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High-fiber diet ameliorates gut microbiota, serum metabolism and emotional mood in type 2 diabetes patients.
Chen, L, Liu, B, Ren, L, Du, H, Fei, C, Qian, C, Li, B, Zhang, R, Liu, H, Li, Z, et al
Frontiers in cellular and infection microbiology. 2023;13:1069954
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Accumulating studies have demonstrated that there are strong correlations between type 2 diabetes mellitus (T2DM) and gut microbiota. A nutritious diet composed of an adequate level of dietary fibres could provide enough carbohydrates for the gut microbiota to ferment, and the microbial metabolites could provide energy supply and regulate the immune function of the host. The aim of this study was to analyse the changes in gut microbiota, serum metabolism and emotional mood of patients with T2DM after consumption of a high-fibre diet. This study was a randomised, open-label, parallel-group clinical trial in T2DM patients with a 4-week treatment period. Seventeen patients clinically diagnosed with T2DM enrolled in the clinical trial and were randomly assigned into two groups: the control group (n = 8) or the intervention group (n = 9). Results showed that the high-fibre diet (compared to the control group): - improved glucose homeostasis and lipid metabolism of participants with T2DM; - decreased serum levels of inflammatory chemokines in participants with T2DM; - alleviated depression and anxiety symptoms, particularly by the uptake of more diverse carbohydrates in the diet in participants with T2DM; - enhanced the diversity of gut microbiota in the treatment group. Authors conclude that the dietary source of fibre demonstrated protective impacts on the gut ecosystem, and the alteration of the gut microbiota composition improved the glucose homeostasis in patients with T2DM.
Abstract
Previous studies have demonstrated that patients with type 2 diabetes mellitus (T2DM) often had the problems of fecal microbiota dysbiosis, and were usually accompanied with psychiatric comorbidities (such as depression and anxiety). Here, we conducted a randomized clinical study to analyze the changes in gut microbiota, serum metabolism and emotional mood of patients with T2DM after consumption of a high-fiber diet. The glucose homeostasis of participants with T2DM was improved by the high-fiber diet, and the serum metabolome, systemic inflammation and psychiatric comorbidities were also altered. The increased abundances of Lactobacillus, Bifidobacterium and Akkermansias revealed that the proportions of beneficial gut microbes were enriched by the high-fiber diet, while the abundances of Desulfovibrio, Klebsiella and other opportunistic pathogens were decreased. Therefore, the current study demonstrated that the intestinal microbiota alterations which were influenced by the high-fiber diet could improve the serum metabolism and emotional mood of patients with T2DM.
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Gut microbiome modulates the effects of a personalised postprandial-targeting (PPT) diet on cardiometabolic markers: a diet intervention in pre-diabetes.
Ben-Yacov, O, Godneva, A, Rein, M, Shilo, S, Lotan-Pompan, M, Weinberger, A, Segal, E
Gut. 2023;72(8):1486-1496
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Diet is a major contributor to cardiometabolic health and plays a fundamental role in the prevention, management and even reversal of many chronic diseases. The gut microbiota has a central role in human health and disease. Specifically, its role in cardiometabolic health has been studied extensively in recent years. The aim of this study was to evaluate the interplay between dietary modifications, microbiome composition and cardiometabolic health outcomes. This study was a randomised controlled trial of a 6-month dietary intervention comparing a personalised postprandial-targeting (PPT) diet versus Mediterranean (MED) diet in 200 adults with pre-diabetes. Results showed that: - PPT intervention induced greater changes in multiple dietary features compared with MED intervention. - PPT intervention increased microbiome diversity and richness and exerted specific microbiome species changes that associate with clinical outcomes. - Changes in specific gut microbiome species partially mediated the effects of dietary modifications on clinical outcomes. Authors conclude that the PPT diet prompted greater changes in gut microbiota composition, consistent with overall greater dietary modifications, as compared with the MED intervention.
Abstract
OBJECTIVE To explore the interplay between dietary modifications, microbiome composition and host metabolic responses in a dietary intervention setting of a personalised postprandial-targeting (PPT) diet versus a Mediterranean (MED) diet in pre-diabetes. DESIGN In a 6-month dietary intervention, adults with pre-diabetes were randomly assigned to follow an MED or PPT diet (based on a machine-learning algorithm for predicting postprandial glucose responses). Data collected at baseline and 6 months from 200 participants who completed the intervention included: dietary data from self-recorded logging using a smartphone application, gut microbiome data from shotgun metagenomics sequencing of faecal samples, and clinical data from continuous glucose monitoring, blood biomarkers and anthropometrics. RESULTS PPT diet induced more prominent changes to the gut microbiome composition, compared with MED diet, consistent with overall greater dietary modifications observed. Particularly, microbiome alpha-diversity increased significantly in PPT (p=0.007) but not in MED arm (p=0.18). Post hoc analysis of changes in multiple dietary features, including food-categories, nutrients and PPT-adherence score across the cohort, demonstrated significant associations between specific dietary changes and species-level changes in microbiome composition. Furthermore, using causal mediation analysis we detect nine microbial species that partially mediate the association between specific dietary changes and clinical outcomes, including three species (from Bacteroidales, Lachnospiraceae, Oscillospirales orders) that mediate the association between PPT-adherence score and clinical outcomes of hemoglobin A1c (HbA1c), high-density lipoprotein cholesterol (HDL-C) and triglycerides. Finally, using machine-learning models trained on dietary changes and baseline clinical data, we predict personalised metabolic responses to dietary modifications and assess features importance for clinical improvement in cardiometabolic markers of blood lipids, glycaemic control and body weight. CONCLUSIONS Our findings support the role of gut microbiome in modulating the effects of dietary modifications on cardiometabolic outcomes, and advance the concept of precision nutrition strategies for reducing comorbidities in pre-diabetes. TRIAL REGISTRATION NUMBER NCT03222791.
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Differential Responders to a Mixed Meal Tolerance Test Associated with Type 2 Diabetes Risk Factors and Gut Microbiota-Data from the MEDGI-Carb Randomized Controlled Trial.
Skantze, V, Hjorth, T, Wallman, M, Brunius, C, Dicksved, J, Pelve, EA, Esberg, A, Vitale, M, Giacco, R, Costabile, G, et al
Nutrients. 2023;15(20)
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Type 2 diabetes (T2D) is a growing worldwide health problem. Increased blood sugars and a corresponding increase in the production of the hormone insulin, which functions to lower blood sugar are risk factors for T2D development. However, it has been shown that everyone has an individual response to the food and the production of differing levels of blood sugar and insulin when eating the same meals has been shown. This secondary analysis of a 12-week randomised control trial of 155 individuals aimed to determine relationships between gut microbiota composition and the glucose response to high and low glycaemic index Mediterranean diets. The results identified two distinct types of response amongst the participants. Cluster A individuals had a lower but more rapid glucose response following food and were deemed to have a better glucose control than cluster B individuals. The clusters also differed in the gut microbiota composition. Cluster A had a higher proportion of Clostridium sensu stricto 1 and a lower proportion of Blautia, than cluster B. It was concluded that the glucose response to a standardised meal can differ between individuals and are associated with differing gut microbiota and risk for T2D. This study could be used by healthcare professionals to understand that diet recommendations are not one size fits all and that the recommendation of certain diets may have differing success. Understanding and differentiating individuals and tailor making recommendations may be of benefit, however further understanding is required on different glucose responses following a meal.
Abstract
The global prevalence of type 2 diabetes mellitus (T2DM) has surged in recent decades, and the identification of differential glycemic responders can aid tailored treatment for the prevention of prediabetes and T2DM. A mixed meal tolerance test (MMTT) based on regular foods offers the potential to uncover differential responders in dynamical postprandial events. We aimed to fit a simple mathematical model on dynamic postprandial glucose data from repeated MMTTs among participants with elevated T2DM risk to identify response clusters and investigate their association with T2DM risk factors and gut microbiota. Data were used from a 12-week multi-center dietary intervention trial involving high-risk T2DM adults, comparing high- versus low-glycemic index foods within a Mediterranean diet context (MEDGICarb). Model-based analysis of MMTTs from 155 participants (81 females and 74 males) revealed two distinct plasma glucose response clusters that were associated with baseline gut microbiota. Cluster A, inversely associated with HbA1c and waist circumference and directly with insulin sensitivity, exhibited a contrasting profile to cluster B. Findings imply that a standardized breakfast MMTT using regular foods could effectively distinguish non-diabetic individuals at varying risk levels for T2DM using a simple mechanistic model.
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Are probiotics, prebiotics, and synbiotics beneficial in primary thyroid diseases? A systematic review with meta-analysis.
Zawadzka, K, Kałuzińska, K, Świerz, MJ, Sawiec, Z, Antonowicz, E, Leończyk-Spórna, M, Abadi, AK, Trofimiuk-Müldner, M, Bała, MM
Annals of agricultural and environmental medicine : AAEM. 2023;30(2):217-223
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Irregularities in intestinal microbial composition are thought to be correlated with thyroid dysfunction. Supplementation of prebiotics, probiotics and synbiotics are gaining momentum in recent times in improving health in general. This systematic review of randomised controlled trials was conducted to summarise the up-to-date evidence on the therapeutic potential of prebiotics, probiotics and synbiotics in the treatment of thyroid disease. The meta-analysis did not show beneficial effects on thyroid hormone balance, BMI or levothyroxine dosage reduction. Supplementation with Lactobacillus and Bifidobacterium resulted in improvement in constipation and a statistically non-significant reduction in thyroid-stimulating hormone in adult participants with hypothyroidism. Further robust long-term studies are required to evaluate the efficacy of prebiotics, probiotics and synbiotics in thyroid disease treatment as the availability of the number of studies included in this systematic review was limited. However, healthcare professionals can use the review to understand the current evidence in this area and the correlation between gut microbial alterations and thyroid disease.
Abstract
INTRODUCTION AND OBJECTIVE A number of studies indicate the presence of a thyroid-gut axis and the important influence of the gut microbiota on thyroid function. As prebiotics, probiotics and synbiotics show therapeutic potential in the treatment of intestinal dysbiosis, the aim of this review is to evaluate the efficacy of their supplementation in primary thyroid diseases. REVIEW METHODS Electronic databases (Ovid MEDLINE, Embase, CENTRAL), registers of clinical trials, and grey literature up to 6 October 2022 were searched for randomised controlled trials (RCTs) meeting pre-specified inclusion criteria. The protocol was registered in PROSPERO (CRD42021235054). BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE After screening 1,721 references, two RCTs were identified, which included 136 hypothyroid participants in total. Meta-analysis of the results after eight weeks of supplementation with predominantly Lactobacillus and Bifidobacterium strains indicated a clinically and statistically nonsignificant decrease in TSH (MD -0.19 mIU/L; 95% CI -0.43 to 0.06; I2= 0%), and no effect on fT3 levels (MD 0.01 pg/mL; 95% CI-0.16 to 0.18; I2= 0%). Data from single studies indicated no significant change in the levels of fT4, thyroid auto-antibodies, BMI, levothyroxine doses, and severity of symptoms measured with validated scales. Only constipation scores showed significant improvement (MD -8.71 points in the Faecal Incontinence Questionnaire; 95% CI -15.85 to -1.57; I2= 0%). SUMMARY Low-certainty evidence from two randomised trials, suggests that routine administration of probiotics, prebiotics or synbiotics may result in little to no benefit in patients with primary hypothyroidism.
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Dynamics of gut microbiota during pregnancy in women with TPOAb-positive subclinical hypothyroidism: a prospective cohort study.
Wu, M, Chi, C, Yang, Y, Guo, S, Li, T, Gu, M, Zhang, T, Gao, H, Liu, R, Yin, C
BMC pregnancy and childbirth. 2022;22(1):592
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Subclinical hypothyroidism (SCH) in pregnancy refers to the elevation of thyroid stimulating hormone level with normal free T4 level. One third of women with SCH have been reported to test positive for anti-thyroid peroxidase antibody (TPOAb+). The aim of this study was to evaluate whether gut microbiota can be potential therapeutic targets for managing TPOAb+ SCH. This study was a nested, prospective observational cohort study. A total of 64 and 68 pregnant women with TPOAb+ and TPOAb negative SCH, respectively, were included in this study. Results showed that women who were diagnosed with TPOAb+ SCH in trimester (T)1 show distinct dynamics of gut microbiota from T2 to T3. Furthermore, changes in the abundances of three types of bacterial species were abnormal in the presence of levothyroxine treatment. Authors conclude that gut microbiota can serve as potential therapeutic targets for TPOAb+ SCH during pregnancy.
Abstract
BACKGROUND Anti-thyroid peroxidase antibody (TPOAb) positivity can contribute to inhibit thyroxine synthesis. Gut microbiota can interact with metabolic or immune diseases. However, dynamics of gut microbiota from the second (T2) to the third trimester (T3) in women with TPOAb-positive/negative subclinical hypothyroidism (TPOAb+/TPOAb- SCH) have not been reported. Therefore, we aimed to evaluate whether gut microbiota can be potential therapeutic targets for managing TPOAb+ SCH. METHODS In this single-center prospective cohort study, we observed gut microbiota dynamics by sequencing 16S rRNA from fecal samples collected in T2 (20-23+ 6 weeks) and T3 (28-33+ 6 weeks). TPOAb+/TPOAb- SCH were stratified depending on whether or not they used levothyroxine (LT4) during the pregnancy (LT4+/LT4-). Microbiome bioinformatics analyses were performed using QIIME2. The linear discriminant analysis effect size (LEfSe) was used for the quantitative analysis of biomarkers. Functional profiling was performed with PICRUSt2. RESULTS Distinct gut microbiota dynamics from T2 to T3 were noted in the TPOAb- (n = 68) and TPOAb+ (n = 64) SCH groups. The TPOAb+ LT4- group was characterized by enriched bacterial amplicon sequence variants (ASVs) of Prevotella in T2 and Bacteria, Lachnospirales, Lachnospiraceae, Blautia, and Agathobacter in T3 and by depleted ASVs of Gammaproteobacteria, Enterobacterales, and Enterobacteriaceae in T2 and Actinobacteriota, Coriobacteriia, Actinobacteria, Coriobacteriales, Bifidobacteriales, Bifidobacteriaceae, Bifidobacterium, Dorea formicigenerans, and Bifidobacterium longum in T3. The TPOAb+ LT4+ group was characterized by enriched bacterial ASVs of Blautia, Streptococcus salivarius, and Bifidobacterium longum in T3 and by depleted ASVs of Bacteroidota, Bacteroidia, Bacteroidales, and Prevotella in T2 and Agathobacter in T3. Moreover, we identified 53 kinds of metabolic functions that were mainly involved in sugar, lipid, and amino acid metabolism. CONCLUSIONS Our results indicated that low dynamics of gut microbiota composition and high dynamics of its metabolic function from T2 to T3 were associated with TPOAb+ SCH. We concluded that gut microbiota could be new targets for treatment of TPOAb+ SCH during pregnancy. TRIAL REGISTRATION This study was retrospectively registered at the Chinese Clinical Trial Registry (registration number ChiCTR2100047175 ) on June 10, 2021.
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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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White common bean extract remodels the gut microbiota and ameliorates type 2 diabetes and its complications: A randomized double-blinded placebo-controlled trial.
Feng, Y, Zhu, J, Wang, Q, Cao, H, He, F, Guan, Y, Li, D, Yan, J, Yang, J, Xia, Y, et al
Frontiers in endocrinology. 2022;13:999715
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Patients with type 2 diabetes (T2D) have a higher risk of macrovascular complications. Intensive glycaemic control reduces microvascular complications and exerts a modest improved effect on macrovascular outcomes. The main aim of this study was to explore the effects of white common bean extract (WCBE) on glucose metabolism and diabetic complications in patients with T2D. This study was a randomised double-blind placebo-controlled trial which enrolled ninety-six patients with T2D aged between 35 and 75 years. Participants were randomly assigned in a 1:2 ratio to the control group and WCBE group. Results showed that WCBE alleviated glucose metabolism dysbiosis and diabetic complication indices. In fact, after 2 months of an intense intervention with a WCBE treatment and in the following two-month maintenance period, the improvements to glycaemic metabolism were preserved. Furthermore, there was notable improvement of the structure of the gut microbiota, especially the enrichment of short-chain fatty acid-producing bacteria and inhibition of opportunistic pathogens. Authors conclude that WCBE may be considered as a novel prebiotic antidiabetic agent for the regulation of glucose metabolism and gut microbiota homeostasis and may slightly ameliorate diabetic complications in patients with T2D.
Abstract
OBJECTIVE Excessive carbohydrate intake is a high risk factor for increased morbidity of type 2 diabetes (T2D). A novel regimen for the dietary care of diabetes that consists of a highly active α-amylase inhibitor derived from white common bean extract (WCBE) and sufficient carbohydrates intake was applied to attenuate T2D and its complications. Furthermore, the role of gut microbiota in this remission was also investigated. METHODS We conducted a 4-month randomized double-blinded placebo-controlled trial. During the intense intervention period, ninety subjects were randomly assigned to the control group (Group C) and WCBE group (Group W). Subjects in Group C were supplemented with 1.5 g of maltodextrin as a placebo. Subjects in Group W took 1.5 g of WCBE half an hour before a meal. Fifty-five participants continued the maintenance intervention receiving the previous dietary intervention whereas less frequent follow-up. The variation in biochemical, vasculopathy and neuropathy indicators and the structure of the fecal microbiota during the intervention was analyzed. RESULT Glucose metabolism and diabetic complications showed superior remission in Group W with a 0.721 ± 0.742% decline of glycosylated hemoglobin after 4 months. The proportion of patients with diabetic peripheral neuropathy (Toronto Clinical Scoring System, TCSS ≥ 6) was significantly lower in Group W than in Group C. Both the left and right sural sensory nerve conduction velocity (SNCV-left sural and SNCV-right sural) slightly decreased in Group C and slightly increased in Group W. Additionally, the abundances of Bifidobacterium, Faecalibacterium and Anaerostipes were higher in Group W, and the abundances of Weissella, Klebsiella, Cronobacter and Enterobacteriaceae_unclassified were lower than those in Group C at month 2. At the end of month 4, Bifidobacterium remained more abundant in Group W. CONCLUSION To our knowledge, this is the first report of improvement to diabetes complications by using a dietary supplement in such a short-term period. The enrichment of SCFA-producing bacteria might be responsible for the attenuation of T2D and its complications. CLINICAL TRIAL REGISTRATION NUMBER http://www.chictr.org.cn/edit.aspx?pid=23309&htm=4, identifier ChiCTR-IOR-17013656.
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Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study).
Zhang, Y, Gu, Y, Ren, H, Wang, S, Zhong, H, Zhao, X, Ma, J, Gu, X, Xue, Y, Huang, S, et al
Nature communications. 2020;11(1):5015
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Berberine, which is a naturally occurring alkaloid found in plants, has been traditionally used as a remedy to protect against Type 2 diabetes and other metabolic disorders. It is important to study how berberine affects the human gut microbiome, specifically in regard to its impact on short-chain fatty acid and bile acid metabolism, due to its low oral bioavailability. The PREMOTE study investigated the glycaemic lowering effects of individual and combination of berberine and probiotics in newly diagnosed Type 2 Diabetes patients. This randomised, double-blinded, placebo-controlled trial included four hundred and nine Type 2 diabetic patients and randomly assigned them (1:1:1:1 ratio) to receive berberine alone, berberine combined with probiotics, probiotics alone or a placebo for twelve weeks. A combination of berberine plus probiotics and berberine alone significantly improved glycated haemoglobin levels compared to the placebo and probiotics alone treatment. The antidiabetic effects of berberine could be due to the Ruminococcus bromii abundance followed by the berberine treatment and its ability to inhibit deoxycholic acid biotransformation. Further robust studies are required to consider the therapeutic application of berberine and probiotics in a general population due to the limitations of the present study. However, healthcare professionals can use the results of this trial to understand the mechanism behind the anti-diabetic effects of berberine and probiotics.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The use of berberine, as a specific antimicrobial agent, along with high strength probiotics may be beneficial for managing blood glucose and potentially other metabolic health markers alongside diet and lifestyle modifications
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Dysbiosis of the human gut microbiome has been associated with the development of type 2 diabetes (T2D). Research has found that, in part, mechanisms of action for the antidiabetic medications, Metformin and Acarbose, include alterations in the gut microbiome as well as the inhibition of bile acid (BA) metabolism and signalling. Remedies targeting the gut microbiota for treatment of T2D and other metabolic diseases have therefore been investigated.
Berberine (BBR) has been used in Indian Ayurvedic and Traditional Chinese Medicine to treat metabolic conditions for hundreds of years. Probiotics have also been extensively researched for their potential metabolic benefits. This randomised, double-blind, placebo-controlled trial aimed to investigate whether BBR and probiotics may be effective in managing T2D.
Methods
A total of 409 participants aged 42-61 years were recruited from 20 medical centres in China. All patients were newly diagnosed (<12 months) with T2D and had no previous antidiabetic medication history. Participants were randomised into 4 groups; Probiotics and BBR, BBR only, probiotics only or a placebo for 12 weeks. Subgroup analysis was also completed for those aged >50 and >54.
Dosage of BBR was 0.6 g prior to a meal, twice daily. 4 g of powdered multi-strain probiotics including 9 strains of lactic acid bacteria were taken at bedtime. All participants were given a 7-day broad-spectrum antibiotic treatment immediately prior to baseline. 391 people completed the trial. The primary outcome measurement was glycaemic haemoglobin (HbA1c). Secondary evaluations of additional metabolic markers included fasting and post-load plasma glucose (FPG, PPG), homeostasis assessment model index for insulin resistance (HOMA-IR), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c) and serum triglycerides (TG).
Results
Results showed a reduction in glycaemic haemoglobin (HbA1c) for both the BBR plus probiotics group (least squares mean [95% CI] -1.04 [-1-19, -0.89]% ) and the BBR only group (-.99 [-1.16, 0.83]%). The results for these groups were significantly greater than the probiotics alone (-0.53 {-068, -0.37]%) and the placebo groups (0.59 [-0.75, -0.44]%).
Secondary metabolic evaluations for FPG and PPG, TC, LDL -c and TGs also showed similar improvements in the BBR and BBR plus probiotic groups only. Additionally, in the >50 and >54 subgroups BBR and probiotics marginally improved the HOMA-IR.
Metagenomic and metabolomic analysis of the gut microbiome was also undertaken after a one-week pre-treatment with antibiotics immediately prior to the trial and at week 13. These results showed that the blood glucose lowering effects of BBR may be due to decreased deoxycholic acid species (DCA) biotransformation by ruminococcus bromii.
Higher levels of adverse gastrointestinal side effects were reported in the BBR treatment groups, however, the authors reported that this did not affect glycemic control outcomes.
Conclusion
This study found that BBR had an antidiabetic effect through microbial alterations in the human gut microbiome
The authors declare no conflicts of interest.
Clinical practice applications:
- 600mg of BBR twice daily prior to a meal plus a multi-strain (lactic acid) probiotic of >50 billion colony forming units (CFU) for 12 weeks may be effective in lowering HbA1c in T2D clients diagnosed within the previous 12 months
- Further research is needed for clients with longer term T2D diagnosis
- Insulin resistance may be marginally improved in clients >50
- Practitioners should be aware that in this study, adverse gastrointestinal side effects were more likely to be be experienced with the use of BBR
Considerations for future research:
The authors reported several limitations to this study:
- A population of Chinese people living in China may not be generalisable to other ethnic/racial populations
- The study was over a short duration. Longer studies are needed to confirm the results
- Participants had newly diagnosed T2D and had not received any previous medications. Future studies should include patients with a longer diagnosis time
- Records should be kept of any additional lifestyle changes made by the participants
- Adverse reactions were experienced in the BBR groups, in this study. It was reported that the gut microbiome and anti-diabetic effects were not affected, however, this may be something to be considered in longer trials.
Abstract
Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], -1.04[-1.19, -0.89]%) and BBR-alone group (-0.99[-1.16, -0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (-0.59[-0.75, -0.44]%, -0.53[-0.68, -0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii. Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261).
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Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial.
Chambers, ES, Byrne, CS, Morrison, DJ, Murphy, KG, Preston, T, Tedford, C, Garcia-Perez, I, Fountana, S, Serrano-Contreras, JI, Holmes, E, et al
Gut. 2019;68(8):1430-1438
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Literature shows that higher intakes of dietary fibre are associated with a reduced risk of type 2 diabetes. The main aim of this study was to elucidate the underlying mechanisms behind improvements in glucose homeostasis following long-term delivery of propionate (a short-chain fatty acid produced by human gut microbiota in response to dietary fibre) to the human colon. The study is a randomised, double-blind, placebo-controlled cross over trial. Fourteen participants randomly received 20 g/day of a low-fermentable fibre control, a high-fermentable fibre control and inulin-propionate ester (IPE) for 42 days each. Results indicate that stool concentrations of short-chain fatty acids were not different following the three supplementation periods. Furthermore, dietary supplementation with 20 g/day IPE promoted no superior impacts on measures of glucose homeostasis compared with inulin (high-fermentable fibre), yet both IPE and inulin improved insulin resistance relative to cellulose (low-fermentable fibre). Authors conclude that manipulating the colonic fermentation profile of a dietary fibre in favour of propionate promotes selective effects on the mechanisms that contribute to metabolic dysregulation.
Abstract
OBJECTIVE To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses. DESIGN Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period. RESULTS Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose. CONCLUSION These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.