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Walnuts and vegetable oils containing oleic acid differentially affect the gut microbiota and associations with cardiovascular risk factors: Follow-up of a randomized, controlled, feeding trial in adults at risk for cardiovascular disease.

Tindall, A.M., C.J. McLimans, K.S. Petersen, P.M. Kris-Etherton, R. Lamendella, 2020. Walnuts and vegetable oils containing oleic acid differentially affect the gut microbiota and associations with cardiovascular risk factors: Follow-up of a randomized, controlled, feeding trial in adults at risk for cardiovascular disease. J Nutr. 2020;150(4):806-817.

Background: It is unclear whether the favorable effects of walnuts on the gut microbiota are attributable to the fatty acids, including α-linolenic acid (ALA), and/or the bioactive compounds and fiber. Objective: This study examined between-diet gut bacterial differences in individuals at increased cardiovascular risk following diets that replace SFAs with walnuts or vegetable oils. Methods: Forty-two adults at cardiovascular risk were included in a randomized, crossover, controlled-feeding trial that provided a 2-wk standard Western diet (SWD) run-in and three 6-wk isocaloric study diets: a diet containing whole walnuts (WD; 57-99 g/d walnuts; 2.7% ALA), a fatty acid-matched diet devoid of walnuts (walnut fatty acid-matched diet; WFMD; 2.6% ALA), and a diet replacing ALA with oleic acid without walnuts (oleic acid replaces ALA diet; ORAD; 0.4% ALA). Fecal samples were collected following the run-in and study diets to assess gut microbiota with 16S rRNA sequencing and Qiime2 for amplicon sequence variant picking. Results: Subjects had elevated BMI (30 ± 1 kg/m2), blood pressure (121 ± 2/77 ± 1 mmHg), and LDL cholesterol (120 ± 5 mg/dL). Following the WD, Roseburia [relative abundance (RA) = 4.2%, linear discriminant analysis (LDA) = 4], Eubacterium eligensgroup (RA = 1.4%, LDA = 4), LachnospiraceaeUCG001 (RA = 1.2%, LDA = 3.2), Lachnospiraceae UCG004 (RA = 1.0%, LDA = 3), and Leuconostocaceae (RA = 0.03%, LDA = 2.8) were most abundant relative to taxa in the SWD (P ≤ 0.05 for all). The WD was also enriched in Gordonibacter relative to the WFMD. Roseburia (3.6%, LDA = 4) and Eubacterium eligensgroup (RA = 1.5%, LDA = 3.4) were abundant following the WFMD, and Clostridialesvadin BB60group (RA = 0.3%, LDA = 2) and gutmetagenome (RA = 0.2%, LDA = 2) were most abundant following the ORAD relative to the SWD (P ≤ 0.05 for all). Lachnospiraceae were inversely correlated with blood pressure and lipid/lipoprotein measurements following the WD. Conclusions: The results indicate similar enrichment of Roseburia following the WD and WFMD, which could be explained by the fatty acid composition. Gordonibacter enrichment and the inverse association between Lachnospiraceae and cardiovascular risk factors following the WD suggest that the gut microbiota may contribute to the health benefits of walnut consumption in adults at cardiovascular risk. This trial was registered at clinicaltrials.gov as NCT02210767.

Walnut consumption and cardiac phenotypes: the coronary artery risk development in young adults (CARDIA) study.  

Steffen, L.M., S.Y. Yi, D. Duprez, X. Zhou, J.M. Shikany, D.R. Jacobs Jr., 2020. Walnut consumption and cardiac phenotypes: the coronary artery risk development in young adults (CARDIA) study.  Nutr Metab Cardiovasc Dis. S0939-4753(20)30381-1. doi: 10.1016/j.numecd.2020.09.001.  

Background and Aims: Observational studies and clinical trials have shown cardiovascular benefits of nut consumption, including walnuts. However, the relations of walnut consumption with systolic and diastolic function, risk factors for heart failure, are unknown.  We examined the associations of walnut consumption with cardiac structure and function parameters in black and white adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Methods and Results: After exclusions, the study population included 3,341 participants. Dietary intake was assessed using the CARDIA Diet History questionnaire at baseline, year 7 and year 20 exams.  Cardiac structure and function were measured by echocardiography at year 25. Multivariable linear regression evaluated the associations of walnut consumption with blood pressure (BP), heart rate, and cardiac phenotypes, adjusting for age, sex, race, lifestyle habits, and clinical characteristics. We found the majority of walnut consumers compared to non-consumers were females, whites, and more highly educated, and had lower waist circumference, diastolic BP, and heart rate, and higher diet quality score. Even though cardiac structure and function measures were generally within normal ranges among participants, walnut consumers had significantly better values for diastolic function parameters A wave, E/A ratio, septal and lateral e’ than non-consumers. Further adjustment for body mass index and diabetes status did not materially change the significance between walnut consumer groups. Systolic function parameters did not differ by walnut group.  Conclusion: Compared to non-consumers, walnut consumption is associated with better diastolic dysfunction in young to middle-aged adults.

Effects of diet-modulated autologous fecal microbiota transplantation on weight regain.

Rinott, E., I. Youngster, A.Y. Meir, G. Tsaban, H. Zelicha, A. Kaplan, D. Knights, K. Tuohy, F. Fava, M.U. Scholz, O. Ziv, E. Reuven, A. Tirosh, A. Rudich, M. Blüher, M. Stumvoll, U. Ceglarek, K. Clement, O. Koren, D.D. Wang, F.B. Hu, M.J. Stampfer, I. Shai, 2020. Effects of diet-modulated autologous fecal microbiota transplantation on weight regain. Gastroenterology. doi: https:// doi.org/10.1053/j.gastro.2020.08.041.

Background & Aims: We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight loss phase. Methods: In the DIRECT-PLUS weight loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to (1) healthy dietary guidelines, (2) Mediterranean diet, and (3) green-Mediterranean diet weight-loss groups. All groups received free gym membership and physical activity guidelines. Both iso-caloric Mediterranean groups consumed 28g/day walnuts (+440mg/d polyphenols provided). The green-Mediterranean dieters further consumed green tea (3-4 cups/day) and a Wolffia-globosa (Mankai strain;100g/day) green shake (+800mg/day polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight regain phase (months 6–14). Secondary outcomes were gastrointestinal symptoms, waist-circumference, glycemic status and changes in the gut microbiome, as measured by metagenomic sequencing and 16s-rRNA. We validated the results in a parallel in-vivo study of mice specifically fed with Mankai, as compared to control chow diet. Results: Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules over the transplantation period. No aFMTrelated adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6–14 (aFMT, 30.4% vs. placebo, 40.6%;P=.28), aFMT significantly attenuated weight regain in the green Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P=.02), but not in the dietary guidelines (P=.57) or Mediterranean diet (P=.64) groups (P for the interaction=.03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89cm vs placebo, 5.05cm;P=.01) and insulin rebound (aFMT, 1.46±3.6µIU/ml vs placebo, 1.64±4.7µIU/ml;P=.04) in the green Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction=.04 and .03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight loss phase, and to prompt preservation of weight loss-associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) following the aFMT. In mice, Mankaimodulated aFMT in the weight loss phase, compared with control diet aFMT, significantly prevented weight regain, and resulted in better glucose tolerance, during a high-fat-diet induced regain phase (P<.05 for all). Conclusions: Autologous FMT, collected during the weight loss phase and administrated in the regain phase, might preserve weight loss and glycemic control and is associated with specific microbiome signatures. High-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure.

Effect of walnut consumption on markers of blood glucose control: A systematic review and meta-analysis.

Neale, E. V. Guan, L. Tapsell, Y. Probst, 2020. Effect of walnut consumption on markers of blood glucose control: A systematic review and meta-analysis. Br J Nutr. 1‐13. doi:10.1017/S0007114520001415

Type 2 diabetes mellitus is a chronic disease increasing in global prevalence. Although habitual consumption of walnuts is associated with reduced risk of CVD, there is inconsistent evidence for the impact of walnut consumption on markers of glycaemic control. This systematic review and meta-analysis aimed to examine the effect of walnut consumption on markers of blood glucose control. A systematic search of Medline, PubMed, CINAHL and Cochrane databases (to 2 March 2019) was conducted. Inclusion criteria were randomised controlled trials conducted with adults which assessed the effect of walnut consumption on fasting blood glucose and insulin, glycated Hb and homeostatic model assessment of insulin resistance. Random effects meta-analyses were conducted to assess the weighted mean differences (WMD) for each outcome. Risk of bias in studies was assessed using the Cochrane Risk of Bias tool 2.0. Sixteen studies providing eighteen effect sizes were included in the review. Consumption of walnuts did not result in significant changes in fasting blood glucose levels (WMD: 0·331 mg/dl; 95 % CI −0·817, 1·479) or other outcome measures. Studies were determined to have either ‘some concerns’ or be at ‘high risk’ of bias. There was no evidence of an effect of walnut consumption on markers of blood glucose control. These findings suggest that the known favourable effects of walnut intake on CVD are not mediated via improvements in glycaemic control. Given the high risk of bias observed in the current evidence base, there is a need for further high-quality randomised controlled trials.