The Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and ...effectiveness of these vaccines in a UK community setting.
In this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years vs >55 years), sex, health-care worker status (binary variable), obesity (BMI <30 kg/m2vs ≥30 kg/m2), and comorbidities (binary variable, with or without comorbidities).
Between Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13·5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22·0% (6216 of 28 207) after the second dose of BNT162b2, and by 33·7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71·9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68·5% (9025 of 13 179) after the second dose of BNT162b2, and by 58·7% (104 282 of 177 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1·6 times after the first dose of ChAdOx1 nCoV-19 and 2·9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1·4 times after the first dose of ChAdOx1 nCoV-19 and 1·2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49–68) for ChAdOx1 nCoV-19 and 69% (66–72) for BNT162b2 at 21–44 days and 72% (63–79) for BNT162b2 after 45–59 days.
Systemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days.
ZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association.
Acetate is a short-chain fatty acid (SCFA) produced by gut bacteria, which has been implicated in cardio-metabolic health. Here we examine the relationships of circulating acetate levels with gut ...microbiome composition and diversity and with visceral fat in a large population-based cohort.
Microbiome alpha-diversity was positively correlated with circulating acetate levels (Shannon, Beta 95%CI = 0.12 0.06, 0.18,
= 0.002) after adjustment for covariates. Six serum acetate-associated bacterial genera were also identified, including positive correlations with
,
,
, and
and negative correlations were observed with
and
We also identified a correlation between visceral fat and serum acetate levels (Beta 95%CI = -0.07 -0.11, -0.04,
= 2.8 × 10
) and between visceral fat and
(Beta 95%CI = 0.076 0.042, 0.11,
= 1.44 × 10
). Formal mediation analysis revealed that acetate mediates ∼10% of the total effect of
on visceral fat. The taxonomic diversity showed that
and
comprise at least 18 and 9 species, respectively, including novel bacterial species. By predicting the functional capabilities, we found that
spp. present pathways involved in acetate production and metabolism of vitamins B, whereas we identified pathways related to the biosynthesis of trimethylamine (TMA) and CDP-diacylglycerol in
spp.
Our data indicates that gut microbiota composition and diversity may influence circulating acetate levels and that acetate might exert benefits on certain cardio-metabolic disease risk by decreasing visceral fat.
may play an important role in host health by its production of vitamins B and SCFAs, whereas
might have an opposing effect by influencing negatively the circulating levels of acetate and being involved in the biosynthesis of detrimental lipid compounds.
Personalised dietary modulation of the gut microbiota may be key to disease management. Current investigations provide a broad understanding of the impact of diet on the composition and activity of ...the gut microbiota, yet detailed knowledge in applying diet as an actionable tool remains limited. Further to the relative novelty of the field, approaches are yet to be standardised and extremely heterogeneous research outcomes have ensued. This may be related to confounders associated with complexities in capturing an accurate representation of both diet and the gut microbiota. This review discusses the intricacies and current methodologies of diet-microbial relations, the implications and limitations of these investigative approaches, and future considerations that may assist in accelerating applications. New investigations should consider improved collection of dietary data, further characterisation of mechanistic interactions, and an increased focus on -omic technologies such as metabolomics to describe the bacterial and metabolic activity of food degradation, together with its crosstalk with the host. Furthermore, clinical evidence with health outcomes is required before therapeutic dietary strategies for microbial amelioration can be made. The potential to reach detailed understanding of diet-microbiota relations may depend on re-evaluation, progression, and unification of research methodologies, which consider the complexities of these interactions.
Aims/hypothesis
The gut microbiome is hypothesised to be related to insulin resistance and other metabolic variables. However, data from population-based studies are limited. We investigated ...associations between serologic measures of metabolic health and the gut microbiome in the Northern Finland Birth Cohort 1966 (NFBC1966) and the TwinsUK cohort.
Methods
Among 506 individuals from the NFBC1966 with available faecal microbiome (16S rRNA gene sequence) data, we estimated associations between gut microbiome diversity metrics and serologic levels of HOMA for insulin resistance (HOMA-IR), HbA
1c
and C-reactive protein (CRP) using multivariable linear regression models adjusted for sex, smoking status and BMI. Associations between gut microbiome diversity measures and HOMA-IR and CRP were replicated in 1140 adult participants from TwinsUK, with available faecal microbiome (16S rRNA gene sequence) data. For both cohorts, we used general linear models with a quasi-Poisson distribution and Microbiome Regression-based Kernel Association Test (MiRKAT) to estimate associations of metabolic variables with alpha- and beta diversity metrics, respectively, and generalised additive models for location scale and shape (GAMLSS) fitted with the zero-inflated beta distribution to identify taxa associated with the metabolic markers.
Results
In NFBC1966, alpha diversity was lower in individuals with higher HOMA-IR with a mean of 74.4 (95% CI 70.7, 78.3) amplicon sequence variants (ASVs) for the first quartile of HOMA-IR and 66.6 (95% CI 62.9, 70.4) for the fourth quartile of HOMA-IR. Alpha diversity was also lower with higher HbA
1c
(number of ASVs and Shannon’s diversity,
p
< 0.001 and
p
= 0.003, respectively) and higher CRP (number of ASVs,
p
= 0.025), even after adjustment for BMI and other potential confounders. In TwinsUK, alpha diversity measures were also lower among participants with higher measures of HOMA-IR and CRP. When considering beta diversity measures, we found that microbial community profiles were associated with HOMA-IR in NFBC1966 and TwinsUK, using multivariate MiRKAT models, with binomial deviance dissimilarity
p
values of <0.001. In GAMLSS models, the relative abundances of individual genera
Prevotella
and
Blautia
were associated with HOMA-IR in both cohorts.
Conclusions/interpretation
Overall, higher levels of HOMA-IR, CRP and HbA
1c
were associated with lower microbiome diversity in both the NFBC1966 and TwinsUK cohorts, even after adjustment for BMI and other variables. These results from two distinct population-based cohorts provide evidence for an association between metabolic variables and gut microbial diversity. Further experimental and mechanistic insights are now needed to provide understanding of the potential causal mechanisms that may link the gut microbiota with metabolic health.
Graphical abstract
Chronic inflammation, which can be modulated by diet, is linked to high white blood cell counts and correlates with higher cardiometabolic risk and risk of more severe infections, as in the case of ...COVID-19.
Here, we assessed the association between white blood cell profile (lymphocytes, basophils, eosinophils, neutrophils, monocytes and total white blood cells) as markers of chronic inflammation, habitual diet and gut microbiome composition (determined by sequencing of the 16S RNA) in 986 healthy individuals from the PREDICT-1 nutritional intervention study. We then investigated whether the gut microbiome mediates part of the benefits of vegetable intake on lymphocyte counts.
Higher levels of white blood cells, lymphocytes and basophils were all significantly correlated with lower habitual intake of vegetables, with vegetable intake explaining between 3.59 and 6.58% of variation in white blood cells after adjusting for covariates and multiple testing using false discovery rate (q < 0.1). No such association was seen with fruit intake. A mediation analysis found that 20.00% of the effect of vegetable intake on lymphocyte counts was mediated by one bacterial genus, Collinsella, known to increase with the intake of processed foods and previously associated with fatty liver disease. We further correlated white blood cells to other inflammatory markers including IL6 and GlycA, fasting and post-prandial glucose levels and found a significant relationship between inflammation and diet.
A habitual diet high in vegetables, but not fruits, is linked to a lower inflammatory profile for white blood cells, and a fifth of the effect is mediated by the genus Collinsella.
The ClinicalTrials.gov registration identifier is NCT03479866 .
The optimal dietary pattern to improve metabolic function remains elusive. In a 21-day randomized controlled inpatient crossover feeding trial of 20 insulin-resistant obese women, we assessed the ...extent to which two isocaloric dietary interventions-Mediterranean (M) and high protein (HP)-improved metabolic parameters. Obese women were assigned to one of the following dietary sequences: M-HP or HP-M. Cardiometabolic parameters, body weight, glucose monitoring and gut microbiome composition were assessed. Sixteen women completed the study. Compared to the M diet, the HP diet was more effective in (i) reducing insulin resistance (insulin: Beta (95% CI) = -6.98 (-12.30, -1.65) µIU/mL,
= 0.01; HOMA-IR: -1.78 (95% CI: -3.03, -0.52),
= 9 × 10
); and (ii) improving glycemic variability (-3.13 (-4.60, -1.67) mg/dL,
= 4 × 10
), a risk factor for T2D development. We then identified a panel of 10 microbial genera predictive of the difference in glycemic variability between the two diets. These include the genera
and
, previously associated with glucose homeostasis and insulin resistance. Our results suggest that morbidly obese women with insulin resistance can achieve better control of insulin resistance and glycemic variability on a high HP diet compared to an M diet.
ObjectivesDietary supplements may ameliorate SARS-CoV-2 infection, although scientific evidence to support such a role is lacking. We investigated whether users of the COVID-19 Symptom Study app who ...regularly took dietary supplements were less likely to test positive for SARS-CoV-2 infection.DesignApp-based community survey.Setting445 850 subscribers of an app that was launched to enable self-reported information related to SARS-CoV-2 infection for use in the general population in the UK (n=372 720), the USA (n=45 757) and Sweden (n=27 373).Main exposureSelf-reported regular dietary supplement usage (constant use during previous 3 months) in the first waves of the pandemic up to 31 July 2020.Main outcome measuresSARS-CoV-2 infection confirmed by viral RNA reverse transcriptase PCR test or serology test before 31 July 2020.ResultsIn 372 720 UK participants (175 652 supplement users and 197 068 non-users), those taking probiotics, omega-3 fatty acids, multivitamins or vitamin D had a lower risk of SARS-CoV-2 infection by 14% (95% CI (8% to 19%)), 12% (95% CI (8% to 16%)), 13% (95% CI (10% to 16%)) and 9% (95% CI (6% to 12%)), respectively, after adjusting for potential confounders. No effect was observed for those taking vitamin C, zinc or garlic supplements. On stratification by sex, age and body mass index (BMI), the protective associations in individuals taking probiotics, omega-3 fatty acids, multivitamins and vitamin D were observed in females across all ages and BMI groups, but were not seen in men. The same overall pattern of association was observed in both the US and Swedish cohorts.ConclusionIn women, we observed a modest but significant association between use of probiotics, omega-3 fatty acid, multivitamin or vitamin D supplements and lower risk of testing positive for SARS-CoV-2. We found no clear benefits for men nor any effect of vitamin C, garlic or zinc. Randomised controlled trials are required to confirm these observational findings before any therapeutic recommendations can be made.
Postprandial insulinaemia, triglyceridaemia and measures of inflammation are thought to be more closely associated with cardiovascular risk than fasting measures. Although hypertension is associated ...with altered fasting metabolism, it is unknown as to what extent postprandial lipaemic and inflammatory metabolic responses differ between hypertensive and normotensive individuals. Linear models adjusting for age, sex, body mass index (BMI), visceral fat mass (VFM) and multiple testing (false discovery rate), were used to investigate whether hypertensive cases and normotensive controls had different fasting and postprandial (in response to two standardised test meal challenges) lipaemic, glycaemic, insulinaemic, and inflammatory (glycoprotein acetylation (GlycA)) responses in 989 participants from the ZOE PREDICT-1 nutritional intervention study. Compared to normotensive controls, hypertensive individuals had significantly higher fasting and postprandial insulin, triglycerides, and markers of inflammation after adjusting for age, sex, and BMI (effect size: Beta (Standard Error) ranging from 0.17 (0.08),
= 0.04 for peak insulin to 0.29 (0.08),
= 4.4 × 10
for peak GlycA). No difference was seen for postprandial glucose. When further adjusting for VFM effects were attenuated. Causal mediation analysis suggests that 36% of the variance in postprandial insulin response and 33.8% of variance in postprandial triglyceride response were mediated by VFM. Hypertensive individuals have different postprandial insulinaemic and lipaemic responses compared to normotensive controls and this is partially mediated by visceral fat mass. Consequently, reducing VFM should be a key focus of health interventions in hypertension.
The ClinicalTrials.gov registration identifier is NCT03479866.
A dysregulated postprandial metabolic response is a risk factor for chronic diseases, including type 2 diabetes mellitus (T2DM). The plasma protein N-glycome is implicated in both lipid metabolism ...and T2DM risk. Hence, we first investigate the relationship between the N-glycome and postprandial metabolism and then explore the mediatory role of the plasma N-glycome in the relationship between postprandial lipaemia and T2DM.
We included 995 individuals from the ZOE-PREDICT 1 study with plasma N-glycans measured by ultra-performance liquid chromatography at fasting and triglyceride, insulin, and glucose levels measured at fasting and following a mixed-meal challenge. Linear mixed models were used to investigate the associations between plasma protein N-glycosylation and metabolic response (fasting, postprandial (C
), or change from fasting). A mediation analysis was used to further explore the relationship of the N-glycome in the prediabetes (HbA1c = 39-47 mmol/mol (5.7-6.5%))-postprandial lipaemia association.
We identified 36 out of 55 glycans significantly associated with postprandial triglycerides (C
β ranging from -0.28 for low-branched glycans to 0.30 for GP26) after adjusting for covariates and multiple testing (p
< 0.05). N-glycome composition explained 12.6% of the variance in postprandial triglycerides not already explained by traditional risk factors. Twenty-seven glycans were also associated with postprandial glucose and 12 with postprandial insulin. Additionally, 3 of the postprandial triglyceride-associated glycans (GP9, GP11, and GP32) also correlate with prediabetes and partially mediate the relationship between prediabetes and postprandial triglycerides.
This study provides a comprehensive overview of the interconnections between plasma protein N-glycosylation and postprandial responses, demonstrating the incremental predictive benefit of N-glycans. We also suggest a considerable proportion of the effect of prediabetes on postprandial triglycerides is mediated by some plasma N-glycans.
Association studies have identified several biomarkers for blood pressure and hypertension, but a thorough understanding of their mutual dependencies is lacking. By integrating two different ...high-throughput datasets, biochemical and dietary data, we aim to understand the multifactorial contributors of blood pressure (BP).
We included 4,863 participants from TwinsUK with concurrent BP, metabolomics, genomics, biochemical measures, and dietary data. We used 5-fold cross-validation with the machine learning XGBoost algorithm to identify features of importance in context of one another in TwinsUK (80% training, 20% test). The features tested in TwinsUK were then probed using the same algorithm in an independent dataset of 2,807 individuals from the Qatari Biobank (QBB).
Our model explained 39·2% 4·5%, MAE:11·32 mmHg (95%CI, +/- 0·65) of the variance in systolic BP (SBP) in TwinsUK. Of the top 50 features, the most influential non-demographic variables were dihomo-linolenate, cis-4-decenoyl carnitine, lactate, chloride, urate, and creatinine along with dietary intakes of total, trans and saturated fat. We also highlight the incremental value of each included dimension. Furthermore, we replicated our model in the QBB SBP variance explained = 45·2% (13·39%) cohort and 30 of the top 50 features overlapped between cohorts.
We show that an integrated analysis of omics, biochemical and dietary data improves our understanding of their in-between relationships and expands the range of potential biomarkers for blood pressure. Our results point to potentially key biological pathways to be prioritised for mechanistic studies.
Chronic Disease Research Foundation, Medical Research Council, Wellcome Trust, Qatar Foundation.
PDF
