The gut-liver axis in progressive steatotic liver disease: A focus on bile acid dysregulation.

Introduction: The gut-liver axis regulates metabolic homeostasis, with bile acids (BAs) serving as key signalling molecules. BA dysregulation is implicated in metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction- and alcohol-associated liver disease (MetALD), yet consistent identification of BA markers and their mechanistic roles across different stages of these diseases remain elusive.

Methods: We integrated three complementary studies to examine BA dysregulation: a population-based cohort (1522 females from TwinsUK with serum BA and liver biomarker data), a clinical cohort (30 patients with steatotic liver disease, fibrosis stages F0-F4, and 4 controls), and rodent models (20 rats with MASLD/MetALD vs.

Systematic Review: The Relationship Between the Faecal Microbiome and Colorectal Neoplasia in Shotgun Metagenomic Studies.

Background: The human gut microbiome is of academic and clinical interest. Associations between certain organisms and colorectal neoplasia have been reported, but findings have limited reproducibility in different populations.

Methods: We performed a systematic review of whole metagenome shotgun sequencing studies using faecal samples from patients with colorectal neoplasia and control populations.

Common inflammatory proteins linking frailty and area-level deprivation as key drivers of cardiovascular risk in women.

Background: Chronic inflammation is linked to frailty and deprivation, both of which are comorbid with cardiovascular diseases (CVD). This study aims to identify inflammatory proteins associated with both socioeconomic deprivation and frailty, and assess their role in mediating cardiovascular risk in a large cohort with independent replication.

Methods: We included 2144 TwinsUK females aged 37-84 with concurrent measures of frailty (frailty index), index of multiple deprivation (IMD), cardiovascular risk (ASCVD score), and 74 proteins (Olink inflammation panel).

Multifluid Metabolomics Identifies Novel Biomarkers for Irritable Bowel Syndrome.

: Irritable bowel syndrome (IBS) is a complex disorder affecting 10% of the global population, but the underlying mechanisms remain poorly understood. By integrating multifluid metabolomics, we aimed to identify metabolite markers of IBS in a large population-based cohort. : We included individuals from TwinsUK with and without IBS, ascertained using the Rome III criteria, and analysed serum (232 cases, 1707 controls), urine (185 cases, 1341 controls), and stool (186 cases, 1284 controls) metabolites (Metabolon Inc.

Effects of non-digestible carbohydrates on gut microbiota and microbial metabolites: a randomised, controlled dietary intervention in healthy individuals.

The gut microbiome is impacted by certain types of dietary fibre. However, the type, duration and dose needed to elicit gut microbial changes and whether these changes also influence microbial metabolites remain unclear. This study investigated the effects of supplementing healthy participants with two types of non-digestible carbohydrates (resistant starch (RS) and polydextrose (PD)) on the stool microbiota and microbial metabolite concentrations in plasma, stool and urine, as secondary outcomes in the Dietary Intervention Stem Cells and Colorectal Cancer (DISC) Study.

Vitamin A carotenoids, but not retinoids, mediate the impact of a healthy diet on gut microbial diversity.

Background: Vitamin A is essential for physiological processes like vision and immunity. Vitamin A's effect on gut microbiome composition, which affects absorption and metabolism of other vitamins, is still unknown. Here we examined the relationship between gut metagenome composition and six vitamin A-related metabolites (two retinoid: -retinol, 4 oxoretinoic acid (oxoRA) and four carotenoid metabolites, including beta-cryptoxanthin and three carotene diols).

A Fecal Metabolite Signature of Impaired Fasting Glucose: Results From Two Independent Population-Based Cohorts.

Unlabelled: Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We searched for fecal metabolites, a readout of gut microbiome function, associated with impaired fasting glucose (IFG) in 142 individuals with IFG and 1,105 healthy individuals from the UK Adult Twin Registry (TwinsUK). We used the Cooperative Health Research in the Region of Augsburg (KORA) cohort (318 IFG individuals, 689 healthy individuals) to replicate our findings.

Genetic and gut microbiome determinants of SCFA circulating and fecal levels, postprandial responses and links to chronic and acute inflammation.

Short-chain fatty acids (SCFA) are involved in immune system and inflammatory responses. We comprehensively assessed the host genetic and gut microbial contribution to a panel of eight serum and stool SCFAs in two cohorts (TwinsUK,  = 2507; ZOE PREDICT-1,  = 328), examined their postprandial changes and explored their links with chronic and acute inflammatory responses in healthy individuals and trauma patients. We report low concordance between circulating and fecal SCFAs, significant postprandial changes in most circulating SCFAs, and a heritable genetic component (average : serum = 14%(SD = 14%); stool = 12%(SD = 6%)).

Plasma protein N-glycome composition associates with postprandial lipaemic response.

Background: 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.

The secondary bile acid isoursodeoxycholate correlates with post-prandial lipemia, inflammation, and appetite and changes post-bariatric surgery.

Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool.

Postprandial Responses to a Standardised Meal in Hypertension: The Mediatory Role of Visceral Fat Mass.

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.

Cross-Sectional Blood Metabolite Markers of Hypertension: A Multicohort Analysis of 44,306 Individuals from the COnsortium of METabolomics Studies.

Hypertension is the main modifiable risk factor for cardiovascular morbidity and mortality but discovering molecular mechanisms for targeted treatment has been challenging. Here we investigate associations of blood metabolite markers with hypertension by integrating data from nine intercontinental cohorts from the COnsortium of METabolomics Studies. We included 44,306 individuals with circulating metabolites (up to 813).

Association between dietary niacin and retinal nerve fibre layer thickness in healthy eyes of different ages.

Background: To investigate the relationship between dietary intake of niacin (water-soluble form of vitamin B ) and retinal nerve fibre layer (RNFL) thickness in healthy eyes.

Methods: This cross-sectional study examined the association between daily niacin intake and RNFL thickness in three large population-based cohorts with varied age differences. RNFL thickness was extracted from optical coherence tomography data; energy-adjusted niacin intake was estimated from food frequency questionnaires.

COVID-19 vaccine waning and effectiveness and side-effects of boosters: a prospective community study from the ZOE COVID Study.

Background: With the surge of new SARS-CoV-2 variants, countries have begun offering COVID-19 vaccine booster doses to high-risk groups and, more recently, to the adult population in general. However, uncertainty remains over how long primary vaccination series remain effective, the ideal timing for booster doses, and the safety of heterologous booster regimens. We aimed to investigate COVID-19 primary vaccine series effectiveness and its waning, and the safety and effectiveness of booster doses, in a UK community setting.

Symptom prevalence, duration, and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of omicron and delta variant dominance: a prospective observational study from the ZOE COVID Study.

Background: The SARS-CoV-2 variant of concern, omicron, appears to be less severe than delta. We aim to quantify the differences in symptom prevalence, risk of hospital admission, and symptom duration among the vaccinated population.

Methods: In this prospective longitudinal observational study, we collected data from participants who were self-reporting test results and symptoms in the ZOE COVID app (previously known as the COVID Symptoms Study App).

Characterisation, procedures and heritability of acute dietary intake in the Twins UK cohort: an observational study.

Background: Estimated food records (EFR) are a common dietary assessment method. This investigation aimed to; (1) define the reporting quality of the EFR, (2) characterise acute dietary intake and eating behaviours, (3) describe diet heritability.

Methods: A total of 1974 one-day EFR were collected from 1858 participants in the TwinsUK cohort between 2012 and 2017.

A High Protein Diet Is More Effective in Improving Insulin Resistance and Glycemic Variability Compared to a Mediterranean Diet-A Cross-Over Controlled Inpatient Dietary Study.

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.

Body mass index mediates the effect of the DASH diet on hypertension: Common metabolites underlying the association.

Background: The Dietary Approaches to Stop Hypertension (DASH) diet is beneficial in reducing blood pressure; however, this may be a consequence of concurrent weight reduction. In the present study, we investigated whether body mass index (BMI) mediates the association between the DASH diet and hypertension and investigate common metabolic pathways.

Methods: We included 2424 females from the cross-sectional TwinsUK cohort, with blood pressure, BMI and dietary intake measured within 1.