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.

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).

Monocyte eukaryotic initiation factor 2 signaling differentiates 17-hydroxy-docosahexaenoic acid levels and pain.

Our goal was to probe the potential transcriptomic basis for the relationship between plasma levels of the specialized pro-resolving precursor, 17-hydroxy-docosahexaenoic acid (17-HDHA) and chronic pain. Participants with osteoarthritis (average age of 62.3, 60% were female,  = 30) were stratified by levels of 17-HDHA and self-reported pain scores.

Comparative effectiveness of various exercise interventions on central sensitisation indices: A systematic review and network meta-analysis.

Background: Central sensitisation (CS) increases musculoskeletal pain. Quantitative sensory testing (QST) or self-report questionnaires might indicate CS. Indices of CS might be suppressed by exercise, although the optimal exercise regimen remains unclear.

Supplementation with Citrus Low-Methoxy Pectin Reduces Levels of Inflammation and Anxiety in Healthy Volunteers: A Pilot Controlled Dietary Intervention Study.

Although low-methoxy (LM) pectin (polysaccharides extracted from citrus peels) can reduce inflammation by binding to and inhibiting the TLR-2 pathway in animal models and in vitro studies, the anti-inflammatory effects of LM pectin in humans and mood have not been explored to date. The purpose of this study is to assess the role of dietary supplementation with LM pectin in healthy volunteers on inflammatory markers and on mood, specifically anxiety and depression. We carried out a 4-week dietary intervention with LM citrus pectin on healthy volunteers (N = 14, age 40 ± 16 y, BMI 24.

Physical Therapy for Knee Pain Relief Induces Changes in Gut Microbiome Composition: A Secondary Analysis of Data From a Randomized Controlled Trial.

Background: Aerobic exercise alters gut microbiome composition, yet the impact of gentle physiotherapy on gut microbiome and its relation to muscle strengthening and physical function remains unexplored.

Hypothesis: Physiotherapy exercises modulate gut microbiome composition and changes in gut microbes are linked to improvements in muscle strength or function.

Study Design: Secondary data analysis of samples from a randomized controlled trial.

Metagenomic changes in response to antibiotic treatment in severe orthopedic trauma patients.

We investigated changes in microbiome composition and abundance of antimicrobial resistance (AMR) genes post-antibiotic treatment in severe trauma patients. Shotgun sequencing revealed beta diversity (Bray-Curtis) differences between 16 hospitalized multiple rib fractures patients and 10 age- and sex-matched controls ( = 0.043), and between antibiotic-treated and untreated patients ( = 0.

Preoperative inflammatory biomarkers reveal renal involvement in postsurgical mortality in hip fracture patients: an exploratory study.

Background: Hip fractures in frail patients result in excess mortality not accounted for by age or comorbidities. The mechanisms behind the high risk of mortality remain undetermined but are hypothesized to be related to the inflammatory status of frail patients.

Methods: In a prospective observational exploratory cohort study of hospitalized frail hip fracture patients, 92 inflammatory markers were tested in pre-operative serum samples and markers were tested against 6-month survival post-hip fracture surgery and incidence of acute kidney injury (AKI).

Reproducible microbiome composition signatures of anxiety and depressive symptoms.

The gut microbiome is a significant contributor to mental health, with growing evidence linking its composition to anxiety and depressive disorders. Gut microbiome composition is associated with signs of anxiety and depression both in clinically diagnosed mood disorders and subclinically in the general population and may be influenced by dietary fibre intake and the presence of chronic pain. We provide an update of current evidence on the role of gut microbiome composition in depressive and anxiety disorders or symptoms by reviewing available studies.

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%)).

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.

HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19.

SARS-CoV-2 infection results in different outcomes ranging from asymptomatic infection to mild or severe disease and death. Reasons for this diversity of outcome include differences in challenge dose, age, gender, comorbidity and host genomic variation. Human leukocyte antigen (HLA) polymorphisms may influence immune response and disease outcome.

The association of socio-economic and psychological factors with limitations in day-to-day activity over 7 years in newly diagnosed osteoarthritis patients.

Previous research has established links between chronic pain and impaired cognitive ability, as well as between chronic pain and anxiety, in osteoarthritis. Furthermore, there is evidence linking risk of osteoarthritis to lower educational attainment. However, the inter-play of these factors with key social factors (e.

Different genes may be involved in distal and local sensitization: A genome-wide gene-based association study and meta-analysis.

Background: Neuropathic pain symptoms and signs of increased pain sensitization in osteoarthritis (OA) patients may explain persistent pain after total joint replacement (TJR). Therefore, identifying genetic markers associated with pain sensitization and neuropathic-like pain phenotypes could be clinically important in identifying targets for early intervention.

Methods: We performed a genome-wide gene-based association study (GWGAS) using pressure pain detection thresholds (PPTs) from distal pain-free sites (anterior tibia), a measure of distal sensitization, and from proximal pain-affected sites (lateral joint line), a measure of local sensitization, in 320 knee OA participants from the Knee Pain and related health in the Community (KPIC) cohort.

The anti-inflammatory effect of bacterial short chain fatty acids is partially mediated by endocannabinoids.

The endocannabinoid (EC) system has pleiotropic functions in the body. It plays a key role in energy homeostasis and the development of metabolic disorders being a mediator in the relationship between the gut microbiota and host metabolism. In the current study we explore the functional interactions between the endocannabinoid system and the gut microbiome in modulating inflammatory markers.

Chronic social stress induces peripheral and central immune activation, blunted mesolimbic dopamine function, and reduced reward-directed behaviour in mice.

Psychosocial stress is a major risk factor for depression, stress leads to peripheral and central immune activation, immune activation is associated with blunted dopamine (DA) neural function, DA function underlies reward interest, and reduced reward interest is a core symptom of depression. These states might be inter-independent in a complex causal pathway. Whilst animal-model evidence exists for some specific steps in the pathway, there is currently no animal model in which it has been demonstrated that social stress leads to each of these immune, neural and behavioural states.