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Background and Aims: Emerging evidence suggests a detrimental impact of high red meat intake on hepatic steatosis. We investigated the potential interplay between red meat intake and gut microbiome on circulating levels of trimethylamine N‐oxide (TMAO) and hepatic steatosis risk. Methods: This cross‐sectional study was conducted in a representative sample of 754 community‐dwelling adults in Huoshan, China. Diet was collected using 4 quarterly 3 consecutive 24‐h dietary (12‐day) recalls. We profiled faecal microbiome using 16S ribosomal RNA sequencing and quantified serum TMAO and its precursors using LC‐tandem MS (n = 333). We detected hepatic steatosis by FibroScan. The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated using logistic regression. Results: TMAO levels but not its precursors were positively associated with the likelihood of hepatic steatosis (aOR per 1‐SD increment 1.86, 95% CI 1.04–3.32). We identified 14 bacterial genera whose abundance was associated with TMAO concentration (pFDR <.05) belonging to the phyla Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria families. Per 10 g/day increase in red meat intake was positively associated with TMAO levels among participants who had higher red meat intake (>70 g/day) and higher TMAO‐predicting microbial scores (TMS, β =.045, p =.034), but not among others (pinteraction =.030). TMS significantly modified the positive association between red meat and steatosis (pinteraction =.032), with a stronger association being observed among participants with higher TMS (aOR 1.30, 95% CI 1.07–1.57). Conclusions: The bacterial genera that predicted TMAO levels may jointly modify the association between red meat intake and TMAO levels and the subsequent risk of hepatic steatosis. [ABSTRACT FROM AUTHOR]

Objective: This study assessed the cross‐sectional associations of low‐carbohydrate diets (LCDs) and low‐fat diets (LFDs) with hepatic steatosis in the National Health and Nutrition Examination Survey. Methods: Diet was measured using the 24‐hour recalls. Hepatic steatosis was defined by vibration‐controlled transient elastography. The odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. Substitution analysis was performed using the leave‐one‐out model. Results: Participants with higher adherence scores (comparing extreme tertiles) for an overall (OR = 0.76, 95% CI: 0.61‐0.96, ptrend = 0.049) or a healthful LCD (OR = 0.61, 95% CI: 0.43‐0.87, ptrend < 0.001) exhibited lower odds of steatosis. Replacing 5% of the energy from carbohydrates with total fat and protein (OR = 0.91, 95% CI: 0.83‐0.99) or unsaturated fat and plant protein (OR = 0.89, 95% CI: 0.84‐0.94) was associated with lower steatosis prevalence. High overall (OR = 1.65, 95% CI: 1.13‐2.40, ptrend = 0.006) or unhealthful (OR = 1.41, 95% CI: 1.10‐1.80, ptrend < 0.001) LFD scores were associated with increased likelihood of steatosis. Conclusions: These findings suggest that the associations between LCDs and LFDs and steatosis may depend on the quality and food sources of the macronutrients. [ABSTRACT FROM AUTHOR]

Background and Aims: Hyperinsulinaemia and insulin resistance play a central role in the progression of hepatic steatosis and fibrosis, and diet can modulate insulin response. We thus hypothesised that diet with higher insulinaemic potential is associated with an increased risk of these conditions. Methods: Two empirically dietary indices for hyperinsulinaemia (EDIH) and insulin resistance (EDIR) were derived to identify food groups most predictive of fasting concentrations of C‐peptide and insulin and homeostatic model assessment for insulin resistance respectively. Hepatic steatosis and fibrosis were defined by controlled attenuation parameter and liver stiffness measurement using transient elastography (TE). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. Results: Of the 4171 participants with TE examination, 1436 (age‐standardised prevalence, 33.8%) were diagnosed with steatosis, 255 (5.6%) with advanced fibrosis and 101 (2.2%) with cirrhosis. The multivariable‐adjusted ORs for participants comparing the highest to the lowest EDIH tertile were 1.17 (95% CI: 0.99‐1.39, Ptrend =.005) for steatosis, 1.74 (95% CI: 1.24‐2.44, Ptrend =.001) for advanced fibrosis and 2.05 (95% CI: 1.21‐3.46, Ptrend =.004) for cirrhosis. Similar associations were observed for EDIR with ORs of 1.32 (95% CI: 1.11‐1.55, Ptrend <.001) for steatosis and 1.43 (95% CI: 1.03‐1.99, Ptrend =.006) for advance fibrosis. These positive associations remained among never drinkers and individuals who were free of hepatitis B and/or C. Conclusions: Our findings suggest that hyperinsulinaemia and insulin resistance may partially underlie the influence of diet on hepatic steatosis and fibrosis, and highlight the importance of reducing or avoiding insulinaemic dietary pattern. [ABSTRACT FROM AUTHOR]

Abnormal bowel movements have been related to a variety of hepatocellular carcinoma (HCC) risk factors such as dyslipidemia, diabetes and altered metabolism of bile acids and gut microbiota. However, little is known about whether bowel movement frequency affects the risk of developing HCC. We followed 88 123 women in the Nurses' Health Study (NHS) and 28 824 men in the Health Professionals Follow‐up Study (HPFS) for up to 24 years. The Cox proportional hazards regression model was used to calculate multivariable hazard ratios (HRs) and confidence intervals (95%CI). We documented 101 incident HCC cases. Compared to those with daily bowel movements, participants with bowel movement more than once per day had a multivariable HR of 1.93 (95%CI: 1.18 to 3.16) in the pooled cohorts. For the same comparison, the positive association appeared stronger for men (2.72, 95% CI: 1.14 to 6.44) than for women (1.63, 95% CI: 0.87 to 3.06) but there was no statistically significant heterogeneity by sex (P‐value =.31). We found null associations between bowel movement every 2 days or less and the risk of HCC (HR = 1.05, 95%CI: 0.62 to 1.79). The HR (95%CI) for participants who used laxatives regularly relative to those who never used laxatives was 1.00 (0.64 to 1.55). Our results suggest participants with bowel movement more than once daily is associated with a higher risk of developing HCC compared to those with daily bowel movements. These findings need to be confirmed and potential mechanisms underlying this association need to be elucidated. What's new? Bowel movement frequency has been suggested to play a role in cancer development. However, limited epidemiology studies have yielded mixed results, further complicated by the widespread use of laxative. Using data from two large prospective U.S. cohort studies, here the authors show for the first time that bowel movement more than once daily is associated with a higher risk of developing hepatocellular carcinoma. No association was observed between laxative use and hepatocellular carcinoma risk. The results suggest that intestinal functioning may influence hepatocellular carcinoma development, and future studies are warranted in more diverse racial/ethnic populations and to elucidate potential mechanisms. [ABSTRACT FROM AUTHOR]

Although previous studies have suggested a potential role of sex hormones in the etiology of colorectal cancer (CRC), no study has yet examined the associations between circulating sex hormones and survival among CRC patients. We prospectively assessed the associations of prediagnostic plasma concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone and sex hormone‐binding globulin (SHBG) with CRC‐specific and overall mortality among 609 CRC patients (370 men and 239 postmenopausal women not taking hormone therapy at blood collection) from four U.S. cohorts. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression. We identified 174 deaths (83 CRC‐specific deaths) in men and 106 deaths (70 CRC‐specific deaths) in women. In men, higher circulating level of free testosterone was associated with lower risk of overall (the highest vs. lowest tertiles, HR = 0.66, 95% CI, 0.45–0.99, ptrend = 0.04) and possibly CRC‐specific mortality (HR = 0.73, 95% CI, 0.41–1.29, ptrend = 0.27). We generally observed nonsignificant inverse associations for other sex steroids, and a positive association for SHBG with CRC‐specific mortality among male patients. In women, however, we found a suggestive positive association of estrone with overall (HR = 1.54, 95% CI, 0.92–2.60, ptrend = 0.11) and CRC‐specific mortality (HR = 1.96, 95% CI, 1.01–3.84, ptrend = 0.06). Total estradiol, free estradiol and free testosterone were generally suggestively associated with higher risk of mortality among female patients, although not statistically significant. These findings implicated a potential role of endogenous sex hormones in CRC prognosis, which warrant further investigation. What's new? Premenopausal women with colorectal cancer have a higher 5‐year survival rate than men of the same age, suggesting that female hormones may boost survival. In this prospective study, the authors compared the levels of various sex hormones to mortality rates among 609 CRC patients. In men, they found a beneficial relationship between higher levels of circulating testosterone and lower mortality. In women, though it was not statistically significant, they found a suggestive positive association between higher levels of circulating estrogens and mortality. This is the first study to investigate prediagnostic sex hormone levels as they correlate with CRC mortality. [ABSTRACT FROM AUTHOR]

Although increasing dairy product intake has been associated with risk of several cancers, epidemiological studies on hepatocellular carcinoma are sparse and have yielded inconsistent results. We prospectively assessed the associations of dairy products (total, milk, butter, cheese and yogurt) and their major components (calcium, vitamin D, fats and protein) with the risk of hepatocellular carcinoma development among 51,418 men and 93,427 women in the Health Professionals Follow‐Up Study and the Nurses' Health Study. Diets were collected at baseline and updated every 4 years using validated food frequency questionnaires. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression model. During up to 32 years of follow‐up, a total of 164 hepatocellular carcinoma cases were documented. After adjustment for most known hepatocellular carcinoma risk factors, higher total dairy product intake was associated with an increased risk of hepatocellular carcinoma (highest vs. lowest tertile, HR = 1.85, 95% CI: 1.19–2.88; ptrend = 0.009). For the same comparison, we observed significant positive associations of high‐fat dairy (HR = 1.81, 95% CI: 1.19–2.76; ptrend = 0.008) and butter (HR = 1.58, 95% CI: 1.06–2.36; ptrend = 0.04) with hepatocellular carcinoma risk. There was a nonsignificant inverse association between yogurt intake and hepatocellular carcinoma risk (HR = 0.72, 95% CI: 0.49–1.05; ptrend = 0.26). Our data suggest that higher intake of high‐fat dairy foods was associated with higher, whereas higher yogurt consumption might be associated with lower risk of developing hepatocellular carcinoma among U.S. men and women. What's new? In the US, liver cancer incidence has increased considerably in the last 30 years. Meanwhile, Americans are also eating more dairy products. These authors investigated the association between dairy consumption and risk of hepatocellular carcinoma (HCC). From participants in the Nurses' Health Study and the Health Professionals Follow‐Up Study, they collected diet information at baseline and again every 4 years. Although they considered individual components of dairy food, including calcium, fat, protein, and vitamin D, they found no association between HCC risk and any individual nutrient. They did find higher total dairy intake associated with higher risk of HCC, particularly for high‐fat products. Higher yogurt intake appears to be associated with a suggestive lower risk, which deserves further investigations. [ABSTRACT FROM AUTHOR]

Although experimental evidence suggests calcium-sensing receptor (CASR) as a tumor-suppressor, the prognostic role of tumor CASR expression in colorectal carcinoma remains unclear. We hypothesized that higher tumor CASR expression might be associated with improved survival among colorectal cancer patients. We evaluated tumor expression levels of CASR by immunohistochemistry in 809 incident colorectal cancer patients within the Nurses' Health Study and the Health Professionals Follow-up Study. We used Cox proportional hazards regression models to estimate multivariable hazard ratio (HR) for the association of tumor CASR expression with colorectal cancer-specific and all-cause mortality. We adjusted for potential confounders including tumor biomarkers such as microsatellite instability, CpG island methylator phenotype, LINE-1 methylation level, expressions of PTGS2, VDR and CTNNB1 and mutations of KRAS, BRAF and PIK3CA. There were 240 colorectal cancer-specific deaths and 427 all-cause deaths. The median follow-up of censored patients was 10.8 years (interquartile range: 7.2, 15.1). Compared with patients with no or weak expression of CASR, the multivariable HRs for colorectal cancer-specific mortality were 0.80 [95% confidence interval (CI): 0.55-1.16] in patients with moderate CASR expression and 0.50 (95% CI: 0.32-0.79) in patients with intense CASR expression ( p-trend = 0.003). The corresponding HRs for overall mortality were 0.85 (0.64-1.13) and 0.81 (0.58-1.12), respectively. Higher tumor CASR expression was associated with a lower risk of colorectal cancer-specific mortality. This finding needs further confirmation and if confirmed, may lead to better understanding of the role of CASR in colorectal cancer progression. [ABSTRACT FROM AUTHOR]

Background: The association between soy isoflavones intake and cardiometabolic health remains inconclusive. We investigated the associations of urinary biomarkers of isoflavones including daidzein, glycitein, genistein, equol (a gut microbial metabolite of daidzein), and equol-predicting microbial species with cardiometabolic risk markers., Methods and Results: In a 1-year study of 305 Chinese community-dwelling adults aged ≥18 years, urinary isoflavones, fecal microbiota, blood pressure, blood glucose and lipids, and anthropometric data were measured twice, 1 year apart. Brachial-ankle pulse wave velocity was also measured after 1 year. A linear mixed-effects model was used to analyze repeated measurements. Logistic regression was used to calculate the adjusted odds ratio (aOR) and 95% CI for the associations for arterial stiffness. Each 1 μg/g creatinine increase in urinary equol concentrations was associated with 1.47%, 0.96%, and 3.32% decrease in triglycerides, plasma atherogenic index, and metabolic syndrome score, respectively (all P <0.05), and 0.61% increase in high-density lipoprotein cholesterol ( P =0.025). Urinary equol was also associated with lower risk of arterial stiffness (aOR, 0.28 [95% CI, 0.09-0.90]; P trend =0.036). We identified 21 bacterial genera whose relative abundance was positively associated with urinary equol (false discovery rate-corrected P <0.05) and constructed a microbial species score to reflect the overall equol-predicting capacity. This score (per 1-point increase) was inversely associated with triglycerides (percentage difference=-1.48%), plasma atherogenic index (percentage difference=-0.85%), and the risk of arterial stiffness (aOR, 0.27 [95% CI, 0.08-0.88]; all P <0.05)., Conclusions: Our findings suggest that urinary equol and equol-predicting microbial species may improve cardiometabolic risk parameters in Chinese adults.