Abstract
We assessed, for the first time, to what extent the composition of the gut microbiome might explain the cross-sectional association of habitual flavonoid and flavonoid-rich food intake with systolic and diastolic blood pressure (BP) in a community-based sample (N=904) from Northern Germany. Gut microbiome composition was sequenced from 16S ribosomal RNA genes. Higher total flavonoid intakes and specifically the polymer subclass were associated with lower systolic BP (SBP; В ТЗ-Т1: —2.9% [95% CI, -5.1 to −0.7], P=0.01 and -3.7% [95% CI, -5.4 to −1.0], P=0.01). In food-based analyses, a higher intake of berries (SBP, В Q4-Q1: —2.9% [95% CI, -5.2 to −0.6], P=0.01; pulse pressure, -5.5% [95% CI, -9.6 to −1.2], P=0.01) and red wine (SBP, ẞ Q4-Q1: -2.6% [95% CI, −4.8 to −0.3], P=0.03; pulse pressure, -6.1% [95% CI, -10.1 to −2.0], P<0.01) were associated with lower SBP and pulse pressure. There were no associations with diastolic BP. In food-based analyses, higher intakes of anthocyanin-rich berries and red wine were associated with higher alpha diversity (ẞ Q4-Q1: 0.03 [95% CI, 0.0–0.1], P=0.04 and 0.1 [95% CI, 0.03–0.1], P<0.01). Higher intakes of berries and apples/pears were associated with a lower abundance of Parabacteroides (ẞ Q4-Q1: -0.2 [95% CI, —0.4 to −0.1], P<0.01, Q=0.07 and -0.3 [95% CI, -0.4 to −0.1], P< 0.01, Q=0.04). Structural equation modeling of these novel data suggests that microbial factors explained 15.2% to the association between flavonoid-rich foods and clinically relevant lower SBP. Further research should focus on interindividual variability in the gut microbiome in mediating the cardiovascular effects of flavonoid-rich foods.
Generated Summary
This research article presents a cross-sectional analysis that explores the relationship between the gut microbiome and the association between flavonoid-rich food intake and blood pressure (BP). The study utilized data from a community-based sample of 904 individuals from Northern Germany. The primary methodology involved sequencing the gut microbiome using 16S ribosomal RNA genes. The researchers investigated the associations of different flavonoid subclasses (flavanones, anthocyanins, etc.) and food sources (berries, red wine, etc.) with systolic and diastolic BP. Further analysis aimed to determine the mediating effect of the gut microbiome on the associations between dietary flavonoid intake, flavonoid-rich foods, and BP. Structural equation modeling was employed to assess the proportion of variance in the association between flavonoid intake and BP explained by the microbiome. Data on participant characteristics, dietary intake, and lifestyle factors were collected through self-administered questionnaires. Statistical analyses included ANCOVA, and Linear Discriminant Analysis Effect Size analysis to detect genus with significantly different abundances between quantiles of flavonoid subclasses and flavonoid-rich foods. The study was approved by the Ethical review board of the Medical Faculty of Kiel University.
Key Findings & Statistics
- Higher total flavonoid intakes were associated with lower systolic BP (SBP; β -2.9% [95% CI, -5.1 to -0.7], P=0.01 and -3.7% [95% CI, -5.4 to -1.0], P=0.01).
- Higher intake of berries was associated with lower SBP (β -2.9% [95% CI, -5.2 to -0.6], P=0.01) and pulse pressure (-5.5% [95% CI, -9.6 to -1.2], P=0.01).
- Red wine intake was associated with lower SBP (β -2.6% [95% CI, -4.8 to -0.3], P=0.03) and pulse pressure (-6.1% [95% CI, -10.1 to -2.0], P<0.01).
- Higher intakes of anthocyanin-rich berries and red wine were associated with higher alpha diversity (β Q4-Q1: 0.03 [95% CI, 0.0–0.1], P=0.04 and 0.1 [95% CI, 0.03–0.1], P<0.01).
- Higher intakes of berries and apples/pears were associated with a lower abundance of Parabacteroides (β Q4-Q1: -0.2 [95% CI, -0.4 to -0.1], P<0.01, Q=0.07 and -0.3 [95% CI, -0.4 to -0.1], P< 0.01, Q=0.04).
- Mean total habitual flavonoid intake was 695 mg/d (SD, 651; median, 514 mg/d; interquartile range, 279-917) in men and 792 mg/d (SD, 630; median, 605 mg/d; interquartile range, 340–1060) in women.
- Higher intakes of total flavonoids, anthocyanins, polymers, and proanthocyanidin component of the polymer class were associated with lower SBP and PP (Table 2).
- Higher intakes of flavan-3-ols were associated with lower SBP.
- Higher intakes of flavonols and flavones were associated with lower PP (Table 2).
- For red wine, intake of 2.8 glasses (250 mL) per week was associated with 3.7 mm Hg lower SBP of which 15.2% could be explained by a combination of alpha diversity and higher relative abundance of unclassified Ruminococcaceae.
Other Important Findings
- The study found that higher intakes of flavonoid-rich foods, including berries, red wine, and apples/pears, were associated with up to 4 mm Hg lower SBP and PP.
- Higher alpha diversity was associated with lower SBP and beta diversity was associated with both SBP and PP.
- The proportion of the association between intake of berries and SBP that could be explained by the gut microbiome was 7.9% for Parabacteroides, 2.8% for beta diversity, 5.0% for alpha diversity.
- A linear combination of these gut microbiome variables (first principal component: 43% of the variance) explained 11.6% of the association between intake of berries and SBP.
- In food-based analyses, focused on the top foods that contributed to intakes of flavonoid subclasses that were associated with lower BP measures, the study also observed lower BP/PP; berries and red wine were associated with significantly lower SBP and PP (Table 3).
- Higher intakes of apples/pears and peppers were also associated with lower PP.
- The study observed no association of intakes of grapes or tea and SBP or PP, and associations between all flavonoid subclasses and flavonoid-rich foods with diastolic blood pressure were nonsignificant.
- Higher intakes of berries (Q4-Q1=0.03 [95% CI, 0.0–0.1], P=0.04) and red wine (Q4-Q1=0.1 [95% CI, 0.03-0.1], P<0.01) were associated with higher microbial alpha diversity (Figure S2).
- Linear Discriminant Analysis Effect Size analysis confirmed enriched abundance of Oscillibacter and Ruminococcus genus in the highest consumers of red wine compared to the lower consumers (Linear Discriminant Analysis>3.5; P3.5; P<0.05, Figure S6) but not apples/pear (Figure S7).
- There was no significant interaction between sex/menopausal status and intake of flavonoid subclasses in the BP models but the association between a higher red wine intake and lower SBP was greater in premenopausal (β=-0.02, P<0.01) and postmenopausal women (β=-0.01, P=0.01) compared with men (β=0.00, P=0.99).
Limitations Noted in the Document
- As with all observational studies, residual or unmeasured confounding can lead to bias, and the researchers are unable to infer causation from these findings.
- Despite detailed adjustment for a range of dietary and lifestyle variables, there is still the possibility of residual or unmeasured confounding from additional unmeasured factors.
- The value of self-reported dietary assessment has been questioned, and measurement errors are inevitable.
- The study observed limited associations of flavonoid subclasses with the gut microbiome.
- Limited associations of flavonoid subclasses with the gut microbiome, and as flavonoid-rich foods, such as apples/pears, berries, and red wine are important sources of other phytochemicals, it could be these constituents that also contribute to explaining the observed associations.
Conclusion
The study highlights the crucial role of the gut microbiome in associations between flavonoid-rich foods and blood pressure. The findings suggest that higher intakes of flavonoid-rich foods, such as berries and red wine, are associated with lower SBP and PP, along with greater microbial diversity and a shift in the gut microbiome composition. Specifically, the study found that the association between intake of flavonoid-rich foods and BP is modulated by relative abundance of Parabacteroides and bacterial diversity. These data suggest protective associations between dietary-achievable intakes of flavonoid-rich foods and clinically relevant improvements in BP that can be partly explained by characteristics of the gut microbiome. The study’s findings provide evidence that the diversity and composition of the gut microbiome responds to flavonoid intake and subsequently impacts cardiometabolic health. The study’s findings provide evidence that the diversity and composition of the gut microbiome responds to flavonoid intake and subsequently impacts cardiometabolic health. The study suggests the need for future trials that stratify participants according to metabotypes to more accurately investigate the relative importance of metabolism and the gut microbiome on moderating the effect of flavonoids on BP. Overall, the results emphasize the significance of the gut microbiome in mediating the cardiovascular benefits of flavonoid-rich foods. This research also highlights the potential for personalized dietary approaches that consider the interindividual variability of flavonoid metabolism to maximize cardiovascular protection.