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Whether the gut microbiome in obesity is characterized by lower diversity and altered composition at the phylum or genus level may be more accurately investigated using high-throughput sequencing technologies. We conducted a systematic review in PubMed and Embase including 32 cross-sectional studies assessing the gut microbiome composition by high-throughput sequencing in obese and non-obese adults. A significantly lower alpha diversity (Shannon index) in obese versus non-obese adults was observed in nine out of 22 studies, and meta-analysis of seven studies revealed a non-significant mean difference (−0.06, 95% CI −0.24, 0.12, I2 = 81%). At the phylum level, significantly more Firmicutes and fewer Bacteroidetes in obese versus non-obese adults were observed in six out of seventeen, and in four out of eighteen studies, respectively. Meta-analyses of six studies revealed significantly higher Firmicutes (5.50, 95% 0.27, 10.73, I2 = 81%) and non-significantly lower Bacteroidetes (−4.79, 95% CI −10.77, 1.20, I2 = 86%). At the genus level, lower relative proportions of Bifidobacterium and Eggerthella and higher Acidaminococcus, Anaerococcus, Catenibacterium, Dialister, Dorea, Escherichia-Shigella, Eubacterium, Fusobacterium, Megasphera, Prevotella, Roseburia, Streptococcus, and Sutterella were found in obese versus non-obese adults. Although a proportion of studies found lower diversity and differences in gut microbiome composition in obese versus non-obese adults, the observed heterogeneity across studies precludes clear answers.

ObjectiveSugar-sweetened beverage (SSB) consumption had substantially increased across successive US birth cohorts until 2000, and adolescents and young adults under age 50 years have the highest consumption. However, the link between SSBs and early-onset colorectal cancer (EO-CRC) remains unexamined.DesignIn the Nurses’ Health Study II (1991–2015), we prospectively investigated the association of SSB intake in adulthood and adolescence with EO-CRC risk among 95 464 women who had reported adulthood beverage intake using validated food frequency questionnaires (FFQs) every 4 years. A subset of 41 272 participants reported beverage intake at age 13–18 years using a validated high school-FFQ in 1998. Cox proportional hazards models were used to estimate relative risks (RRs) with 95% CIs.ResultsWe documented 109 EO-CRC cases. Compared with individuals who consumed <1 serving/week of SSBs in adulthood, women who consumed ≥2 servings/day had a more than doubled risk of EO-CRC (RR 2.18; 95% CI 1.10 to 4.35; ptrend=0.02), with a 16% higher risk (RR 1.16; 95% CI 1.00 to 1.36) per serving/day increase. Each serving/day increment of SSB intake at age 13–18 years was associated with a 32% higher risk of EO-CRC (RR 1.32; 95% CI 1.00 to 1.75). Replacing each serving/day of adulthood SSB intake with that of artificially sweetened beverages, coffee, reduced fat milk or total milk was associated with a 17%–36% lower risk of EO-CRC.ConclusionHigher SSB intake in adulthood and adolescence was associated with a higher risk of EO-CRC among women. Reduction of SSB consumption among adolescents and young adults may serve as a potential strategy to alleviate the growing burden of EO-CRC.

Abstract There is an increasing interest in investigating dietary strategies able to modulate the gut microbial ecosystem which, in turn, may play a key role in human health. Dietary fibers (DFs) are widely recognized as molecules with prebiotic effects. The main objective of this systematic review was to: (i) analyze the results available on the impact of DF intervention on short chain fatty acids (SCFAs) production; (ii) evaluate the interplay between the type of DF intervention, the gut microbiota composition and its metabolic activities, and any other health associated outcome evaluated in the host. To this aim, initially, a comprehensive database of literature on human intervention studies assessing the effect of confirmed and candidate prebiotics on the microbial ecosystem was developed. Subsequently, studies performed on DFs and analyzing at least the impact on SCFA levels were extracted from the database. A total of 44 studies from 42 manuscripts were selected for the analysis. Among the different types of fiber, inulin was the DF investigated the most (n = 11). Regarding the results obtained on the ability of fiber to modulate total SCFAs, seven studies reported a significant increase, while no significant changes were reported in five studies, depending on the analytical methodology used. A total of 26 studies did not show significant differences in individual SCFAs, while the others reported significant differences for one or more SCFAs. The effect of DF interventions on the SCFA profile seemed to be strictly dependent on the dose and the type and structure of DFs. Overall, these results underline that, although affecting microbiota composition and derived metabolites, DFs do not produce univocal significant increase in SCFA levels in apparently healthy adults. In this regard, several factors (i.e., related to the study protocols and analytical methods) have been identified that could have affected the results obtained in the studies evaluated. Future studies are needed to better elucidate the relationship between DFs and gut microbiota in terms of SCFA production and impact on health-related markers

Background Insufficient physical activity (PA) and extensive sedentary behavior (SB) in adolescents has been related to adverse outcomes related to physical fitness, body weight as well as social and psychological health indicators. Furthermore, these behaviors tend to track from adolescence to adulthood, thereby affecting adult chronic disease risk. The knowledge of factors associated with PA and SB is needed particularly in adolescents, in order to plan public health strategies aiming at increasing PA and reducing SB. The aim of this Citizen Science project (conducted between February 2020 and June 2021) was to work together with young citizens on a school-based epidemiologic study assessing device-based measured PA and SB in students (grades 8 or higher) to identify associated factors based on both established as well as co-created questionnaires. Methods In 12 school classes from Berlin and Brandenburg, students were as Citizen Scientists involved in the co-creation of class-specific questionnaires by collecting factors that may influence their PA and SB. Students participating in the study wore thigh-worn accelerometers (activPAL) for seven consecutive days and subsequently completed established as well as the newly developed class-specific questionnaires to ascertain potential influencing factors of PA and SB. Multilevel linear regression models were used to identify factors associated with time spent in moderate-to-vigorous physical activity (MVPA) and SB. Results Accelerometry data with at least four recorded days were available for 119 students (783 recorded days). In models adjusted for age, sex and parental socioeconomic status, high traffic safety around the school (14.8 min/day, 95% CI 0.9, 28.7) and higher degree school type (10.7 min/day, 95% CI 1.7; 19.8) were associated with more time spent in MVPA. From the class-specific questionnaires developed based on input from students, the feeling of being exhausted after school and homework was associated with less time spent in MVPA, while internal motivation to be physically active, active hobbies and working out regularly at a gym were associated with more time spent in MVPA. The potential influencing factors under investigation were not associated with sedentary time (except female sex, which was related to lower sedentary time). Conclusions Although our findings warrant confirmation in larger samples, this Citizen Science study points to potential action points that may be targeted in public health interventions aimed at increasing PA to improve health in adolescents.

Background Higher dairy intake during adulthood has been associated with lower colorectal cancer risk. As colorectal carcinogenesis spans several decades, we hypothesised that higher dairy intake during adolescence is associated with lower risk of colorectal adenoma, a colorectal cancer precursor. Methods In 27,196 females from the Nurses’ Health Study 2, aged 25–42 years at recruitment (1989), who had completed a validated high school diet questionnaire in 1998 and undergone at least one lower bowel endoscopy between 1998 and 2011, logistic regression for clustered data was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). Results Colorectal adenomas were diagnosed in 2239 women. Dairy consumption during adolescence was not associated with colorectal adenoma risk (OR highest vs. lowest [≥4 vs. ≤1.42 servings/day] quintile [95% CI] 0.94 [0.80, 1.11]). By anatomical site, higher adolescent dairy intake was associated with lower rectal (0.63 [0.42, 0.95]), but not proximal (1.01 [0.80, 1.28]) or distal (0.97 [0.76, 1.24]) colon adenoma risk. An inverse association was observed with histologically advanced (0.72 [0.51, 1.00]) but not non-advanced (1.07 [0.86, 1.33]) adenoma. Conclusions In this large cohort of younger women, higher adolescent dairy intake was associated with lower rectal and advanced adenoma risk later in life.

Purpose Circulating IGF-1 concentrations have been associated with higher cancer risk, particularly prostate, breast and colorectal cancer. There is evidence from observational and intervention studies that milk and dairy products intake is associated with higher IGF-1 concentrations, but results were not always consistent. The purpose of this study was to examine the relationship between dairy intake and circulating IGF-1 concentrations in participants of the Second Bavarian Food Consumption Survey, thereby providing data for a German population for the first time. Methods In this cross-sectional study of 526 men and women aged 18–80 years, in contrast to most previous investigations, dietary intake was assessed with a more detailed instrument than food frequency questionnaires (FFQs), i.e., by three 24-h dietary recalls conducted on random days close in time to the blood collection. Circulating IGF-1 concentrations were measured in blood samples. Multivariable linear regression models were used to examine the association of dairy intake with IGF-1 concentrations. Results Each 400 g increment in daily dairy intake was associated with 16.8 µg/L (95% CI 6.9, 26.7) higher IGF-1 concentrations. Each 200 g increment in milk per day was associated with 10.0 µg/L (95% CI 4.2, 15.8) higher IGF-1. In contrast, we observed no association between cheese or yogurt intake and IGF-1 concentrations. Conclusions Our findings are in line with most previous investigations and support the hypothesis that dairy and milk intake are associated with higher IGF-1 concentrations.

Background Despite significant progress in identifying risk factors for colorectal cancer (CRC), factors influencing survival in people with CRC remain less understood. Pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) have been implicated in cancer progression and may influence CRC outcomes. We investigated associations between genetically predicted levels of IL-6 and TNF-α signaling pathways and mortality in people with CRC. Methods We conducted a two-sample Mendelian randomization (MR) analysis using cis-acting single nucleotide polymorphisms (SNPs) associated with soluble IL-6 receptor alpha (sIL6-RA) and IL-6 signal transducer gp130 (IL6ST), representing IL-6 signaling, and with TNF-α, and its soluble receptors (sTNF-R1, sTNF-R2). SNPs were obtained separately from two large genome-wide association studies (GWAS): deCODE and UK Biobank (UKB). The outcome was CRC-specific mortality among 16,964 CRC cases (4010 deaths) in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Analyses were stratified by tumor site and stage. The inverse variance weighted (IVW) method, incorporating a correlation matrix for dependent SNPs, was used for primary analyses. Because literature links TNF-α to CRC incidence, we additionally performed a simulation study to evaluate the potential impact of collider bias resulting from restricting analyses to CRC cases. Results Genetically predicted sIL6-RA was weakly positively associated with CRC-specific mortality (deCODE-SNPs ( n  = 13) HR per 1 SD increase: 1.06; 95% CI: 1.00–1.12; UKB-SNPs ( n  = 11) HR: 1.09; 95% CI: 1.02–1.17). Genetically proxied IL6ST levels showed no association with CRC-specific mortality in the overall sample (deCODE-SNPs ( n  = 19) HR: 1.04; 95% CI: 0.90–1.21; UKB-SNPs ( n  = 9) HR: 1.11; 95% CI: 0.87–2.42), while higher IL6ST levels were associated with increased mortality among patients with stage 2/3 disease (deCODE-SNPs ( n  = 19) HR: 1.45; 95% CI: 1.10–1.91; UKB-SNPs ( n  = 9) HR: 1.87; 95% CI: 1.22–2.89). No associations were observed for TNF-α, sTNF-R1, or sTNF-R2. Findings for all exposures were consistent across both GWAS datasets. Simulation analyses for TNF-α indicated collider bias was present but limited in magnitude. Conclusions Our findings suggest that IL-6 signaling may play a role in CRC progression although of limited magnitude, whereas TNF-related pathways appear less relevant for prognosis.

Purpose Protein-rich foods show heterogeneous associations with the risk of type 2 diabetes (T2D) and it remains unclear whether habitual protein intake is related to T2D risk. We carried out an umbrella review of systematic reviews (SR) of randomised trials and/or cohort studies on protein intake in relation to risks of T2D. Methods Following a pre-specified protocol (PROSPERO: CRD42018082395), we retrieved SRs on protein intake and T2D risk published between July 1st 2009 and May 22nd 2022, and assessed the methodological quality and outcome-specific certainty of the evidence using a modified version of AMSTAR 2 and NutriGrade, respectively. The overall certainty of evidence was rated according to predefined criteria. Results Eight SRs were identified of which six contained meta-analyses. The majority of SRs on total protein intake had moderate or high methodological quality and moderate outcome-specific certainty of evidence according to NutriGrade, however, the latter was low for the majority of SRs on animal and plant protein. Six of the eight SRs reported risk increases with both total and animal protein. According to one SR, total protein intake in studies was ~ 21 energy percentage (%E) in the highest intake category and 15%E in the lowest intake category. Relative Risks comparing high versus low intake in most recent SRs ranged from 1.09 (two SRs, 95% CIs 1.02–1.15 and 1.06–1.13) to 1.11 (1.05–1.16) for total protein (between 8 and 12 cohort studies included) and from 1.13 (1.08–1.19) to 1.19 (two SRs, 1.11–1.28 and 1.11–1.28) (8–9 cohort studies) for animal protein. However, SRs on RCTs examining major glycaemic traits (HbA 1c , fasting glucose, fasting insulin) do not support a clear biological link with T2D risk. For plant protein, some recent SRs pointed towards risk decreases and non-linear associations, however, the majority did not support an association with T2D risk. Conclusion Higher total protein intake was possibly associated with higher T2D risk, while there is insufficient evidence for a risk increase with higher intakes of animal protein and a risk decrease with plant protein intake. Given that most SRs on plant protein did not indicate an association, there is possibly a lack of an effect.

BackgroundEmerging evidence suggests that insulin resistance (IR) may influence coronary artery disease (CAD) progression. However, the relationship between dietary insulinemic potential and IR surrogate markers and CAD severity remains unclear.MethodsThis cross-sectional study utilized data from the Nutrition Heshmat Registry (NUTHER) in Guilan, Iran, including 930 patients at risk for CAD. CAD severity was assessed using the Gensini score based on angiographic findings. Dietary intake was evaluated using a validated 168-item food frequency questionnaire (FFQ), with energy-adjusted dietary insulin load, and dietary insulin index calculated accordingly. The triglyceride-glucose (TyG)-BMI index was derived as a surrogate marker of insulin resistance.ResultsOf the 930 patients analyzed, 565 were categorized as having less severe CAD (Gensini score < 60) and 365 as severe CAD (Gensini score ≥ 60). Multiple regression models adjusted for various confounding factors showed that participants in the highest quartile of the TyG-BMI index had a 1.98-fold higher odds of severe CAD (OR (95%CI) = 1.98 (1.31–2.99); P-for-trend = 0.001), while those in the highest quartile of energy-adjusted dietary insulin load, and dietary insulin index had 2.41-fold and 2.22-fold increased odds of severe CAD, respectively (Q4 ORs (95%CIs) = 2.41 (1.41–4.12) for e.a.IL, and 2.22 (1.29–3.82) for e.a.II; P-for-trend < 0.001).ConclusionOur significant findings suggest that higher TyG-BMI, dietary insulin load, and insulin index are likely associated with an increased odds of severe CAD. Monitoring and modifying dietary insulinemic potential and improving metabolic health may serve as practical strategies for reducing CAD severity in at-risk populations.

The pappalysins pregnancy associated plasma protein-A (PAPP-A) and -A2 (PAPP-A2) act as proteinases of insulin-like growth factor-1 (IGF-1) binding proteins, while stanniocalcin-2 (STC2) was identified as a pappalysin inhibitor. While there is some evidence from studies in children and adolescents, it is unclear whether these molecules are related to concentrations of IGF-1 and its binding proteins in adults. We investigated cross-sectionally the association of circulating PAPP-A, PAPP-A2 and STC2 with IGF-1 and its binding proteins (IGFBPs) in 394 adult pretest participants (20–69 years) of the German National Cohort Berlin North study center. Plasma PAPP-A, PAPP-A2, total and free IGF-1, IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-5 and STC2 were measured by ELISAs. The associations of PAPP-A, PAPP-A2 and STC2 with IGF-1 or IGFBPs were investigated using multivariable linear regression analyses adjusting for age, sex, body mass index and pretest phase. We observed significant inverse associations of PAPP-A2 (difference in concentrations per 0.5 ng/mL higher PAPP-A2 levels) with total IGF-1 (− 4.3 ng/mL; 95% CI − 7.0; − 1.6), the IGF-1:IGFBP-3 molar ratio (− 0.34%; 95%-CI − 0.59; − 0.09), but not free IGF-1 and a positive association with IGFBP-2 (11.9 ng/mL; 95% CI 5.0; 18.8). PAPP-A was not related to total or free IGF-1, but positively associated with IGFBP-5. STC2 was inversely related to total IGF-1, IGFBP-2 and IGFBP-3 and positively to IGFBP-1. This first investigation of these associations in a general adult population supports the hypothesis that PAPP-A2 as well as STC2 play a role for IGF-1 and its binding proteins, especially for total IGF-1. The role of PAPP-A2 and STC2 for health and disease in adults warrants further investigation.