scholarly journals Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism

Gut ◽  
2022 ◽  
pp. gutjnl-2021-325753
Author(s):  
Eugeni Belda ◽  
Lise Voland ◽  
Valentina Tremaroli ◽  
Gwen Falony ◽  
Solia Adriouch ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Gut Microbiota ◽  
Severe Obesity ◽  
Human Adipose Tissue ◽  
B Vitamins ◽  
Metabolic State ◽  
Altered Expression ◽  
Registration Number

ObjectivesGut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome’s functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation.DesignWe performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice.ResultsSevere obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration.ConclusionStrategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity.Trial registration numberNCT02059538.

scholarly journals Major microbiota dysbiosis in severe obesity: fate after bariatric surgery

Gut ◽  
2018 ◽  
Vol 68 (1) ◽  
pp. 70-82 ◽  
Author(s):  
Judith Aron-Wisnewsky ◽  
Edi Prifti ◽  
Eugeni Belda ◽  
Farid Ichou ◽  
Brandon D Kayser ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Gut Microbiota ◽  
Severe Obesity ◽  
Shotgun Metagenomics ◽  
Host Interactions ◽  
Registration Number ◽  
Severely Obese ◽  
Obese Subjects ◽  
Gene Richness

ObjectivesDecreased gut microbial gene richness (MGR) and compositional changes are associated with adverse metabolism in overweight or moderate obesity, but lack characterisation in severe obesity. Bariatric surgery (BS) improves metabolism and inflammation in severe obesity and is associated with gut microbiota modifications. Here, we characterised severe obesity-associated dysbiosis (ie, MGR, microbiota composition and functional characteristics) and assessed whether BS would rescue these changes.DesignSixty-one severely obese subjects, candidates for adjustable gastric banding (AGB, n=20) or Roux-en-Y-gastric bypass (RYGB, n=41), were enrolled. Twenty-four subjects were followed at 1, 3 and 12 months post-BS. Gut microbiota and serum metabolome were analysed using shotgun metagenomics and liquid chromatography mass spectrometry (LC-MS). Confirmation groups were included.ResultsLow gene richness (LGC) was present in 75% of patients and correlated with increased trunk-fat mass and comorbidities (type 2 diabetes, hypertension and severity). Seventy-eight metagenomic species were altered with LGC, among which 50% were associated with adverse body composition and metabolic phenotypes. Nine serum metabolites (including glutarate, 3-methoxyphenylacetic acid and L-histidine) and functional modules containing protein families involved in their metabolism were strongly associated with low MGR. BS increased MGR 1 year postsurgery, but most RYGB patients remained with low MGR 1 year post-BS, despite greater metabolic improvement than AGB patients.ConclusionsWe identified major gut microbiota alterations in severe obesity, which include decreased MGR and related functional pathways linked with metabolic deteriorations. The lack of full rescue post-BS calls for additional strategies to improve the gut microbiota ecosystem and microbiome–host interactions in severe obesity.Trial registration numberNCT01454232.

scholarly journals Differences in gut microbiota composition in metabolic syndrome and type 2 diabetes subjects in a multi-ethnic population: the HELIUS study

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Mélanie Deschasaux ◽  
Kristien Bouter ◽  
Andrei Prodan ◽  
Evgeni Levin ◽  
Albert Groen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Gut Microbiota ◽  
Ethnic Groups ◽  
Alpha Diversity ◽  
Microbiota Composition ◽  
Ethnic Population ◽  
Metabolic State ◽  
Gut Microbiota Composition

AbstractRecently, increased attention has been drawn to the composition of the intestinal microbiota and its possible role in metabolic syndrome and type 2 diabetes (T2DM). However, potential variation in gut microbiota composition across ethnic groups is rarely considered despite observed unequal prevalence for these diseases. Our objective was therefore to study the gut microbiota composition across health, metabolic syndrome and T2DM in a multi-ethnic population residing in the same geographical area. 16S rRNA gene sequencing was performed on fecal samples from 3926 participants to the HELIUS cohort (Amsterdam, The Netherlands), representing 6 ethnic groups (Dutch, Ghanaians, Moroccans, Turks, Surinamese of either African or South-Asian descent). Included participants completed a questionnaire and underwent a physical examination and overnight fasted blood sampling. Gut microbiota composition was compared across metabolic status (diabetes with and without metformin use, metabolic syndrome and its subsequent components, health) and ethnicities using Wilcoxon-Mann-Withney tests and logistic regressions. Overall, the gut microbiota alpha-diversity (richness, Shannon index and phylogenetic diversity) decreased with worsening of the metabolic state (comparing health to metabolic syndrome to T2DM) but this was only partially reproduced in ethnic-specific analyses. In line, a lower alpha-diversity was found in relation to all metabolic syndrome components as well as in T2DM subjects using metformin compared to non-users. Alterations, mainly decreased abundances, were also observed at the genus level (many Clostridiales) in metabolic syndrome subjects and more strongly in T2DM subjects with differences across ethnic groups. In particular, we observed decreased abundances of members of the Peptostreptococcaceae family and of Turicibacter and an increased abundance of a member of the Enterobacteriaceae family. Our data highlight several compositional differences in the gut microbiota of individuals with metabolic syndrome or T2DM. These features, confirming prior observations, give some insights into potential key intestinal bacteria related to a worsening of metabolic state. Our results also underscore possible ethnic-specific profiles associated with these microbiota alterations that should be further explored.

Clinical efficacy of bariatric surgery versus liraglutide in patients with type 2 diabetes and severe obesity: a 12-month retrospective evaluation

2014 ◽  
Vol 52 (2) ◽  
pp. 331-336 ◽  
Author(s):  
M. Cotugno ◽  
G. Nosso ◽  
G. Saldalamacchia ◽  
G. Vitagliano ◽  
E. Griffo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Clinical Efficacy ◽  
Severe Obesity ◽  
Retrospective Evaluation

scholarly journals Utilising a milk-based meal replacement programme in a bariatric patient with poorly controlled type 2 diabetes mellitus

2019 ◽  
Vol 2019 ◽  
Author(s):  
Michelle Maher ◽  
Mohammed Faraz Rafey ◽  
Helena Griffin ◽  
Katie Cunningham ◽  
Francis M Finucane
Keyword(s):  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Weight Loss ◽  
Glycaemic Control ◽  
Severe Obesity ◽  
Meal Replacement ◽  
Agonist Therapy ◽  
Severely Obese ◽  
Skimmed Milk

Summary A 45-year-old man with poorly controlled type 2 diabetes (T2DM) (HbA1c 87 mmol/mol) despite 100 units of insulin per day and severe obesity (BMI 40.2 kg/m2) was referred for bariatric intervention. He declined bariatric surgery or GLP1 agonist therapy. Initially, his glycaemic control improved with dietary modification and better adherence to insulin therapy, but he gained weight. We started a low-energy liquid diet, with 2.2 L of semi-skimmed milk (equivalent to 1012 kcal) per day for 8 weeks (along with micronutrient, salt and fibre supplementation) followed by 16 weeks of phased reintroduction of a normal diet. His insulin was stopped within a week of starting this programme, and over 6 months, he lost 20.6 kg and his HbA1c normalised. However, 1 year later, despite further weight loss, his HbA1c deteriorated dramatically, requiring introduction of linagliptin and canagliflozin, with good response. Five years after initial presentation, his BMI remains elevated but improved at 35.5 kg/m2 and his glycaemic control is excellent with a HbA1c of 50 mmol/mol and he is off insulin therapy. Whether semi-skimmed milk is a safe, effective substrate for carefully selected patients with severe obesity complicated by T2DM remains to be determined. Such patients would need frequent monitoring by an experienced multidisciplinary team. Learning points: Meal replacement programmes are an emerging therapeutic strategy to allow severely obese type 2 diabetes patients to achieve clinically impactful weight loss. Using semi-skimmed milk as a meal replacement substrate might be less costly than commercially available programmes, but is likely to require intensive multidisciplinary bariatric clinical follow-up. For severely obese adults with poor diabetes control who decline bariatric surgery or GLP1 agonist therapy, a milk-based meal replacement programme may be an option. Milk-based meal replacement in patients with insulin requiring type 2 diabetes causes rapid and profound reductions in insulin requirements, so rigorous monitoring of glucose levels by patients and their clinicians is necessary. In carefully selected and adequately monitored patients, the response to oral antidiabetic medications may help to differentiate between absolute and relative insulin deficiency.

Altered Expression of Adrenomedullin 2 and its Receptor in the Adipose Tissue of Obese Patients

2019 ◽  
Vol 105 (3) ◽  
pp. e583-e596 ◽  
Author(s):  
Jimin Kim ◽  
Seul Ki Lee ◽  
Donguk Kim ◽  
Han Choe ◽  
Yeon Jin Jang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Receptor Expression ◽  
Receptor Complex ◽  
Obese Patients ◽  
Fat Depots ◽  
Receptor Component

Abstract Context Adrenomedullin 2 (AM2) plays protective roles in the renal and cardiovascular systems. Recent studies in experimental animals demonstrated that AM2 is an adipokine with beneficial effects on energy metabolism. However, there is little information regarding AM2 expression in human adipose tissue. Objective To investigate the pattern and regulation of the expression of AM2 and its receptor component in human adipose tissue, in the context of obesity and type 2 diabetes. Methods We measured metabolic parameters, serum AM2, and expression of ADM2 and its receptor component genes in abdominal subcutaneous and visceral adipose tissue in obese (with or without type 2 diabetes) and normal-weight women. Serum AM2 was assessed before and 6 to 9 months after bariatric surgery. Expression/secretion of AM2 and its receptor were assessed in human adipocytes. Results ADM2 mRNA in both fat depots was higher in obese patients, whether diabetic or not. Although serum AM2 was significantly lower in obese patients, it was not changed after bariatric surgery. AM2 and its receptor complex were predominantly expressed by adipocytes, and the expression of CALCRL, encoding a component of the AM2 receptor complex, was lower in both fat depots of obese patients. Incubating adipocytes with substances mimicking the microenvironment of obese adipose tissue increased ADM2 mRNA but reduced both AM2 secretion into culture media and CALCRL mRNA expression. Conclusions Our data indicate that AM2 signaling is suppressed in adipose tissue in obesity, involving lower receptor expression and ligand availability, likely contributing to insulin resistance and other aspects of the pathophysiology associated with obesity.

scholarly journals In-and-Out Molecular Changes Linked to the Type 2 Diabetes Remission after Bariatric Surgery: An Influence of Gut Microbes on Mitochondria Metabolism

2018 ◽  
Vol 19 (12) ◽  
pp. 3744 ◽  
Author(s):  
Paulina Samczuk ◽  
Hady Hady ◽  
Edyta Adamska-Patruno ◽  
Anna Citko ◽  
Jacek Dadan ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Gut Microbiota ◽  
Diabetes Remission ◽  
Gas Chromatography Mass Spectrometry ◽  
Molecular Changes ◽  
Type 2 Diabetes Remission

Different kinds of gastrointestinal tract modulations known as “bariatric surgery” are actually the most effective treatment for obesity and associated co-morbidities, such as type 2 diabetes (T2DM). The potential causes of those effects have yet to be explained. In our study, we focused on molecular changes evoked by laparoscopic sleeve gastrectomy leading to T2DM remission. Two complementary metabolomics techniques, namely, liquid chromatography coupled with mass spectrometry (LC-MS) and gas chromatography mass spectrometry (GC-MS), were used to study those effects in a group of 20 obese patients with T2DM selected from a cohort of 372 obese individuals who underwent bariatric surgery and did not receive anti-diabetic treatment afterward. Modified levels of carnitines, lipids, amino acids (including BCAA) and α- and β-hydroxybutyric acids were detected. Presented alterations suggest a major role of mitochondria activity in T2DM remission process. Moreover, some of the observed metabolites suggest that changes in gut microbiota composition may also correlate with the tempo of diabetes recovery. Additional analyses confirmed a relationship between biochemical and clinical parameters and the aforementioned metabolites, thereby, highlighting a role of mitochondria and microbes. Our data suggests that there is a previously undescribed relationship between mitochondria and gut microbiota, which changes after the bariatric surgery. More investigations are needed to confirm and explore the observed findings.

scholarly journals Severe obesity in a specialist type 2 diabetes outpatient clinic: an Australian retrospective cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Arunav Thakur ◽  
Dharmesh Sharma ◽  
Bhavya Gupta ◽  
Nikitha Kramadhari ◽  
Rohit Rajagopal ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Severe Obesity ◽  
Sglt2 Inhibitor ◽  
Outpatient Service ◽  
Obesity Management ◽  
Group 13 ◽  
Significant Difference ◽  
Service Referral

Abstract Background Obesity is a major risk factor for the development of type 2 diabetes (T2DM) and its complications. Significant weight loss has been shown to improve glycaemia in people with T2DM and obesity. National and international guidelines recommend considering bariatric surgery for body mass index (BMI) ≥ 35 kg/m2. We assessed the proportion of people with T2DM meeting criteria for surgery, how many had been offered a bariatric/obesity service referral, and compared the characteristics of people with BMI ≥ 35 kg/m2 and BMI < 35 kg/m2. Methods Retrospective data were collected for all people with T2DM aged ≥18 years, attending a hospital specialist diabetes outpatient service over three calendar years, 2017–2019. Results Of 700 people seen in the service, 291 (42%) had BMI ≥ 35 kg/m2 (the “BMI ≥ 35 group”) and met criteria for bariatric surgery, but only 54 (19%) of them were offered referral to an obesity service. The BMI ≥ 35 group was younger than those with a BMI < 35 kg/m2 (56.1 ± 14.8 vs 61.4 ± 14.6 years, p < 0.001) (mean ± SD), with similar diabetes duration (11.0 ± 9.0 vs 12.3 ± 8.9 years, p = 0.078), and there was no significant difference in initial HbA1c (75 ± 27 vs 72 ± 26 mmol/mol, p = 0.118) (9.0 ± 2.5 vs 8.7 ± 2.4%) or proportion treated with insulin (62% vs 58%). There was more GLP1 agonist use in the BMI ≥ 35 group (13% vs 7%, p = 0.003) but similar rates of SGLT2 inhibitor use (25% vs 21%, p = 0.202). The BMI ≥ 35 group received more new medication and/or dose adjustments (74% vs 66%, p = 0.016). Only 29% in the BMI ≥ 35 kg group achieved HbA1c < 53 mmol/mol (7.0%). Conclusions In spite of frequently meeting the criteria for bariatric surgery and not achieving glycaemic targets, people with T2DM in this specialist clinic received limited medical or surgical management of their obesity. This study suggests opportunities for improvement in care of people with T2DM at several levels including increased referrals from T2DM services to weight management/bariatric services, as well as an increased use of GLP1 agonists and SGLT2 inhibitors where appropriate. Our data support the need to prioritise obesity management in the treatment of type 2 diabetes.

scholarly journals Severe Obesity in A Specialist Type 2 Diabetes Outpatient Clinic: An Australian Retrospective Cohort Study

2020 ◽  
Author(s):  
Arunav Thakur ◽  
Dharmesh Sharma ◽  
Bhavya Gupta ◽  
Nikitha Kramadhari ◽  
Rohit Rajagopal ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Severe Obesity ◽  
Sglt2 Inhibitor ◽  
Outpatient Service ◽  
Obesity Management ◽  
Group 13 ◽  
Significant Difference ◽  
Service Referral

Abstract Background Obesity is a major risk factor for the development of type 2 diabetes and its complications. Significant weight loss has been shown to improve glycaemia in people with type 2 diabetes (T2DM) and obesity. National and International guidelines recommend considering bariatric surgery for body mass index (BMI) ≥35 kg/m2. We assessed the proportion of people with T2DM meeting criteria for surgery, how many had been offered a bariatric/obesity service referral, and compared the characteristics of people with BMI≥35kg/m2 and BMI < 35 kg/m2.Methods Retrospective data were collected for all people with T2DM aged ≥18 years, attending a hospital specialist diabetes outpatient service over three calendar years, 2017–2019.Results Of 700 people seen in the service, 291 (42%) had BMI≥35kg/m2 (the “BMI≥35 group”) and met criteria for bariatric surgery, but only 54 (19%) of them were offered referral to an obesity service. The BMI≥35 group was younger than those with a BMI < 35 kg/m2 (56.1 ± 14.8 vs 61.4 ± 14.6 years, p < 0.001) (mean ± SD), with similar diabetes duration (11.0 ± 9.0 vs 12.3 ± 8.9 years, p = 0.078), and there was no significant difference in initial HbA1c (75 ± 27 vs 72 ± 26 mmol/mol, p = 0.118) (9.0 ± 2.5 vs 8.7 ± 2.4%) or proportion treated with insulin (62% vs 58%). There was more GLP1 agonist use in the BMI≥35 group (13% vs 7%, p = 0.003) but similar rates of SGLT2 inhibitor use (25% vs 21%, p = 0.202). The BMI≥35 group received more new medication and/or dose adjustments (74% vs 66%, p = 0.016). Only 29% in the BMI≥35kg group achieved HbA1c < 53 mmol/mol (7.0%).Conclusions In spite of frequently meeting the criteria for bariatric surgery and not achieving glycaemic targets, people with T2DM in this specialist clinic received limited medical or surgical management of their obesity. Our data support the need to prioritise obesity management in the treatment of type 2 diabetes.

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