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Serum, Urine, and Fecal Metabolome Alterations in the Gut Microbiota in Response to Lifestyle Interventions in Pediatric Obesity: A Non-Randomized Clinical Trial.
Lee, Y, Cho, JY, Cho, KY
Nutrients. 2023;15(9)
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Paediatric obesity is linked to an increased risk of type 2 diabetes, hypertension, dyslipidaemia, and metabolic syndrome. Diverse evidence suggests that obesity is associated with alterations in the gut microbiota and its metabolites. The aim of this study was to understand the metabolic pathways underlying paediatric obesity and the effect of intervention, which could provide guidance for the treatment of obesity. This study was a non-randomised clinical trial which enrolled 50 children with obesity and 22 normal-weight children aged 7–18 years. Results showed that imbalances in microbiota and metabolites were associated with both obesity and response to the intervention. The most distinct metabolic alterations in the obese group were branched-chain amino acid and purine changes. Authors conclude that the findings of their study could be valuable for identifying novel targets and biomarkers for the treatment of obesity.
Abstract
Pediatric obesity is associated with alterations in the gut microbiota and its metabolites. However, how they influence obesity and the effect of lifestyle interventions remains unknown.. In this non-randomized clinical trial, we analyzed metabolomes and microbial features to understand the associated metabolic pathways and the effect of lifestyle interventions on pediatric obesity. Anthropometric/biochemical data and fasting serum, urine, and fecal samples were collected at baseline and after an eight-week, weight-reduction lifestyle modification program. Post-intervention, children with obesity were classified into responder and non-responder groups based on changes in total body fat. At baseline, serum L-isoleucine and uric acid levels were significantly higher in children with obesity compared with those in normal-weight children and were positively correlated with obesogenic genera. Taurodeoxycholic and tauromuricholic α + β acid levels decreased significantly with obesity and were negatively correlated with obesogenic genera. Branched-chain amino acid and purine metabolisms were distinguished metabolic pathways in the obese group. Post-intervention, urinary myristic acid levels decreased significantly in the responder group, showing a significant positive correlation with Bacteroides. Fatty acid biosynthesis decreased significantly in the responder group. Thus, lifestyle intervention with weight loss is associated with changes in fatty acid biosynthesis, and myristic acid is a possible therapeutic target for pediatric obesity.
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Impact of dietary interventions on pre-diabetic oral and gut microbiome, metabolites and cytokines.
Shoer, S, Shilo, S, Godneva, A, Ben-Yacov, O, Rein, M, Wolf, BC, Lotan-Pompan, M, Bar, N, Weiss, EI, Houri-Haddad, Y, et al
Nature communications. 2023;14(1):5384
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Pre-diabetes, a condition characterized by elevated blood glucose levels but below diabetes thresholds, is a significant risk factor for the development of type 2 diabetes, as well as other comorbidities including cardiovascular and kidney diseases. Diet plays a critical role in the development of hyperglycaemia and the onset of pre-diabetes. The aim of this study was to assess the impact of a personalized postprandial glucose-targeting diet (PPT), as well as the standard of care Mediterranean diet (MED), on the oral and gut microbiome, metabolites and cytokines in 200 pre-diabetic individuals. This study was a biphasic, randomised, controlled, single-blind dietary intervention. Phase one included a six-month intervention that compared two diets targeting glycaemic control, while phase two included a six-month follow-up period. Participants (n = 225) were randomly assigned in a 1:1 ratio to a PPT (n = 113) or a MED (n = 112). Results showed that participants assigned to the PPT diet had significant changes in 19 gut microbial species, 14 gut and one oral microbial pathway, 86 serum metabolites and four cytokines. Participants assigned to the MED diet showed significant changes in five gut and one oral microbial species, 18 gut microbial pathways, 27 serum metabolites and four cytokines. Authors conclude that dietary interventions can affect the microbiome, cardiometabolic profile and immune response of the host. Thus, diets such as the PPT used in this study, which takes into account microbiome features, could be designed to affect the microbiome and inflict desired metabolic outcomes.
Abstract
Diabetes and associated comorbidities are a global health threat on the rise. We conducted a six-month dietary intervention in pre-diabetic individuals (NCT03222791), to mitigate the hyperglycemia and enhance metabolic health. The current work explores early diabetes markers in the 200 individuals who completed the trial. We find 166 of 2,803 measured features, including oral and gut microbial species and pathways, serum metabolites and cytokines, show significant change in response to a personalized postprandial glucose-targeting diet or the standard of care Mediterranean diet. These changes include established markers of hyperglycemia as well as novel features that can now be investigated as potential therapeutic targets. Our results indicate the microbiome mediates the effect of diet on glycemic, metabolic and immune measurements, with gut microbiome compositional change explaining 12.25% of serum metabolites variance. Although the gut microbiome displays greater compositional changes compared to the oral microbiome, the oral microbiome demonstrates more changes at the genetic level, with trends dependent on environmental richness and species prevalence in the population. In conclusion, our study shows dietary interventions can affect the microbiome, cardiometabolic profile and immune response of the host, and that these factors are well associated with each other, and can be harnessed for new therapeutic modalities.
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Gut microbiota in nonalcoholic fatty liver disease: a PREDIMED-Plus trial sub analysis.
Gómez-Pérez, AM, Ruiz-Limón, P, Salas-Salvadó, J, Vioque, J, Corella, D, Fitó, M, Vidal, J, Atzeni, A, Torres-Collado, L, Álvarez-Sala, A, et al
Gut microbes. 2023;15(1):2223339
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Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease. The aim of this study was to evaluate the changes in the microbiota associated with changes in biochemical markers of NAFLD/NASH after an intervention. This substudy was conducted in the frame of the PREDIMED-Plus study, a 6-year, multicentre, randomised clinical trial for primary prevention of cardiovascular disease (CVD) conducted in men aged 55–75 years and women aged 60–75 years with overweight or obesity and metabolic syndrome. Results showed a relationship between liver disease biochemical indexes changes and gut microbiota changes within a context of a Mediterranean lifestyle. In fact, two noninvasive scores for liver steatosis and liver fibrosis, usually used in clinical practice, could differentiate gut microbiota populations. Authors conclude that their findings highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations.
Abstract
To evaluate the changes in the gut microbiota associated with changes in the biochemical markers of nonalcoholic fatty liver disease (NAFLD) after a lifestyle intervention with the Mediterranean diet. Participants (n = 297) from two centers of PREDIMED-Plus trial (Prevención con Dieta Mediterránea) were divided into three different groups based on the change tertile in the Hepatic Steatosis Index (HSI) or the Fibrosis-4 score (FIB-4) between baseline and one year of intervention. One-year changes in HSI were: tertile 1 (T1) (-24.9 to -7.51), T2 (-7.5 to -1.86), T3 (-1.85 to 13.64). The most significant differences in gut microbiota within the year of intervention were observed in the T1 and T3. According to the FIB-4, participants were categorized in non-suspected fibrosis (NSF) and with indeterminate or suspected fibrosis (SF). NSF participants showed higher abundances of Alcaligenaceae, Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Peptostreptococcaceae, Verrucomicrobiaceae compared to those with SF. Then, participants were divided depending on the FIB-4 tertile of change: T1 (-89.60 to -5.57), T2 (-5.56 to 11.4), and T3 (11.41 to 206.24). FIB-4 T1 showed a decrease in Akkermansia and an increase in Desulfovibrio. T2 had an increase in Victivallaceae, Clostridiaceae, and Desulfovibrio. T3 showed a decrease in Enterobacteriaceae, and an increase in Sutterella, Faecalibacterium, and Blautia. A relation between biochemical index changes of NAFLD/NASH (HSI and FIB-4) and gut microbiota changes were found. These observations highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations. What You Need to KnowWhat is the context:Obesity and metabolic syndrome have been associated with nonalcoholic fatty liver disease (NAFLD). Gut microbiota and its interaction with the environment may play a key role in NAFLD.What is new:Mediterranean diet and physical activity can modify the scores for liver steatosis (HSI) and liver fibrosis (FIB−4) in only one year. A relation between the changes in these scores and gut microbiota changes was found.What is the impact:The discovery of microbiota-based biomarkers for NAFLD and the development of strategies to modulate gut microbiota in the treatment of NAFLD.
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Probio-X Relieves Symptoms of Hyperlipidemia by Regulating Patients' Gut Microbiome, Blood Lipid Metabolism, and Lifestyle Habits.
Wang, H, Ma, C, Li, Y, Zhang, L, A, L, Yang, C, Zhao, F, Han, H, Shang, D, Yang, F, et al
Microbiology spectrum. 2023;11(3):e0444022
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A long-term high-fat diet will not only disrupt the balance of lipid metabolism in the body and cause metabolic disorders but also lead to chronic diseases, such as hyperlipidaemia, type 2 diabetes, hypertension, and obesity. Hyperlipidaemia is also an important contributing factor in cardiovascular disease. The aim of this study was to analyse the effects of a mixed probiotic formulation on hyperlipidaemia, with focus on changes in patients’ gut microbiota and their metabolic potential. This study was a 3-month randomised controlled intervention trial. A total of 56 hyperlipidaemic patients were recruited and randomised into either the placebo or probiotic (receiving a mixed probiotic formulation) group. Results show that the intake of the probiotic mix effectively reduced the serum levels of total cholesterol and low-density lipoprotein cholesterol, while increasing serum high-density lipoprotein cholesterol levels, in patients with hyperlipidaemia. In fact, there was a strong association between the desirable changes in patients’ lifestyle habits and lowering of these indexes. Furthermore, although insignificant changes were observed in the lipid metabolome and gut microbiota structure, some interesting fecal bacteria and blood metabolites increased significantly after Probio-X intervention. Authors conclude that their findings show that probiotic administration is a promising approach in managing hyperlipidaemia and improving public health.
Abstract
Hyperlipidemia is a key risk factor for cardiovascular disease, and it is associated with lipid metabolic disorders and gut microbiota dysbiosis. Here, we aimed to investigate the beneficial effects of 3-month intake of a mixed probiotic formulation in hyperlipidemic patients (n = 27 and 29 in placebo and probiotic groups, respectively). The blood lipid indexes, lipid metabolome, and fecal microbiome before and after the intervention were monitored. Our results showed that probiotic intervention could significantly decrease the serum levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol (P < 0.05), while increasing the levels of high-density lipoprotein cholesterol (P < 0.05) in patients with hyperlipidemia. Probiotic recipients showing improved blood lipid profile also exhibited significant differences in their lifestyle habits after the 3-month intervention, with an increase in daily intake of vegetable and dairy products, as well as weekly exercise time (P < 0.05). Moreover, two blood lipid metabolites (namely, acetyl-carnitine and free carnitine) significantly increased after probiotic supplementation cholesterol (P < 0.05). In addition, probiotic-driven mitigation of hyperlipidemic symptoms were accompanied by increases in beneficial bacteria like Bifidobacterium animalis subsp. lactis and Lactiplantibacillus plantarum in patients' fecal microbiota. These results supported that mixed probiotic application could regulate host gut microbiota balance, lipid metabolism, and lifestyle habits, through which hyperlipidemic symptoms could be alleviated. The findings of this study urge further research and development of probiotics into nutraceuticals for managing hyperlipidemia. IMPORTANCE The human gut microbiota have a potential effect on the lipid metabolism and are closely related to the disease hyperlipidemia. Our trial has demonstrated that 3-month intake of a mixed probiotic formulation alleviates hyperlipidemic symptoms, possibly by modulation of gut microbes and host lipid metabolism. The findings of the present study provide new insights into the treatment of hyperlipidemia, mechanisms of novel therapeutic strategies, and application of probiotics-based therapy.
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An insight into the functional alterations in the gut microbiome of healthy adults in response to a multi-strain probiotic intake: a single arm open label trial.
Rodenes-Gavidia, A, Lamelas, A, Bloor, S, Hobson, A, Treadway, S, Haworth, J, Vijayakumar, V, Naghibi, M, Day, R, Chenoll, E
Frontiers in cellular and infection microbiology. 2023;13:1240267
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The human gut microbiota is a key mediator of host health and is known to affect many physiological processes, such as digestion, metabolism, immune function and inhibition of pathogen colonisation. The gut microbiome can be impacted by many extrinsic factors. The aim of this study was to assess both compositional and functional changes in the microbiome of healthy individuals using shotgun metagenomics following 8-weeks of daily multi-strain probiotic intake. This study was a single-arm open-label study which enrolled a total of 41 healthy adult males and females between 18 to 40 years old. Results showed that alpha- and beta-diversity of the faecal microbiota structure was not significantly altered in response to probiotic intake. However, significant changes were observed when functional genes were assessed. Abundance of certain genes involved in several functional pathways were also significantly altered. Additionally, there were no significant changes in stool frequency or consistency, faecal biochemistry, or breath tests of methane and hydrogen observed. Authors conclude that the findings of their study have the potential to provide insights into the underlying mechanisms of action of the 14-strain probiotic blend in healthy adults.
Abstract
BACKGROUND Probiotic supplements, by definition, provide a benefit to the host, but few studies have investigated the effect of probiotic supplements in healthy adult populations. PURPOSE The present, single arm, open label clinical trial, evaluated compositional and functional changes in the fecal microbiome of healthy adults after supplementation with a 14-strain probiotic. METHODS We analysed the effect of a 14-strain probiotic blend (Bacillus subtilis NCIMB 30223, Bifidobacterium bifidum NCIMB 30179, B. breve NCIMB 30180, B. infantis NCIMB 30181, B. longum NCIMB 30182, Lactobacillus helveticus NCIMB 30184, L. delbrueckii subsp. bulgaricus NCIMB 30186, Lacticaseibacillus paracasei NCIMB 30185, Lactiplantibacillus plantarum NCIMB 30187, Lacticaseibacillus rhamnosus NCIMB 30188, L. helveticus NCIMB 30224, Lactobacillus salivarius NCIMB 30225, Lactococcus lactis subsp. lactis NCIMB 30222, and Streptococcus thermophilus NCIMB 30189), on the faecal microbiota of healthy young adults (n=41) in a single arm study. The adults consumed 4 capsules daily of the 14 strain blend(8 billion colony forming units/day) for 8 weeks. Compositional and functional changes in faecal microbiota before and after supplementation were assessed using shotgun metagenomic sequencing. Fasting breath analysis, faecal biochemistry and bowel habits were also assessed. RESULTS In healthy adult participants, no significant changes to the overall alpha- or beta-diversity was observed after 8 weeks of multi-strain probiotic supplementation. However, in a simplified model that considered only time and individual differences, significant decreases (p < 0.05) in family Odoribacteraceae and Bacteroidaceae abundance and a significant increase (p < 0.05) in genus Megamonas abundance were observed. At a functional level, there were significant changes in functional gene abundance related to several functional pathways, including phenylalanine metabolism, O-antigen nucleotide sugar biosynthesis, bacterial chemotaxis, and flagellar assembly. No significant changes in stool form or frequency, fecal biochemistry, or methane and hydrogen breath tests were observed. CONCLUSION In healthy young adults, overall alpha- and beta-diversity did not change in response to probiotic intake even though modest compositional changes at the family and genus level were observed. However, at functional level, results identified changes in gene abundance for several functional pathways.
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Time-restricted feeding's effect on overweight and obese patients with chronic kidney disease stages 3-4: A prospective non-randomized control pilot study.
Lao, BN, Luo, JH, Xu, XY, Fu, LZ, Tang, F, Ouyang, WW, Xu, XZ, Wei, MT, Xiao, BJ, Chen, LY, et al
Frontiers in endocrinology. 2023;14:1096093
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Obesity is a chronic metabolic disease caused by multiple factors. It is an independent risk factor for the development and progression of chronic kidney disease (CKD). The aim of this study was to explore the efficacy and safety of TRF in overweight and obese patients with moderate-to-severe stage CKD. This study was a prospective, non-randomised, controlled exploratory intervention study. Twenty-eight participants were included in the study, and were assigned to either the time-restricted feeding (TRF) group or the control diet (CD) group according to their preferences. Results showed that: - TRF helped improve renal function in overweight and obese moderate-to-severe CKD patients. - the TRF group experienced some hunger, but within tolerable range, and stated that TRF adherence was good. - the TRF group experienced a decrease in serum phosphate and uric acid, maintenance of total protein and albumin. - TRF shifted the gut microbiota in a positive direction. Authors concluded that TRF may be a safe and effective dietary intervention for overweight and obese CKD patients.
Abstract
BACKGROUND Time-restricted feeding (TRF) has become a popular weight loss method in recent years. It is widely used in the nutritional treatment of normal obese people and obese people with chronic diseases such as diabetes mellitus and hypertension, and has shown many benefits. However, most TRF studies have excluded chronic kidney disease (CKD) patients, resulting in a lack of sufficient evidence-based practice for the efficacy and safety of TRF therapy for CKD. Therefore, we explore the efficacy and safety of TRF in overweight and obese patients with moderate-to-severe stage CKD through this pilot study, and observe patient compliance to assess the feasibility of the therapy. METHODS This is a prospective, non-randomized controlled short-term clinical trial. We recruited overweight and obese patients with CKD stages 3-4 from an outpatient clinic and assigned them to either a TRF group or a control diet (CD) group according to their preferences. Changes in renal function, other biochemical data, anthropometric parameters, gut microbiota, and adverse events were measured before the intervention and after 12 weeks. RESULTS The change in estimated glomerular filtration rate (eGFR) before and after intervention in the TRF group (Δ = 3.1 ± 5.3 ml/min/1.73m2) showed significant improvement compared with the CD group (Δ = -0.8 ± 4.4 ml/min/1.73m2). Furthermore, the TRF group had a significant decrease in uric acid (Δ = -70.8 ± 124.2 μmol/L), but an increase in total protein (Δ = 1.7 ± 2.5 g/L), while the changes were inconsistent for inflammatory factors. In addition, the TRF group showed a significant decrease in body weight (Δ = -2.8 ± 2.9 kg) compared to the CD group, and body composition indicated the same decrease in body fat mass, fat free mass and body water. Additionally, TRF shifted the gut microbiota in a positive direction. CONCLUSION Preliminary studies suggest that overweight and obese patients with moderate-to-severe CKD with weight loss needs, and who were under strict medical supervision by healthcare professionals, performed TRF with good compliance. They did so without apparent adverse events, and showed efficacy in protecting renal function. These results may be due to changes in body composition and alterations in gut microbiota.
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Exploring choices of early nutritional support for patients with sepsis based on changes in intestinal microecology.
Yang, XJ, Wang, XH, Yang, MY, Ren, HY, Chen, H, Zhang, XY, Liu, QF, Yang, G, Yang, Y, Yang, XJ
World journal of gastroenterology. 2023;29(13):2034-2049
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Sepsis is a condition brought about by infection and results in organ dysfunction and gut microbiota imbalance. Nutrition plays a large part in recovery from sepsis, however it is unclear as to the optimal diet for gut microbial balance in individuals with sepsis. This randomised control trial of 30 individuals with sepsis aimed to determine the optimal delivery of nutrition for gut microbial health either through a gastric tube (TEN), through the jugular vein (TPN), or a mixture of the two modes (SPN). The results showed differences in gut microbiota composition between the different modes of nutrition. Enterococcus increased in TEN, Campylobacter decreased in TPN, and Dialister decreased in SPN groups. Fermentation products produced by gut microbiota also changed depending on the mode of nutrition, with the TEN group showing improvements amongst the most fermentation products. Individuals in the TEN group also showed improved immune system function alongside those in the SPN group. It was concluded that based upon improvements to the immune system and gut microbiota, TEN is the most suitable mode for nutrition in individuals with sepsis. This study could be used by healthcare professionals to understand that nutrition methods for individuals with sepsis aren’t equally effective and recovery may be faster if individuals receive nutrition through a gastric tube.
Abstract
BACKGROUND Sepsis exacerbates intestinal microecological disorders leading to poor prognosis. Proper modalities of nutritional support can improve nutrition, immunity, and intestinal microecology. AIM: To identify the optimal modality of early nutritional support for patients with sepsis from the perspective of intestinal microecology. METHODS Thirty patients with sepsis admitted to the intensive care unit of the General Hospital of Ningxia Medical University, China, between 2019 and 2021 with indications for nutritional support, were randomly assigned to one of three different modalities of nutritional support for a total of 5 d: Total enteral nutrition (TEN group), total parenteral nutrition (TPN group), and supplemental parenteral nutrition (SPN group). Blood and stool specimens were collected before and after nutritional support, and changes in gut microbiota, short-chain fatty acids (SCFAs), and immune and nutritional indicators were detected and compared among the three groups. RESULTS In comparison with before nutritional support, the three groups after nutritional support presented: (1) Differences in the gut bacteria (Enterococcus increased in the TEN group, Campylobacter decreased in the TPN group, and Dialister decreased in the SPN group; all P < 0.05); (2) different trends in SCFAs (the TEN group showed improvement except for Caproic acid, the TPN group showed improvement only for acetic and propionic acid, and the SPN group showed a decreasing trend); (3) significant improvement of the nutritional and immunological indicators in the TEN and SPN groups, while only immunoglobulin G improved in the TPN group (all P < 0.05); and (4) a significant correlation was found between the gut bacteria, SCFAs, and nutritional and immunological indicators (all P < 0.05). CONCLUSION TEN is recommended as the preferred mode of early nutritional support in sepsis based on clinical nutritional and immunological indicators, as well as changes in intestinal microecology.
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An open label, non-randomized study assessing a prebiotic fiber intervention in a small cohort of Parkinson's disease participants.
Hall, DA, Voigt, RM, Cantu-Jungles, TM, Hamaker, B, Engen, PA, Shaikh, M, Raeisi, S, Green, SJ, Naqib, A, Forsyth, CB, et al
Nature communications. 2023;14(1):926
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Risk determinants for Parkinson’s disease (PD) include both genetic and environmental factors. Whether sporadic or monogenetic in origin, environmental factors may be critical in triggering PD onset in a susceptible host or influencing disease progression. The aims of this study were to determine whether prebiotic fibres can increase short-chain fatty acids (SCFA) production in PD patient microbiota and (2) determine which prebiotics modify the microbiota and increase SCFA using a stool fermentation system. Results showed that 10 days of prebiotic intervention was both well-tolerated and safe in PD patients and decreased total gastrointestinal symptom severity score in treated PD participants. The prebiotic intervention was also associated with anti-inflammatory shifts in the intestinal microbiota, increased SCFA, reduced calprotectin (intestinal inflammation), reduced zonulin (a putative marker of intestinal barrier dysfunction/ inflammation), and a subtle, but statistically significant, reduction in neurofilament light (a marker of neurodegeneration). Authors concluded that a SCFA-promoting prebiotic fibre mixture can be used to modulate the intestinal microbiota in PD patients (i.e., the approach is feasible) and that the prebiotic mixture is well-accepted, tolerated, and safe for use in PD patients.
Abstract
A pro-inflammatory intestinal microbiome is characteristic of Parkinson's disease (PD). Prebiotic fibers change the microbiome and this study sought to understand the utility of prebiotic fibers for use in PD patients. The first experiments demonstrate that fermentation of PD patient stool with prebiotic fibers increased the production of beneficial metabolites (short chain fatty acids, SCFA) and changed the microbiota demonstrating the capacity of PD microbiota to respond favorably to prebiotics. Subsequently, an open-label, non-randomized study was conducted in newly diagnosed, non-medicated (n = 10) and treated PD participants (n = 10) wherein the impact of 10 days of prebiotic intervention was evaluated. Outcomes demonstrate that the prebiotic intervention was well tolerated (primary outcome) and safe (secondary outcome) in PD participants and was associated with beneficial biological changes in the microbiota, SCFA, inflammation, and neurofilament light chain. Exploratory analyses indicate effects on clinically relevant outcomes. This proof-of-concept study offers the scientific rationale for placebo-controlled trials using prebiotic fibers in PD patients. ClinicalTrials.gov Identifier: NCT04512599.
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Fecal microbiota composition is related to brown adipose tissue 18F-fluorodeoxyglucose uptake in young adults.
Ortiz-Alvarez, L, Acosta, FM, Xu, H, Sanchez-Delgado, G, Vilchez-Vargas, R, Link, A, Plaza-Díaz, J, Llamas, JM, Gil, A, Labayen, I, et al
Journal of endocrinological investigation. 2023;46(3):567-576
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Brown adipose tissue (BAT) is a tissue that dissipates energy through the action of the uncoupling protein-1. Moreover, BAT takes up and oxidises glucose and lipids, as such working as a nutrient sink, and through its endocrine function may have cardiometabolic benefits. The aim of this study was to investigate the association of fecal microbiota composition with BAT volume and activity in young adults. This study was a cross-sectional study of 92 young healthy adults (27 men and 65 women, age: 18–25 years old). Results showed that the relative abundance of: - specific genera (Akkermansia, Lachnospiraceae sp., and Ruminococcus) were negatively correlated with BAT volume and activity. - Bifdobacterium genus was positively correlated with BAT activity. Authors concluded faecal microbiota is involved in the regulation of glucose uptake by human BAT and other metabolic tissues including white adipose tissue and skeletal muscles in young adults.
Abstract
OBJECTIVE Human brown adipose tissue (BAT) has gained considerable attention as a potential therapeutic target for obesity and its related cardiometabolic diseases; however, whether the gut microbiota might be an efficient stimulus to activate BAT metabolism remains to be ascertained. We aimed to investigate the association of fecal microbiota composition with BAT volume and activity and mean radiodensity in young adults. METHODS 82 young adults (58 women, 21.8 ± 2.2 years old) participated in this cross-sectional study. DNA was extracted from fecal samples and 16S rRNA sequencing was performed to analyse the fecal microbiota composition. BAT was determined via a static 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography scan (PET/CT) after a 2 h personalized cooling protocol. 18F-FDG uptake was also quantified in white adipose tissue (WAT) and skeletal muscles. RESULTS The relative abundance of Akkermansia, Lachnospiraceae sp. and Ruminococcus genera was negatively correlated with BAT volume, BAT SUVmean and BAT SUVpeak (all rho ≤ - 0.232, P ≤ 0.027), whereas the relative abundance of Bifidobacterium genus was positively correlated with BAT SUVmean and BAT SUVpeak (all rho ≥ 0.262, P ≤ 0.012). On the other hand, the relative abundance of Sutterellaceae and Bifidobacteriaceae families was positively correlated with 18F-FDG uptake by WAT and skeletal muscles (all rho ≥ 0.213, P ≤ 0.042). All the analyses were adjusted for the PET/CT scan date as a proxy of seasonality. CONCLUSION Our results suggest that fecal microbiota composition is involved in the regulation of BAT and glucose uptake by other tissues in young adults. Further studies are needed to confirm these findings. CLINICAL TRIAL INFORMATION ClinicalTrials.gov no. NCT02365129 (registered 18 February 2015).
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A structured weight loss program increases gut microbiota phylogenetic diversity and reduces levels of Collinsella in obese type 2 diabetics: A pilot study.
Frost, F, Storck, LJ, Kacprowski, T, Gärtner, S, Rühlemann, M, Bang, C, Franke, A, Völker, U, Aghdassi, AA, Steveling, A, et al
PloS one. 2019;14(7):e0219489
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The global obesity epidemic is a major cause of the increase in type 2 diabetes mellitus (T2DM) and ensuing cardiovascular disease. The causes of obesity are complex ,and it has been shown that changes in the microbiome are associated with obesity. The microbiome can be altered through dietary intervention and weight loss. The aim of this open label pilot study was to investigate the microbiome of obese patients with T2DM during a weight loss programme. During the first six weeks the diet consisted of formula drink providing 800kcal per day, followed by nine weeks during which a regular diet of 1,200-1,500kcal per day was reintroduced, depending on the individuals’ needs. All participants lost weight continuously over the 15 weeks, from an average BMI of 39.6 at the start to 33.1 at the end of the programme. This was accompanied with an improvement in glucose metabolism, total and LDL cholesterol and uric acid levels, but not HDL cholesterol or triglycerides. All participants experienced changes in their microbiome towards greater diversity after the first six weeks of the low-calorie formula diet but these changes were partially reversed at the end of the study period at 15 weeks. A particular type of bacteria, Collinsella, which has been associated with poor metabolic health, was the only type found to remain reduced at the end of the 15 weeks, an 8.4-fold decrease. The authors hypothesise that this reduction in Collinsella may be associated with the improvement of metabolic factor in these patients at the end of the study.
Abstract
The global obesity epidemic constitutes a major cause of morbidity and mortality challenging public health care systems worldwide. Thus, a better understanding of its pathophysiology and the development of novel therapeutic options are urgently needed. Recently, alterations of the intestinal microbiome in the obese have been discussed as a promoting factor in the pathophysiology of obesity and as a contributing factor to related diseases such as type 2 diabetes and metabolic syndrome. The present pilot study investigated the effect of a structured weight loss program on fecal microbiota in obese type 2 diabetics. Twelve study subjects received a low-calorie formula diet for six weeks, followed by a nine week food reintroduction and stabilization period. Fecal microbiota were determined by 16S rRNA gene sequencing of stool samples at baseline, after six weeks and at the end of the study after fifteen weeks. All study subjects lost weight continuously throughout the program. Changes in fecal microbiota were most pronounced after six weeks of low-calorie formula diet, but reverted partially until the end of the study. However, the gut microbiota phylogenetic diversity increased persistently. The abundance of Collinsella, which has previously been associated with atherosclerosis, decreased significantly during the weight loss program. This study underlines the impact of dietary changes on the intestinal microbiome and further demonstrates the beneficial effects of weight loss on gut microbiota. Trial registration: ClinicalTrials.gov NCT02970838.