Interactions of dietary fat with the gut microbiota: evaluation of mechanisms and metabolic consequences

The current scientific literature proposes that both the amount and type of dietary fat modulate homeostasis of the gut microbiota; disturbances in homeostasis may have metabolic consequences with potentially serious clinical manifestations. The evidence for interactions between dietary fat and gut microbiota has been mostly derived from animal studies, but there is now also evidence emerging from human studies. We will review the current literature on how dietary fat influences the gut microbiota, particularly focusing on the type of fat. Mechanisms detailing how this crosstalk may impact on host metabolism and health will also be discussed. Some studies have reported somewhat controversial findings and therefore we will evaluate critically which possible aspects should be considered when interpreting current and planning further studies to explore the diet-microbiota crosstalk and its metabolic and clinical implications for the host.</p

Evaluation of serum zonulin for use as an early predictor for gestational diabetes

Diet has an important role in regulating intestinal permeability and subsequently the risk for metabolic disorders. In this observational study, we examined whether serum intestinal permeability marker zonulin, could be used as a predictor for gestational diabetes mellitus (GDM). Serum zonulin concentration was measured in early pregnancy in overweight or obese pregnant women (n = 88) at risk for developing GDM. Serum zonulin was associated with higher odds of GDM (adjusted OR for 1 ng ml(-1) increase in zonulin: 1.08, 95% CI: 1.02-1.15; P = 0.009), diagnosed by a 2-h 75-g oral glucose tolerance test at late pregnancy. The optimal cutoff value was 43.3 ng ml(-1), with sensitivity of 88% (95% CI: 71-100%) and specificity of 47% (95% CI: 33-58%). The area under the ROC-curve was 0.67 (95% CI: 0.54-0.81). Our results show an association between increased earlypregnancy serum zonulin concentration and GDM, suggesting zonulin as a possible predictor for GDM

Early pregnancy serum IGFBP-1 relates to lipid profile in overweight and obese women

Lower level of insulin-like growth factor-binding protein (IGFBP-1) has been observed in insulin resistance, while higher level of matrix metalloproteinase-8 (MMP-8) has been linked to obesity. The aim here was to study in overweight and obese women, typically manifesting with insulin resistance, whether IGFBP-1 and MMP-8 are related to and reflect systemic low-grade inflammation, metabolism and diet. Fasting serum from overweight and obese pregnant women (n = 100) in early pregnancy were analysed for IGFBP-1, phosphorylated IGFBP-1 (phIGFBP-1) and MMP-8. High-sensitivity CRP and GlycA were used as markers for low grade inflammation. GlycA and lipids were quantified using NMR. IGFBP-1 associated negatively with GlycA, evidenced by higher concentrations in the lowest quartile (median 1.53 (IQR 1.45-1.72)) compared to the highest (1.46 (1.39-1.55)) (P = 0.03). Several lipid metabolites, particularly HDL-cholesterol, correlated inversely with phIGFBP-1 (FDR<0.1). Nutritional status and diet contributed to the levels of IGFBP-1, demonstrated as an inverse correlation with maternal weight (Spearman r = -0.205, P = 0.04) and dietary intake of vitamin A (r = -0.253, P = 0.014) and a direct correlation with dietary intake of polyunsaturated fatty acids (Spearman r = 0.222, P = 0.03). MMP-8 correlated inversely with pyridoxine (r = -0.321, P = 0.002) and potassium (r = -0.220, P = 0.033). Maternal serum IGFBP-1 may contribute to maternal lipid metabolism in overweight and obese women during early pregnancy. These findings may be of importance in identification of metabolic disturbances preceding the adverse metabolic outcomes in pregnancy

Distinct Metabolomic Profile Because of Gestational Diabetes and its Treatment Mode in Women with Overweight and Obesity

ObjectiveWhether the presence of gestational diabetes (GDM) and its treatment mode influence the serum metabolic profile in women with overweight or obesity was studied.MethodsThe serum metabolic profiles of 352 women with overweight or obesity participating in a mother‐infant clinical study were analyzed with a targeted NMR approach (at 35.1 median gestational weeks). GDM was diagnosed with a 2‐hour 75‐g oral glucose tolerance test.ResultsThe metabolomic profile of the women with GDM (n = 100) deviated from that of women without GDM (n = 252). Differences were seen in 70 lipid variables, particularly higher concentrations of very low‐density lipoprotein particles and serum triglycerides were related to GDM. Furthermore, levels of branched‐chain amino acids and glycoprotein acetylation, a marker of low‐grade inflammation, were higher in women with GDM. Compared with women with GDM treated with diet only, the women treated with medication (n = 19) had higher concentrations of severalizes of VLDL particles and their components, leucine, and isoleucine, as well as glycoprotein acetylation.ConclusionsA clearly distinct metabolic profile was detected in GDM, which deviated even more if the patient was receiving medical treatment. This suggests a need for more intense follow‐up and therapy for women with GDM during pregnancy and postpartum to reduce their long‐term adverse health risks.</p

Efficacy of Fish Oil and/or Probiotic Intervention on the Incidence of Gestational Diabetes Mellitus in an At-Risk Group of Overweight and Obese Women: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial

OBJECTIVE To assess whether the risk of gestational diabetes mellitus (GDM) may be lowered and glucose metabolism improved by daily administration of fish oil and/or probiotic supplements in overweight and obese pregnant women.RESEARCH DESIGN AND METHODS We randomized in a double-blind manner 439 women (mean 13.9 ± 2.1 gestational weeks [gw]) into four intervention groups: fish oil + placebo, probiotics + placebo, fish oil + probiotics, and placebo + placebo. Fish oil (1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid) and probiotic supplements (Lactobacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each) were provided for daily consumption from randomization beyond delivery. Primary outcomes were the incidence of GDM diagnosed with oral glucose tolerance test targeted at 24–28 gw and the change in fasting glucose between randomization and late pregnancy (mean 35.2 ± 0.9 gw). Insulin concentration, insulin resistance HOMA2-IR index, and pregnancy outcomes were determined, as were adverse effects related to the intervention. Analyses were by intent to treat.RESULTS No differences were found among the intervention groups in the maternal and neonatal pregnancy outcomes or side effects related to the intervention (P > 0.05). The proportion of women with GDM (94 of 377; fish oil + placebo, 23 of 96, 24.0%; probiotics + placebo, 25 of 99, 25.3%; fish oil + probiotics, 26 of 91, 28.6%; and placebo + placebo, 20 of 91, 22.0%) or the change in glucose, insulin, or HOMA2-IR (n = 364) did not differ among the intervention groups (P > 0.11 for all comparisons).CONCLUSIONS An intervention with fish oil and/or probiotics during pregnancy seemed to be both safe and well tolerated but conferred no benefits in lowering the risk of GDM or improving glucose metabolism in overweight and obese women.</div

Weight gain and body composition during pregnancy: A randomized pilot trial with probiotics and/or fish oil

We evaluated the effects of fish oil and/or probiotic supplementation in a randomized placebo-controlled intervention pilot trial on gestational weight gain (GWG) and body composition. Additionally, the influence of gestational diabetes (GDM) on GWG and body composition was assessed. We randomized 439 overweight or obese women (mean 13.9±2.1 gestational weeks) into four intervention groups: fish oil+placebo, probiotics+placebo, fish oil+probiotics and placebo+placebo. Fish oil (1.9g docosahexaenoic acid and 0.22g eicosapentaenoic acid) and probiotic supplements (Lactobacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 CFU each) were consumed daily from randomization until delivery. GDM was diagnosed with 2-hour 75g oral glucose tolerance test. Body composition was measured with air displacement plethysmography at randomization and in late pregnancy (mean 35.2±0.9 gestational weeks). Fish oil and/or probiotic intervention did not influence mean GWG or change in body fat mass or body fat percentage of the women (p>0.17 for all comparisons). Body composition in early pregnancy did not differ between the women who did or did not develop GDM (adjusted p>0.23). Compared to the normoglycemic women (n=278), women diagnosed with GDM (n=119) gained less weight (7.7±0.4kg vs. 9.3±0.4kg, adjusted mean difference -1.66 [-2.52, -0.80],p</p

A carbohydrate-active enzyme (CAZy) profile links successful metabolic specialization of Prevotella to its abundance in gut microbiota

Gut microbiota participates in diverse metabolic and homeostatic functions related to health and well-being. Its composition varies between individuals, and depends on factors related to host and microbial communities, which need to adapt to utilize various nutrients present in gut environment. We profiled fecal microbiota in 63 healthy adult individuals using metaproteomics, and focused on microbial CAZy (carbohydrate-active) enzymes involved in glycan foraging. We identified two distinct CAZy profiles, one with many Bacteroides-derived CAZy in more than one-third of subjects (n = 25), and it associated with high abundance of Bacteroides in most subjects. In a smaller subset of donors (n = 8) with dietary parameters similar to others, microbiota showed intense expression of Prevotella-derived CAZy including exo-beta-(1,4)-xylanase, xylan-1,4-beta-xylosidase, alpha-L-arabinofuranosidase and several other CAZy belonging to glycosyl hydrolase families involved in digestion of complex plant-derived polysaccharides. This associated invariably with high abundance of Prevotella in gut microbiota, while in subjects with lower abundance of Prevotella, microbiota showed no Prevotella-derived CAZy. Identification of Bacteroides- and Prevotella-derived CAZy in microbiota proteome and their association with differences in microbiota composition are in evidence of individual variation in metabolic specialization of gut microbes affecting their colonizing competence

Metagenomics analysis of gut microbiota in response to diet intervention and gestational diabetes in overweight and obese women: a randomised, double-blind, placebo-controlled clinical trial

Objective: Gut microbiota and diet are known to contribute to human metabolism. We investigated whether the metagenomic gut microbiota composition and function changes over pregnancy are related to gestational diabetes mellitus (GDM) and can be modified by dietary supplements, fish oil and/or probiotics.Design: The gut microbiota of 270 overweight/obese women participating in a mother-infant clinical study were analysed with metagenomics approach in early (mean gestational weeks 13.9) and late (gestational weeks 35.2) pregnancy. GDM was diagnosed with a 2 hour 75 g oral glucose tolerance test.Results: Unlike women with GDM, women without GDM manifested changes in relative abundance of bacterial species over the pregnancy, particularly those receiving the fish oil + probiotics combination. The specific bacterial species or function did not predict the onset of GDM nor did it differ according to GDM status, except for the higher abundance of Ruminococcus obeum in late pregnancy in the combination group in women with GDM compared with women without GDM. In the combination group, weak decreases over the pregnancy were observed in basic bacterial housekeeping functions.Conclusions: The specific gut microbiota species do not contribute to GDM in overweight/obese women. Nevertheless, the GDM status may disturb maternal gut microbiota flexibility and thus limit the capacity of women with GDM to respond to diet, as evidenced by alterations in gut microbiota observed only in women without GDM. These findings may be important when considering the metabolic complications during pregnancy, but further studies with larger populations are called for to verify the findings.</p

Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota

Gut microbiota-related metabolites are potential clinical biomarkers for cardiovascular disease (CVD). Circulating succinate, a metabolite produced by both microbiota and the host, is increased in hypertension, ischemic heart disease, and type 2 diabetes. We aimed to analyze systemic levels of succinate in obesity, a major risk factor for CVD, and its relationship with gut microbiome. We explored the association of circulating succinate with specific metagenomic signatures in cross-sectional and prospective cohorts of Caucasian Spanish subjects. Obesity was associated with elevated levels of circulating succinate concomitant with impaired glucose metabolism. This increase was associated with specific changes in gut microbiota related to succinate metabolism: a higher relative abundance of succinate-producing Prevotellaceae (P) and Veillonellaceae (V), and a lower relative abundance of succinate-consuming Odoribacteraceae (O) and Clostridaceae (C) in obese individuals, with the (P + V/O + C) ratio being a main determinant of plasma succinate. Weight loss intervention decreased (P + V/O + C) ratio coincident with the reduction in circulating succinate. In the spontaneous evolution after good dietary advice, alterations in circulating succinate levels were linked to specific metagenomic signatures associated with carbohydrate metabolism and energy production with independence of body weight change. Our data support the importance of microbe-microbe interactions for the metabolite signature of gut microbiome and uncover succinate as a potential microbiota-derived metabolite related to CVD risk

Opportunities for probiotics and polyunsaturated fatty acids to improve metabolic health of overweight pregnant women

Overweight during pregnancy predisposes both the mother and foetus to health complications. Maternal complications include gestational diabetes, obstetric problems and type 2 diabetes later in life. Complications for the offspring are not only restricted to the foetal period or birth, such as prematurity and foetal macrosomia, but may also have long-term metabolic health implications through the mechanism of early nutrition programming. One of the key metabolic components characterising overweight in the non-pregnant state is low-grade inflammation manifested by elevated levels of circulatory pro-inflammatory cytokines. In pregnancy, in addition to adipose tissue and placenta, inflammatory response may originate from the gut. The extent to which overweight induces metabolic maladaptation during pregnancy and further compromises maternal and child health is currently poorly understood. In this review, we evaluate recent scientific literature and describe the suggested links between overweight, gut and low-grade inflammation associated metabolic disorders. We focus on overweight pregnant women and gestational diabetes, and discuss how specific dietary factors, probiotics and long-chain polyunsaturated fatty acids (fish oil), might confer health benefits in combatting against metabolic risk factors.</p