The gut microbiota plays an important role in cardio-metabolic diseases with diet being among the strongest modulators of gut microbiota composition and function. Resistant dietary carbohydrates are ...fermented to short-chain fatty acids (SCFAs) by the gut bacteria. Fiber and omega-3 rich diets increase SCFAs production and abundance of SCFA-producing bacteria. Likewise, SCFAs can improve gut barrier integrity, glucose, and lipid metabolism, regulate the immune system, the inflammatory response, and blood pressure. Therefore, targeting the gut microbiota with dietary strategies leading to increased SCFA production may benefit cardio-metabolic health. In this review, we provide an overview of the association between diet, SCFAs produced by the gut microbiota and cardio-metabolic diseases. We first discuss the association between the human gut microbiota and cardio-metabolic diseases, then investigate the role of SCFAs and finally explore the beneficial effects of specific dietary interventions that can improve cardio-metabolic outcomes through boosting the SCFA production.
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.
A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who ...reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio = 6.74; 95% confidence interval = 6.31-7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.
The prevalence of osteoarthritis (OA) increases not only because of longer life expectancy but also because of the modern lifestyle, in particular physical inactivity and diets low in fiber and rich ...in sugar and saturated fats, which promote chronic low-grade inflammation and obesity. Adverse alterations of the gut microbiota (GMB) composition, called microbial dysbiosis, may favor metabolic syndrome and inflammaging, two important components of OA onset and evolution. Considering the burden of OA and the need to define preventive and therapeutic interventions targeting the modifiable components of OA, an expert working group was convened by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) to review the potential contribution of GMB to OA. Such a contribution is supported by observational or dietary intervention studies in animal models of OA and in humans. In addition, several well-recognized risk factors of OA interact with GMB. Lastly, GMB is a critical determinant of drug metabolism and bioavailability and may influence the response to OA medications. Further research targeting GMB or its metabolites is needed to move the field of OA from symptomatic management to individualized interventions targeting its pathogenesis.
The human gut microbiome plays a key role in human health
, but 16S characterization lacks quantitative functional annotation
. The fecal metabolome provides a functional readout of microbial ...activity and can be used as an intermediate phenotype mediating host-microbiome interactions
. In this comprehensive description of the fecal metabolome, examining 1,116 metabolites from 786 individuals from a population-based twin study (TwinsUK), the fecal metabolome was found to be only modestly influenced by host genetics (heritability (H
) = 17.9%). One replicated locus at the NAT2 gene was associated with fecal metabolic traits. The fecal metabolome largely reflects gut microbial composition, explaining on average 67.7% (±18.8%) of its variance. It is strongly associated with visceral-fat mass, thereby illustrating potential mechanisms underlying the well-established microbial influence on abdominal obesity. Fecal metabolic profiling thus is a novel tool to explore links among microbiome composition, host phenotypes, and heritable complex traits.
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.
Type 1 diabetes (T1D) is one of the most widely studied complex genetic disorders, and the genes in HLA are reported to account for approximately 40–50% of the familial aggregation of T1D. The major ...genetic determinants of this disease are polymorphisms of class II HLA genes encoding DQ and DR. The DR-DQ haplotypes conferring the highest risk are
DRB1
*03:01-
DQA1
*05:01-
DQB1
*02:01 (abbreviated “DR3”) and
DRB1
*04:01/02/04/05/08-
DQA1
*03:01-
DQB1
*03:02/04 (or
DQB1
*02; abbreviated “DR4”). The risk is much higher for the heterozygote formed by these two haplotypes (OR = 16.59; 95% CI, 13.7–20.1) than for either of the homozygotes (DR3/DR3, OR = 6.32; 95% CI, 5.12–7.80; DR4/DR4, OR = 5.68; 95% CI, 3.91). In addition, some haplotypes confer strong protection from disease, such as
DRB1
*15:01-
DQA1
*01:02-
DQB1
*06:02 (abbreviated “DR2”; OR = 0.03; 95% CI, 0.01–0.07). After adjusting for the genetic correlation with DR and DQ, significant associations can be seen for HLA class II
DPB1
alleles, in particular,
DPB1
*04:02,
DPB1
*03:01, and
DPB1
*02:02. Outside of the class II region, the strongest susceptibility is conferred by class I allele B*39:06 (OR =10.31; 95% CI, 4.21–25.1) and other
HLA-B
alleles. In addition, several loci in the class III region are reported to be associated with T1D, as are some loci telomeric to class I. Not surprisingly, current approaches for the prediction of T1D in screening studies take advantage of genotyping HLA-DR and HLA-DQ loci, which is then combined with family history and screening for autoantibodies directed against islet-cell antigens. Inclusion of additional moderate HLA risk haplotypes may help identify the majority of children with T1D before the onset of the disease.
There is increasing evidence for the role of gut microbial composition in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH) is the most serious form of ...NAFLD where inflammation causes liver damage that can progress to cirrhosis. We have characterized the gut microbiome composition in UK patients with biopsy-proven NASH (n = 65) and compared it to that in healthy controls (n = 76). We report a 7% lower Shannon alpha diversity in NASH patients without cirrhosis (n = 40) compared to controls (p = 2.7x 10
−4
) and a 14% drop in NASH patients with cirrhosis (n = 25, p = 5.0x 10
−4
). Beta diversity (Unweighted UniFrac distance) was also significantly reduced in both NASH (p = 5.6x 10
−25
) and NASH-cirrhosis (p = 8.1x 10
−7
) groups. The genus most strongly associated with NASH in this study was Collinsella (0.29% abundance in controls, 3.45% in NASH without cirrhosis (False Discovery Rate (FDR) p = .008), and 4.38% in NASH with cirrhosis (FDR p = .02)). This genus, which has been linked previously to obesity and atherosclerosis, was also positively correlated with fasting levels of triglycerides (p = .01) and total cholesterol (p = 1.2x 10
−4
) and negatively correlated with high-density lipoprotein cholesterol (p = 2.8x 10
−6
) suggesting that some of the pathways present in this microbial genus may influence lipid metabolism in the host. In patients, we also found decreased abundance of some of the Ruminococcaceae which are known to produce high levels of short-chain fatty acids which can lower inflammation. This may thus contribute to pathology associated with NASH.
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