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Combined berberine and probiotic treatment as an effective regimen for improving postprandial hyperlipidemia in type 2 diabetes patients: a double blinded placebo controlled randomized study.
Wang, S, Ren, H, Zhong, H, Zhao, X, Li, C, Ma, J, Gu, X, Xue, Y, Huang, S, Yang, J, et al
Gut microbes. 2022;14(1):2003176
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Hyperlipidaemia is a major risk factor for atherosclerotic cardiovascular diseases particularly when combined with hyperglycaemia and type 2 diabetes (T2D). Current diagnostic criteria and treatment targets are based on evaluating fasting lipidaemia (FL). However, increasing evidence has supported that a high level of non-fasting lipidaemia, mainly constituted by post-prandial lipidaemia (PL), is also an important CVD risk factor. The aim of this study was to investigate how the combination treatment of berberine (BBR) and probiotics (Prob), or either one could exert benefit on lowering PL, and whether their impact on gut microbiota could contribute to this effect. This study is based on the PREMOTE trial, which was a randomised, double-blind, placebo-controlled clinical trial in 20 medical centres in China and enrolled newly diagnosed T2D patients. This lipidomic study included 365 of the 409 participants enrolled for the PREMOTE trial. Results showed that: - Prob+BBR combined therapy exerted a similar effect on reducing fasting lipidaemia with BBR alone but a superior effect on the levels of postprandial plasma total cholesterol and post-prandial low-density lipoprotein cholesterol compared to either BBR or Prob alone. - a substantial decrease in various lipid species after Prob+BBR treatment. Authors conclude that their findings proved the therapeutic effect of a combined treatment of oral administration of probiotics with berberine on improving PL in patients newly diagnosed with T2D and proposed a new gut microbiome related remedy for managing dyslipidaemia, covering both PL and FL, in patients with T2D.
Abstract
Non-fasting lipidemia (nFL), mainly contributed by postprandial lipidemia (PL), has recently been recognized as an important cardiovascular disease (CVD) risk as fasting lipidemia (FL). PL serves as a common feature of dyslipidemia in Type 2 Diabetes (T2D), albeit effective therapies targeting on PL were limited. In this study, we aimed to evaluate whether the therapy combining probiotics (Prob) and berberine (BBR), a proven antidiabetic and hypolipidemic regimen via altering gut microbiome, could effectively reduce PL in T2D and to explore the underlying mechanism. Blood PL (120 min after taking 100 g standard carbohydrate meal) was examined in 365 participants with T2D from the Probiotics and BBR on the Efficacy and Change of Gut Microbiota in Patients with Newly Diagnosed Type 2 Diabetes (PREMOTE study), a random, placebo-controlled, and multicenter clinical trial. Prob+BBR was superior to BBR or Prob alone in improving postprandial total cholesterol (pTC) and low-density lipoprotein cholesterol (pLDLc) levels with decrement of multiple species of postprandial lipidomic metabolites after 3 months follow-up. This effect was linked to the changes of fecal Bifidobacterium breve level responding to BBR alone or Prob+BBR treatment. Four fadD genes encoding long-chain acyl-CoA synthetase were identified in the genome of this B. breve strain, and transcriptionally activated by BBR. In vitro BBR treatment further decreased the concentration of FFA in the culture medium of B. breve compared to vehicle. Thus, the activation of fadD by BBR could enhance FFA import and mobilization in B. breve and diliminish the intraluminal lipids for absorption to mediate the effect of Prob+BBR on PL. Our study confirmed that BBR and Prob (B. breve) could exert a synergistic hypolipidemic effect on PL, acting as a gut lipid sink to achieve better lipidemia and CVD risk control in T2D.
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Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake.
Meslier, V, Laiola, M, Roager, HM, De Filippis, F, Roume, H, Quinquis, B, Giacco, R, Mennella, I, Ferracane, R, Pons, N, et al
Gut. 2020;69(7):1258-1268
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Evidence suggests that the Mediterranean diet (MD) may help prevent cardiovascular disease (CVD). However, this could be influenced by an individual’s gut microbiome, highlighting a need for personalised nutrition practices. This randomised crossover control trial aimed to evaluate an 8-week personalised MD intervention in 82 overweight and obese subjects, who were at high risk of cardiovascular disease. The results showed that a personalised MD lowered cholesterol, regardless of the amount of energy consumed and the amount of exercise performed and relied upon adherence to the MD. Gut microbiome composition was altered by a MD and although markers for diabetes were not improved overall, there was an improvement in prediabetes in individuals with higher levels of Bacteroides species and lower levels of Prevotella species. It was concluded that a MD may reduce cholesterol and alter the gut microbiome to benefit cardiovascular health. Health professionals could use this study to switch patients to a MD whilst maintaining their energy intake to reduce cardiovascular risk. In order to see maximum benefit, it would be recommended to take a personalised approach and analyse an individual’s gut microbiome in order to tailor recommendations.
Abstract
OBJECTIVES This study aimed to explore the effects of an isocaloric Mediterranean diet (MD) intervention on metabolic health, gut microbiome and systemic metabolome in subjects with lifestyle risk factors for metabolic disease. DESIGN Eighty-two healthy overweight and obese subjects with a habitually low intake of fruit and vegetables and a sedentary lifestyle participated in a parallel 8-week randomised controlled trial. Forty-three participants consumed an MD tailored to their habitual energy intakes (MedD), and 39 maintained their regular diets (ConD). Dietary adherence, metabolic parameters, gut microbiome and systemic metabolome were monitored over the study period. RESULTS Increased MD adherence in the MedD group successfully reprogrammed subjects' intake of fibre and animal proteins. Compliance was confirmed by lowered levels of carnitine in plasma and urine. Significant reductions in plasma cholesterol (primary outcome) and faecal bile acids occurred in the MedD compared with the ConD group. Shotgun metagenomics showed gut microbiome changes that reflected individual MD adherence and increase in gene richness in participants who reduced systemic inflammation over the intervention. The MD intervention led to increased levels of the fibre-degrading Faecalibacterium prausnitzii and of genes for microbial carbohydrate degradation linked to butyrate metabolism. The dietary changes in the MedD group led to increased urinary urolithins, faecal bile acid degradation and insulin sensitivity that co-varied with specific microbial taxa. CONCLUSION Switching subjects to an MD while maintaining their energy intake reduced their blood cholesterol and caused multiple changes in their microbiome and metabolome that are relevant in future strategies for the improvement of metabolic health.
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Functional interactions between the gut microbiota and host metabolism.
Tremaroli, V, Bäckhed, F
Nature. 2012;489(7415):242-9
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This literature review aims to discuss evidence for the role of the gut microbiota in metabolism and possible links to obesity. Obesity and caloric intake can influence the microbiota, but whether the reverse is true in humans remains unclear. Much of the mechanisms have been determined in rodents, determining similar pathways in humans is difficult. The interplay of diet, host and gut microbiota may cause increased gut permeability (leaky gut) that could lead to an increase in inflammation that may cause obesity, fatty liver disease and insulin resistance. It is increasingly accepted that gut microbiota can contribute to diseases such as obesity, diabetes and cardiovascular disease, but exactly how and by how much remains unclear. Evidence for treating the microbiota to help with these metabolic diseases, either by pre- or probiotic supplementation, is building. However, double-blind, placebo-controlled studies are required to determine effects. The influence of the gut microbiota is a promising area, but one that needs further research.
Abstract
The link between the microbes in the human gut and the development of obesity, cardiovascular disease and metabolic syndromes, such as type 2 diabetes, is becoming clearer. However, because of the complexity of the microbial community, the functional connections are less well understood. Studies in both mice and humans are helping to show what effect the gut microbiota has on host metabolism by improving energy yield from food and modulating dietary or the host-derived compounds that alter host metabolic pathways. Through increased knowledge of the mechanisms involved in the interactions between the microbiota and its host, we will be in a better position to develop treatments for metabolic disease.