together (i.e. isolated vs shared microbial environment; n = 8–10 mice per group). Glucose tolerance and insulin secretion response (1.5 g/kg i.p.), gut microbiota composition and caecal short-chain fatty acids (SCFA) were assessed. Liver and adipose tissue were harvested and examined for triacylglycerol (TAG) formation, cholesterol and metabolic markers (Fasn, Cpt1α, Pparg, Scd1, Dgat1/2), using histology, gas-chromatography and RT-PCR, respectively. Statistical analysis included 1-way or 2-way ANOVA, where appropriate, with Bonferroni post-hoc correction. Co-housing significantly affected gut microbiota composition, illustrated by clustering in PCoA (unweighted UniFrac distance) of co-housed mice but not their single-housed counterparts, on both HFD and LFD. The taxa driving these differences were primarily from Lachnospiraceae and Ruminococcaceae families. Single-housed WT had lower hepatic weight, TAG, cholesterol levels and Fasn despite HFD, an effect lost in their co-housed counterparts, who aligned more to IL-1RI-/- hepatic lipid status. Hepatic Cpt1α was lowest in co-housed WT. Adipose from IL-1RI-/- groups on HFD displayed increased adipocyte size and reduced adipocyte number compared to WT groups, but greater lipogenic potential (Pparg, Scd1, Dgat2) alongside a blunted IL-6 response to pro-inflammatory stimuli (~32%, P = 0.025). Whilst caecal SCFA concentrations were not different between groups, single-housed IL-1RI-/- adipocytes showed greatest sensitivity to SCFA-induced lipogenesis. Interestingly, differences in tissue functionality and gut microbiome occurred despite unaltered glucose tolerance; although there was a trend for phenotypic transfer of body weight via co-housing. For all endpoints examined, similar genotype/co-housing effects were observed for both HFD and LFD with the greatest impacts seen in HFD-fed mice. In conclusion, while the gut microbiome may be an important consideration in dietary interventions, these results question the magnitude of its impact in relation to the IL-1RI-dependent immunometabolism-glucose homeostasis axis.

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Peanut Intake Enriches Butyrate Producing Bacteria and Expression of a Gene Associated With Butyrate Production in Adults With Elevated Fasting Glucose: An RCT

Current Developments in Nutrition ◽

10.1093/cdn/nzab054_033 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 1178-1178

Author(s):

Philip Sapp ◽

Regina Lamendella ◽

Penny Kris-Etherton ◽

Kristina Petersen

Keyword(s):

Gut Microbiota ◽

Fasting Glucose ◽

Gene Annotation ◽

Small Subunit ◽

Functional Gene ◽

Sequence Variant ◽

Microbiota Composition ◽

Fatty Acid Production ◽

Butyrate Production ◽

Gut Microbiota Composition

Abstract Objectives To assess the effect of consuming 28 g/d of peanuts for 6-weeks, compared to an isocaloric lower fat, higher carbohydrate (LFHC) snack, on gut microbiota composition in adults with elevated fasting glucose. Further, to identify functional and compositional differences in responders using metatranscriptomics. Methods In a randomized, crossover trial, 50 adults (52% male; 42 ± 15 y; BMI 28.3 ± 5.6 kg/m2; glucose 100 ± 8 mg/dL) consumed 28g/d of dry roasted, unsalted, peanuts (160 kcal) or a LFHC snack for 6-wk with a 4-wk washout period. Fecal samples were collected at the baseline and endpoint of each period. Gut microbiota composition was measured using 16 rRNA sequencing and QIIME2 for amplicon sequence variant assignment. Metatranscriptomic sequencing was conducted on baseline and endpoint samples from subjects with the greatest reduction in glucose following the peanut condition (n = 24), to measure gene expression related to microbial metabolic pathways. The NUGEN library preparation method was used to generate cDNA. MetaPhlan2 and HUMAnN2 were used for taxonomic and functional gene annotation, and iPATH3 and Pathview were used for mapping to functional gene pathways. Results No between-condition difference in α or β microbiota diversity was observed. Following peanut intake, roseburia and ruminococcaceae were significantly enriched (LDA > 2; P < 0.05). Metatranscriptomics showed enrichment of the K03518 (aerobic carbon-monoxide dehydrogenase small subunit) gene following peanut intake (P < 0.05). Conclusions Enrichment of roseburia was observed following consumption of 28 g/d of peanuts in adults with elevated fasting glucose. Metatranscriptomics revealed enrichment of the K03518 gene, which is associated with short chain fatty acid production and degradation of β-mannans. These results suggest peanut intake enriches a known butyrate producer and the increased expression of a gene implicated in butyrate production adds further support for peanut-induced gut microbiome modulation. Funding Sources The Peanut Institute and the National Center for Advancing Translational Sciences, National Institutes of Health (1UL1TR002014-01).

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