Changes in Gut Microbiota–Related Metabolites and Long-term Successful Weight Loss in Response to Weight-Loss Diets: The POUNDS Lost Trial

Heianza, Yoriko; Sun, Dianjianyi; Smith, Steven R.; Bray, George A.; Sacks, Frank M.; Qi, Lü

doi:10.2337/dc17-2108

Cited by 65 publications

(62 citation statements)

References 43 publications

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“…There were no significant differences in mean values of body mass index (BMI), fasting glucose, fasting insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) at the baseline examination between participants who were included (n=510) or those who were not included (n=301) in the present analysis. As we described previously,26 the baseline median (25th, 75th) values of each metabolite were 2.7 (1.8, 3.8) µM for TMAO, 8.6 (7.4, 10.3) µM for choline and 34.5 (30.0, 39.3) µM for L-carnitine among the 510 participants. Since a few participants (n=6) had missing data on fasting insulin, haemoglobin A1c (HbA1c) or 6-month changes in serum amino acid metabolites, these were excluded from the present analysis.…”

Section: Methodssupporting

confidence: 57%

“…On the other hand, L-carnitine supplementation has been suggested to improve glycaemic control in patients with type 2 diabetes 46. We have recently reported that changes in choline and L-carnitine were significantly associated with improvements in adiposity measurements 26. In the present study, we found that the adjustment for concurrent weight changes weakened the associations of choline or L-carnitine with insulin resistance.…”

Section: Discussionsupporting

confidence: 44%

“…As to the potential explanations for these findings, the TMAO-generating FMO3 plays roles in regulating obesity37 and the beiging of white adipose tissue 7. Changes in TMAO levels might also be affected by degrees of weight loss in our study participants 26. Additionally, the FMO3 is suppressed by insulin, and also increased by glucagon37 which is secreted from pancreatic α-cells to promote the elevation of blood glucose 39.…”

Section: Discussionmentioning

confidence: 78%

“…We assessed changes (Δ) in TMAO, choline and L-carnitine from the baseline examination to 6 months of the diet intervention. In our previous study, there were no significant differences in mean or median values of ΔTMAO, Δcholine or ΔL-carnitine across the different diets varying in fat, protein or carbohydrate 26. The ΔTMAO was weakly correlated with Δcholine (Pearson correlation coefficient (r)=0.15, p=0.0006) or with ΔL-carnitine (r=0.14, p=0.002).…”

Section: Methodsmentioning

confidence: 75%

“…Although evidence has consistently demonstrated that various weight-loss diets are effective for the improvement of glucose metabolism and the prevention of diabetes,24 25 little has been clarified as to whether changes in microbial metabolites play a significant role in such protective effects. We have recently reported associations of changes in TMAO, choline and L-carnitine with achieving successful weight loss among overweight and obese adults who participated in a weight-loss diet intervention trial 26. However, whether diet-induced changes in the microbial metabolites are related to the improvements in glucose metabolism remains unclarified.…”

Section: Introductionmentioning

confidence: 99%

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Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial

Heianza

Sun

et al. 2018

Gut

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135

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ObjectiveAlterations in gut microbiota have been linked to host insulin resistance, diabetes and impaired amino acid metabolism. We investigated whether changes in gut microbiota-dependent metabolite of trimethylamine N-oxide (TMAO) and its nutrient precursors (choline and L-carnitine) were associated with improvements in glucose metabolism and diabetes-related amino acids in a weight-loss diet intervention.DesignWe included 504 overweight and obese adults who were randomly assigned to one of four energy-reduced diets varying in macronutrient intake. The 6-month changes (Δ) in TMAO, choline and L-carnitine levels after the intervention were calculated.ResultsGreater decreases in choline and L-carnitine were significantly (p<0.05) associated with greater improvements in fasting insulin concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) at 6 months. The reduction of choline was significantly related to 2-year improvements in glucose and insulin resistance. We found significant linkages between dietary fat intake and ΔTMAO for changes in fasting glucose, insulin and HOMA-IR (pinteraction <0.05); a greater increase in TMAO was related to lesser improvements in the outcomes among participants who consumed a high-fat diet. In addition, ΔL-carnitine and Δcholine were significantly related to changes in amino acids (including branched-chain and aromatic amino acids). Interestingly, the associations of ΔTMAO, Δcholine and ΔL-carnitine with diabetes-related traits were independent of the changes in amino acids.ConclusionOur findings underscore the importance of changes in TMAO, choline and L-carnitine in improving insulin sensitivity during a weight-loss intervention for obese patients. Dietary fat intake may modify the associations of TMAO with insulin sensitivity and glucose metabolism.Trial registration numberNCT00072995.

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Section: Methodssupporting

confidence: 57%

Section: Discussionsupporting

confidence: 44%

Section: Discussionmentioning

confidence: 78%

Section: Methodsmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

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Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial

Heianza

Sun

et al. 2018

Gut

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135

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Investigation of serum trimethylamine‐N‐oxide levels in missed abortion: A prospective study

Sarikaya,

Körez,

Ovali

et al. 2023

Intl J Gynecology & Obste

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ObjectiveThe aim of our study was to investigate the relationship between missed abortion and serum trimethylamine N‐oxide (TMAO) levels.MethodsA total of 129 patients with 56 missed abortions and 73 healthy pregnancies were included in our study. Patients who had more than one pregnancy loss, had systemic disease (hypertension, diabetes, rheumatologic disease, hematologic disease, and so forth) and did not accept to participate in the study were excluded. Pregnant women who did not have a fetal heartbeat in the first 20th week of pregnancy were considered as missed abortion. Demographic characteristics of the patients were recorded. The serum TMAO levels of these patients were compared with the serum TMAO levels of healthy pregnant women with the same gestational week between the two groups.ResultsThe median (IQR) serum level of TMAO was significantly higher in woman with missed abortus compared to the healthy controls (201.5 [IQR, 129.75–345] vs 150 [IQR, 86.9–273], U = 1534, P = 0.015, rrb = 0.25 [95% CI: 0.05–0.43]). We observed a positive and significant relationship between serum TMAO levels and age of the patients (Spearman's rho = 0.272 [95% CI: 0.01–0.50], P = 0.043). However, no significant relationship was found between serum TMAO levels and BMI (Spearman's rho = 0.093 [95% CI: −0.18 to 0.35], P = 0.496).ConclusionIn our study, we found that the serum TMAO level was higher in patients with missed abortion compared to healthy pregnancies. Serum TMAO levels measured at early gestational weeks can provide information about the course of pregnancy.

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Gut and obesity/metabolic disease: Focus on microbiota metabolites

Lin

Zhu

2022

MedComm

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Obesity is often associated with the risk of chronic inflammation and other metabolic diseases, such as diabetes, cardiovascular disease, and cancer. The composition and activity of the gut microbiota play an important role in this process, affecting a range of physiological processes, such as nutrient absorption and energy metabolism. The active gut microbiota can produce a large number of physiologically active substances during the process of intestinal metabolism and reproduction, including short‐chain/long‐chain fatty acids, secondary bile acids, and tryptophan metabolites with beneficial effects on metabolism, as well as negative metabolites, including trimethylamine N‐oxide, delta‐valerobetaine, and imidazole propionate. How gut microbiota specifically affect and participate in metabolic and immune activities, especially the metabolites directly produced by gut microbiota, has attracted extensive attention. So far, some animal and human studies have shown that gut microbiota metabolites are correlated with host obesity, energy metabolism, and inflammation. Some pathways and mechanisms are slowly being discovered. Here, we will focus on the important metabolites of gut microbiota (beneficial and negative), and review their roles and mechanisms in obesity and related metabolic diseases, hoping to provide a new perspective for the treatment and remission of obesity and other metabolic diseases from the perspective of metabolites.

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Changes in Gut Microbiota–Related Metabolites and Long-term Successful Weight Loss in Response to Weight-Loss Diets: The POUNDS Lost Trial

Cited by 65 publications

References 43 publications

Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial

Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial

Investigation of serum trimethylamine‐N‐oxide levels in missed abortion: A prospective study

Gut and obesity/metabolic disease: Focus on microbiota metabolites

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