Urinary equol and equol-predicting microbial species are favorably associated with body fat measures among Chinese adults.

BACKGROUND: Many studies have investigated the intake of dietary isoflavones in relation to obesity risk, while the association using objective biomarkers of isoflavones, particularly equol (a gut-derived metabolite of daidzein with greater bioavailability than other isoflavones) has been less studied. In addition, the associations between equol and gut microbiota profile at population level remain to be fully characterized. OBJECTIVE: We aimed to identify equol-predicting microbial species and to investigate the associations of equol-predicting microbial species and urinary excretion of isoflavones including glycitein, genistein, daidzein, and equol with diverse obesity markers in free living-individuals. METHODS: In this 1-year longitudinal study of 754 community-dwelling adults, urinary isoflavones, fecal microbiota, height, weight, and circumferences of waist and hip were measured at baseline and again after 1-year. Liver fat [indicated by controlled attenuation parameter (CAP)] and other body composition were also measured after 1-year. Linear models and linear mixed-effects models were used to analyze the associations for single measure and repeated measures, respectively. RESULTS: Among 305 participants (median age: 50 y, IQR: 37-59 y) including 138 men and 167 women, higher urinary excretion of equol was associated with lower CAP (ß = -0.013, P < 0.001) and body fat mass (ß= -0.014, P = 0.046). No association was found between any other urinary isoflavones and obesity markers (all P>0.05). We identified 21 bacterial genera whose relative abundance were positively associated with urinary equol concentrations (all Pfalsediscovery rate < 0.05), and constructed an equol-predicting microbial score to reflect the overall equol-producing potential of host gut microbiota. This score was inversely associated with CAP (ß = -0.040, P = 0.011). CONCLUSIONS: High urinary equol concentrations and equol-predicting microbial species could be favorably associated with liver fat and other obesity markers.

Dynamic changes in tRNA modifications and abundance during T cell activation.

The tRNA pool determines the efficiency, throughput, and accuracy of translation. Previous studies have identified dynamic changes in the tRNA (transfer RNA) supply and mRNA (messenger RNA) demand during cancerous proliferation. Yet dynamic changes may also occur during physiologically normal proliferation, and these are less well characterized. We examined the tRNA and mRNA pools of T cells during their vigorous proliferation and differentiation upon triggering their antigen receptor. We observed a global signature of switch in demand for codons at the early proliferation phase of the response, accompanied by corresponding changes in tRNA expression levels. In the later phase, upon differentiation, the response of the tRNA pool relaxed back to the basal level, potentially restraining excessive proliferation. Sequencing of tRNAs allowed us to evaluate their diverse base-modifications. We found that two types of tRNA modifications, wybutosine and ms2t6A, are reduced dramatically during T cell activation. These modifications occur in the anticodon loops of two tRNAs that decode "slippery codons," which are prone to ribosomal frameshifting. Attenuation of these frameshift-protective modifications is expected to increase the potential for proteome-wide frameshifting during T cell proliferation. Indeed, human cell lines deleted of a wybutosine writer showed increased ribosomal frameshifting, as detected with an HIV gag-pol frameshifting site reporter. These results may explain HIV's specific tropism toward proliferating T cells since it requires ribosomal frameshift exactly on the corresponding codon for infection. The changes in tRNA expression and modifications uncover a layer of translation regulation during T cell proliferation and expose a potential tradeoff between cellular growth and translation fidelity.

Association between time-restricted eating and non-alcoholic fatty liver disease in a nationwide cross-sectional study.

The association between time-restricted eating (TRE) and the risk of non-alcoholic fatty liver disease (NAFLD) is less studied. Moreover, whether the association is independent of physical exercise or diet quality or quantity is uncertain. In this nationwide cross-sectional study of 3813 participants, the timing of food intakes was recorded by 24-h recalls; NAFLD was defined through vibration-controlled transient elastography in the absence of other causes of chronic liver disease. OR and 95 % CI were estimated using logistic regression. Participants with daily eating window of ≤ 8 h had lower odds of NAFLD (OR = 0·70, 95 % CI: 0·52, 0·93), compared with those with ≥ 10 h window. Early (05.00-15.00) and late TRE (11.00-21.00) showed inverse associations with NAFLD prevalence without statistical heterogeneity (Pheterogeneity = 0·649) with OR of 0·73 (95 % CI: 0·36, 1·47) and 0·61 (95 % CI: 0·44, 0·84), respectively. Such inverse association seemed stronger in participants with lower energy intake (OR = 0·58, 95 % CI: 0·38, 0·89, Pinteraction = 0·020). There are no statistical differences in the TRE-NAFLD associations according to physical activity (Pinteraction = 0·390) or diet quality (Pinteraction = 0·110). TRE might be associated with lower likelihood of NAFLD. Such inverse association is independent of physical activity and diet quality and appears stronger in individuals consuming lower energy. Given the potential misclassification of TRE based on one- or two-day recall in the analysis, epidemiological studies with validated methods for measuring the habitual timing of dietary intake are warranted.

An engineered genetic circuit for lactose intolerance alleviation.

BACKGROUND: Lactose malabsorption occurs in around 68% of the world's population, causing lactose intolerance (LI) symptoms, such as abdominal pain, bloating, and diarrhea. To alleviate LI, previous studies have mainly focused on strengthening intestinal ß-galactosidase activity while neglecting the inconspicuous drop in the colon pH caused by the fermentation of non-hydrolyzed lactose by the gut microbes. A drop in colon pH will reduce the intestinal ß-galactosidase activity and influence intestinal homeostasis. RESULTS: Here, we synthesized a tri-stable-switch circuit equipped with high ß-galactosidase activity and pH rescue ability. This circuit can switch in functionality between the expression of ß-galactosidase and expression of L-lactate dehydrogenase in response to an intestinal lactose signal and intestinal pH signal, respectively. We confirmed that the circuit functionality was efficient in bacterial cultures at a range of pH levels, and in preventing a drop in pH and ß-galactosidase activity after lactose administration to mice. An impact of the circuit on gut microbiota composition was also indicated. CONCLUSIONS: Due to its ability to flexibly adapt to environmental variation, in particular to stabilize colon pH and maintain ß-galactosidase activity after lactose influx, the tri-stable-switch circuit can serve as a promising prototype for the relief of lactose intolerance.

The Effect of tRNA[Ser]Sec Isopentenylation on Selenoprotein Expression.

Transfer RNA[Ser]Sec carries multiple post-transcriptional modifications. The A37G mutation in tRNA[Ser]Sec abrogates isopentenylation of base 37 and has a profound effect on selenoprotein expression in mice. Patients with a homozygous pathogenic p.R323Q variant in tRNA-isopentenyl-transferase (TRIT1) show a severe neurological disorder, and hence we wondered whether selenoprotein expression was impaired. Patient fibroblasts with the homozygous p.R323Q variant did not show a general decrease in selenoprotein expression. However, recombinant human TRIT1R323Q had significantly diminished activities towards several tRNA substrates in vitro. We thus engineered mice conditionally deficient in Trit1 in hepatocytes and neurons. Mass-spectrometry revealed that hypermodification of U34 to mcm5Um occurs independently of isopentenylation of A37 in tRNA[Ser]Sec. Western blotting and 75Se metabolic labeling showed only moderate effects on selenoprotein levels and 75Se incorporation. A detailed analysis of Trit1-deficient liver using ribosomal profiling demonstrated that UGA/Sec re-coding was moderately affected in Selenop, Txnrd1, and Sephs2, but not in Gpx1. 2'O-methylation of U34 in tRNA[Ser]Sec depends on FTSJ1, but does not affect UGA/Sec re-coding in selenoprotein translation. Taken together, our results show that a lack of isopentenylation of tRNA[Ser]Sec affects UGA/Sec read-through but differs from a A37G mutation.

A New Coumarin-Acridone Compound as a Fluorescence Probe for Fe3+ and Its Application in Living Cells and Zebrafish.

A new coumarin-acridone fluorescent probe S was designed and synthesized, and the structure was confirmed with 1H/13C NMR spectrometry, single-crystal X-ray diffraction, and high-resolution mass spectrometry. This probe has high sensitivity and selectivity for Fe3+ over other testing metal ions at 420 or 436 nm in acetonitrile-MOPS (3-Morpholinopropanesulfonic Acid) buffer solution (20.0 µM, pH = 6.9, 8:2 (v/v)). Under physiological conditions, the probe displayed satisfying time stability with a detection limit of 1.77 µM. In addition, probe S was successfully used to detect intracellular iron changes through a fluorescence-off mode, and the imaging results of cells and zebrafish confirmed their low cytotoxicity and satisfactory cell membrane permeability, as well as their potential biological applications.

Urinary Equol and Equol-Predicting Microbial Species Are Favorably Associated With Cardiometabolic Risk Markers in Chinese Adults.

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]; Ptrend=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.

Urinary enterolignans and enterolignan-predicting microbial species are favourably associated with liver fat and other obesity markers.

Aims: Plant-derived lignans may protect against obesity, while their bioactivity needs gut microbial conversion to enterolignans. We used repeated measures to identify enterolignan-predicting microbial species and investigate whether enterolignans and enterolignan-predicting microbial species are associated with obesity. Methods: Urinary enterolignans, fecal microbiota, body weight, height, and circumferences of the waist (WC) and hips (HC) were repeatedly measured at the baseline and after 1 year in 305 community-dwelling adults in Huoshan, China. Body composition and liver fat [indicated by the controlled attenuation parameter (CAP)] were measured after 1 year. Multivariate-adjusted linear models and linear mixed-effects models were used to analyze single and repeated measurements, respectively. Results: Enterolactone and enterodiol levels were both inversely associated with the waist-to-hip ratio, body fat mass (BFM), visceral fat level (VFL), and liver fat accumulation (all P < 0.05). Enterolactone levels were also associated with lower WC (ß = -0.0035 and P = 0.013) and HC (ß = -0.0028 and P = 0.044). We identified multiple bacterial genera whose relative abundance was positively associated with the levels of enterolactone (26 genera) and enterodiol (22 genera, all P false discovery rate < 0.05), and constructed the enterolactone-predicting microbial score and enterodiol-predicting microbial score to reflect the overall enterolignan-producing potential of the host gut microbiota. Both these scores were associated with lower body weight and CAP (all P < 0.05). The enterolactone-predicting microbial score was also inversely associated with the BFM (ß = -0.1128 and P = 0.027) and VFL (ß = -0.1265 and P = 0.044). Conclusion: Our findings support that modulating the host gut microbiome could be a potential strategy to prevent obesity by enhancing the production of enterolignans.

Metabolic and Risk Profiles of Lean and Non-Lean Hepatic Steatosis among US Adults.

Hepatic steatosis can occur in lean individuals, while its metabolic and risk profiles remain unclear. We aimed to characterize the clinical and risk profiles of lean and non-lean steatosis. This cross-sectional study included 1610 patients with transient elastography-assessed steatosis. The metabolic and risk profiles were compared. Compared to their non-lean counterparts, lean subjects with steatosis had a lower degree of fibrosis (F0-F1: 91.9% vs. 80.9%), had a lower prevalence of diabetes (27.9% vs. 32.8%), dyslipidemia (54.7% vs. 60.2%) and hypertension (50.0% vs. 51.3%), and had higher levels of high-density lipoprotein cholesterol while lower fasting insulin and homeostatic model assessment for insulin resistance (all p < 0.05). Of the 16 potential risk factors, being Hispanic was associated with higher odds of non-lean steatosis but not with lean steatosis (odds ratio (OR): 2.07 vs. 0.93), while excessive alcohol consumption had a different trend in the ratio (OR: 1.47 vs.6.65). Higher waist-to-hip ratio (OR: 7.48 vs. 2.45), and higher waist circumference (OR: 1.14 vs. 1.07) showed a stronger positive association with lean steatosis than with non-lean steatosis (all Pheterogeneity < 0.05). Although lean individuals with steatosis presented a healthier metabolic profile, both lean and non-lean steatosis had a significant proportion of metabolic derangements. In addition, the etiological heterogeneity between lean and non-lean steatosis may exist.

Dietary fiber intake and non-alcoholic fatty liver disease: The mediating role of obesity.

Background and aims: Dietary pattern rich in fiber is negatively associated with the risk of non-alcoholic fatty liver disease (NAFLD). Meanwhile, obesity is a known predisposing factor for NAFLD. Nutrient-focused research can enhance the mechanistic understanding of dietary effects. We thus hypothesized that higher dietary fiber intake was associated with lower risk of NAFLD through the mediating role of obesity. Methods: In this nationwide cross-sectional study, dietary fiber was surveyed using two 24-h recalls. NAFLD and clinically significant fibrosis (CSF) were determined by vibration-controlled transient elastography. Multivariable logistic and linear regression were applied to investigate the association of dietary fiber with NAFLD, CSF, and liver function parameters. We used counterfactual-based mediation analysis to estimate the direct and indirect effect of dietary fiber on NAFLD. Results: Of the 3,974 participants, ~36.86% and 7.78% of participants were diagnosed with NAFLD and CSF. Compared with participants among the lowest tertile, the highest tertile of dietary fiber consumption was associated with lower odds of NAFLD (OR = 0.81; 95% CI: 0.66-0.98; P overall = 0.019). Dietary fiber intake appeared to be linked with lower odds of CSF (OR Tertile3vs.Tertile1 = 0.81; 95% CI: 0.58-1.14; P overall = 0.107). Mediation analysis showed that obesity fully mediated the association of dietary fiber with NAFLD. Dietary fiber was associated with improved hepatic parameters. Conclusions: The findings indicated that increasing dietary fiber intake could confer a greater benefit to protect against NAFLD. Translating these findings regarding dietary fiber into dietary advice might be an attractive strategy for NAFLD prevention.

Higher Adherence to Healthy Lifestyle Score Is Associated with Lower Odds of Non-Alcoholic Fatty Liver Disease.

Growing evidence supports that individual lifestyle factors contribute to the development of non-alcoholic fatty liver disease (NAFLD) without considering the coexistence and synergistic effect of lifestyle factors. Our aim is to derive a healthy lifestyle score (HLS) and estimate its association with NAFLD. In this nationwide cross-sectional study, we derived a five-item HLS including dietary pattern, body mass index, physical activity, cigarette smoking, and sleep duration. NAFLD and clinically significant fibrosis (CSF) were assessed based on vibration-controlled transient elastography (VCTE). Liver function parameters were also tested. Multivariable logistic and linear regressions were applied to investigate the association between HLS and liver diseases. Of the 3893 participants with VCTE examination, approximately 14.1% of participants possessed zero or one healthy lifestyle, 62.5% possessed two or three healthy lifestyles, and 23.4% possessed four or five healthy lifestyles. Compared with participants with a low HLS (0−1 score), the adjusted odds ratios and 95% confidence intervals for those with a high HLS (4−5 score) were 0.25 (0.19~0.33, Ptrend < 0.001) for NAFLD and 0.30 (0.18~0.50, Ptrend < 0.001) for CSF. HLS was positively associated with albumin, total protein, and total bilirubin (all Ptrend ≤ 0.001), and was inversely associated with globulin, alanine aminotransferase, and gamma-glutamyl transaminase (all Ptrend ≤ 0.003). Higher adherence to HLS is associated with lower odds of NAFLD and CSF and may improve liver function. Strategies for the promotion of a healthy lifestyle should be considered as part of NAFLD prevention.

Whole-Genome Identification and Expression Pattern of the Vicinal Oxygen Chelate Family in Rapeseed (Brassica napus L.).

Vicinal oxygen chelate proteins (VOC) are members of the metalloenzyme superfamily, which plays roles in many biological reactions. Some members of the VOC superfamily have been systematically characterized but not in Brassica napus. In this study, 38 VOC genes were identified based on their conserved domains. The present results revealed that most of the BnaVOC genes have few introns, and all contained the typical VOC structure of ßαßßß modules. The BnaVOC genes are distributed unevenly across 15 chromosomes in B. napus and occur as gene clusters on chromosomes C5 and A6. The synteny and phylogenetic analyses revealed that the VOC gene family is a consequence of mesopolyploidy events that occurred in Brassica evolution, and whole-genome duplication and segmental duplication played a major role in the expansion of the BnaVOC gene family. The expression profile analysis indicated that the expression of most BnaVOCs was increased in the leaves and late stage seeds. Further results indicated that seeds of B. napus with a high oil content show higher expression levels under drought stress conditions, suggesting that BnaVOCs not only respond to abiotic stress but may also affect lipid metabolism in drought stress. This present study provides a comprehensive overview of the VOC gene family and provides new insights into their biological function in B. napus evolution.