Archive

Research Area: Body Weight/Satiety

Almond consumption affects fecal microbiota composition, stool pH, and stool moisture in overweight and obese adults with elevated fasting blood glucose: A randomized controlled trial.

Choo, J.M., C.D. Tran, N.D. Luscombe-Marsh, W. Stonehouse, J. Bowen, N. Johnson, C.H. Thompson, E.-J. Watson, G.D. Brinkworth, G.B. Rogers, 2021. Almond consumption affects fecal microbiota composition, stool pH, and stool moisture in overweight and obese adults with elevated fasting blood glucose: A randomized controlled trial. Nutr Res. 85:47-59.

Regular almond consumption has been shown to improve body weight management, lipid profile and blood glucose control. We hypothesized that almond consumption would alter fecal microbiota composition, including increased abundance and activity of potentially beneficial bacterial taxa in adults who are overweight and obese with elevated fasting blood glucose. A total of 69 adults who were overweight or obese with an elevated plasma glucose (age: 60.8 ± 7.4, BMI ≥27 kg/m2, fasting plasma glucose ≥5.6 to <7.0 mmol/L) were randomized to daily consumption of either 2 servings of almonds (AS:56 g/day) or an isocaloric, high carbohydrate biscuit snack for 8 weeks. AS but not biscuit snack experienced significant changes in microbiota composition (P= .011) and increases in bacterial richness, evenness, and diversity (P< .01). Increases in both the relative and absolute abundance of operational taxonomic units in the Ruminococcaceae family, including Ruminiclostridium (false discovery rate P = .002), Ruminococcaceae NK4A214 (P = .002) and Ruminococcaceae UCG-003 (P = .002) were the principal drivers of microbiota-level changes. No changes in fecal short chain fatty acid levels, or in the carriage of the gene encoding butyryl-CoA:acetate CoA-transferase (an enzyme involved in butyrate synthesis) occurred. Almond consumption was not associated with reduced gut permeability, but fecal pH (P= .0006) and moisture content (P = .027) decreased significantly in AS when compared to BS. Regular almond consumption increased the abundance of potentially beneficial ruminococci in the fecal microbiota in individuals with elevated blood glucose. However, fecal short-chain fatty acid levels remained unaltered and the capacity for such microbiological effects to precipitate host benefit is not known.

Neural correlates of future weight loss reveal a possible role for brain-gastric interactions.

Levakov G, Kaplan A, Yaskolka Meir A, Rinott E, Tsaban G, Zelicha H, Meiran N, Shelef I, Shai I, Avidan G., 2021. Neural correlates of future weight loss reveal a possible role for brain-gastric interactions. Neuroimage. 224:117403. doi: 10.1016/j.neuroimage.2020.117403.

Lifestyle dietary interventions are an essential practice in treating obesity, hence neural factors that may assist in predicting individual treatment success are of great significance. Here, in a prospective, open-label, three arms study, we examined the correlation between brain resting-state functional connectivity measured at baseline and weight loss following 6 months of lifestyle intervention in 92 overweight participants. We report a robust subnetwork composed mainly of sensory and motor cortical regions, whose edges correlated with future weight loss. This effect was found regardless of intervention group. Importantly, this main finding was further corroborated using a stringent connectivity-based prediction model assessed with cross-validation thus attesting to its robustness. The engagement of senso-motor regions in this subnetwork is consistent with the over-sensitivity to food cues theory of weight regulation. Finally, we tested an additional hypothesis regarding the role of brain-gastric interaction in this subnetwork, considering recent findings of a cortical network synchronized with gastric activity. Accordingly, we found a significant spatial overlap with the subnetwork reported in the present study. Moreover, power in the gastric basal electric frequency within our reported subnetwork negatively correlated with future weight loss. This finding was specific to the weight loss related subnetwork and to the gastric basal frequency. These findings should be further corroborated by combining direct recordings of gastric activity in future studies. Taken together, these intriguing results may have important implications for our understanding of the etiology of obesity and the mechanism of response to dietary intervention.

Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial.

Yaskolka M.A., E. Rinott, G. Tsaban, H. Zelicha, A. Kaplan, P. Rosen, I. Shelef, I. Youngster, A. Shalev, M. Blüher, U. Ceglarek, M. Stumvoll, K. Tuohy, C. Diotallevi, U. Vrhovsek, F. Hu, M. Stampfer, I. Shai, 2021. Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial. Gut. 0:1–11. doi:10.1136/gutjnl-2020-323106.

Objective: To examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/ processed meat, and enriched with green plants and polyphenols on non-alcoholic fatty liver disease (NAFLD), reflected by intrahepatic fat (IHF) loss. Design: For the DIRECT-PLUS 18-month randomized clinical trial, we assigned 294 participants with abdominal obesity/dyslipidaemia into healthy dietary guidelines (HDG), MED and green-MED weight-loss diet groups, all accompanied by physical activity. Both isocaloric MED groups consumed 28 g/day walnuts (+440 mg/day polyphenols provided). The green-MED group further consumed green tea (3–4 cups/day) and Mankai (a Wolffia globosa aquatic plant strain; 100 g/ day frozen cubes) green shake (+1240 mg/day total polyphenols provided). IHF% 18-month changes were quantified continuously by proton magnetic resonance spectroscopy (MRS). Results: Participants (age=51 years; 88% men; body mass index=31.3 kg/m2; median IHF%=6.6%; mean=10.2%; 62% with NAFLD) had 89.8% 18 month retention-rate, and 78% had eligible follow-up MRS. Overall, NAFLD prevalence declined to: 54.8% (HDG), 47.9% (MED) and 31.5% (green-MED), p=0.012 between groups.  Despite similar moderate weight-loss in both MED groups, green-MED group achieved almost double IHF% loss (−38.9% proportionally), as compared with MED (−19.6% proportionally; p=0.035 weight loss adjusted) and HDG (−12.2% proportionally; p<0.001). After 18 months, both MED groups had significantly higher total plasma polyphenol levels versus HDG, with higher detection of Naringenin and 2-5-dihydroxybenzoic- acid in green-MED. Greater IHF% loss was independently associated with increased Mankai and walnuts intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, changes in microbiome composition (beta-diversity) and specific bacteria (p<0.05 for all). Conclusion: The new suggested strategy of green-Mediterranean diet, amplified with green plant-based proteins/polyphenols as Mankai, green tea, and walnuts, and restricted in red/processed meat can double IHF loss than other healthy nutritional strategies and reduce NAFLD in half.

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.