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Objectives Chronic widespread musculoskeletal pain (CWP) is a characteristic symptom of fibromyalgia, which has been shown to be associated with an altered gut microbiome. Microbiome studies to date have not examined the milder CWP phenotype specifically nor have they explored the role of raised BMI. The aim of this study was to investigate whether the microbiome is abnormal in CWP. Methods CWP was assessed using a standardized screening questionnaire in female volunteers from the TwinsUK cohort including 113 CWP cases and 1623 controls. The stool microbiome was characterized using 16S rRNA amplicon sequencing and amplicon sequence variants, and associations with CWP examined using linear mixed-effects models adjusting for BMI, age, diet, family relatedness and technical factors. Results Alpha diversity was significantly lower in CWP cases than controls (Mann–Whitney test, P -values 2.3e-04 and 1.2e-02, for Shannon and Simpson indices respectively). The species Coprococcus comes was significantly depleted in CWP cases (P adj = 3.04e-03). A genome-wide association study (GWAS) performed for C. comes in TwinsUK followed by meta-analysis with three Dutch cohorts (total n  = 3521) resulted in nine suggestive regions, with the most convincing on chromosome 4 near the TRAM1L1 gene (rs76957229, P  = 7.4e-8). A Mendelian randomization study based on the results of the GWAS did not support a causal role for C. comes on the development of CWP. Conclusions We have demonstrated reduced diversity in the microbiome in CWP, indicating an involvement of the gut microbiota in CWP; prospectively the microbiome may offer therapeutic opportunities for this condition. [ABSTRACT FROM AUTHOR]

Socioeconomic inequalities in childhood Body Mass Index (BMI) are becoming increasingly more pronounced across the world. Although countries differ in the direction and strength of these inequalities, cross-national comparative research on this topic is rare. This paper draws on harmonized longitudinal cohort data from four wealthy countries—Germany, the Netherlands, the United Kingdom (UK), and the United States (US)—to 1) map cross-country differences in the magnitude of socioeconomic inequalities in childhood BMI, and 2) to examine cross-country differences in the role of three energy-balance-related behaviors—physical activity, screen time, and breakfast consumption—in explaining these inequalities. Children were aged 5–7 at our first timepoint and were followed up at age 8–11. We used data from the German National Educational Panel Study, the Dutch Generation R study, the UK Millennium Cohort Study and the US Early Childhood Longitudinal-Kindergarten Study. All countries revealed significant inequalities in childhood BMI. The US stood out in having the largest inequalities. Overall, inequalities between children with low versus medium educated parents were smaller than those between children with high versus medium educated parents. The role of energy-balance-related behaviors in explaining inequalities in BMI was surprisingly consistent. Across countries, physical activity did not, while screen time and breakfast consumption did play a role. The only exception was that breakfast consumption did not play a role in the US. Cross-country differences emerged in the relative contribution of each behavior in explaining inequalities in BMI: Breakfast consumption was most important in the UK, screen time explained most in Germany and the US, and breakfast consumption and screen time were equally important in the Netherlands. Our findings suggest that what constitutes the most effective policy intervention differs across countries and that these should target both children from medium as well as low educated families. • All countries showed substantial socioeconomic inequalities in childhood BMI. • In all countries, inequalities in BMI steepen over course of primary school. • Protective factors among the most advantaged seem to mainly drive inequalities. • Across most countries, underlying mechanisms for inequalities in BMI are similar. • The relative contribution of each mechanism to BMI inequalities differs per country. [ABSTRACT FROM AUTHOR]