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Microbial-derived imidazole propionate links the heart failure-associated microbiome alterations to disease severity.
Raju, SC, Molinaro, A, Awoyemi, A, Jørgensen, SF, Braadland, PR, Nendl, A, Seljeflot, I, Ueland, PM, McCann, A, Aukrust, P, et al
Genome medicine. 2024;(1):27
Abstract
BACKGROUND Interactions between the gut microbiota, diet, and host metabolism contribute to the development of cardiovascular disease, but a firm link between disease-specific gut microbiota alterations and circulating metabolites is lacking. METHODS We performed shot-gun sequencing on 235 samples from 166 HF patients and 69 healthy control samples. Separate plasma samples from healthy controls (n = 53) were used for the comparison of imidazole propionate (ImP) levels. Taxonomy and functional pathways for shotgun sequencing data was assigned using MetaPhlAn3 and HUMAnN3 pipelines. RESULTS Here, we show that heart failure (HF) is associated with a specific compositional and functional shift of the gut microbiota that is linked to circulating levels of the microbial histidine-derived metabolite ImP. Circulating ImP levels are elevated in chronic HF patients compared to controls and associated with HF-related gut microbiota alterations. Contrary to the microbiota composition, ImP levels provide insight into etiology and severity of HF and also associate with markers of intestinal permeability and systemic inflammation. CONCLUSIONS Our findings establish a connection between changes in the gut microbiota, the presence, etiology, and severity of HF, and the gut-microbially produced metabolite ImP. While ImP appears promising as a circulating biomarker reflecting gut dysbiosis related to HF, further studies are essential to demonstrate its causal or contributing role in HF pathogenesis. TRIAL REGISTRATION NCT02637167, registered December 22, 2015.
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Age-dependent changes in the gut microbiota and serum metabolome correlate with renal function and human aging.
Sun, L, Li, Z, Hu, C, Ding, J, Zhou, Q, Pang, G, Wu, Z, Yang, R, Li, S, Li, J, et al
Aging cell. 2023;(12):e14028
Abstract
Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age-dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age-dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota-metabolite interplay on renal function and healthy aging.
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Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial.
Kragsnaes, MS, Kjeldsen, J, Horn, HC, Munk, HL, Pedersen, JK, Just, SA, Ahlquist, P, Pedersen, FM, de Wit, M, Möller, S, et al
Annals of the rheumatic diseases. 2021;(9):1158-1167
Abstract
OBJECTIVES Although causality remains to be established, targeting dysbiosis of the intestinal microbiota by faecal microbiota transplantation (FMT) has been proposed as a novel treatment for inflammatory diseases. In this exploratory, proof-of-concept study, we evaluated the safety and efficacy of FMT in psoriatic arthritis (PsA). METHODS In this double-blind, parallel-group, placebo-controlled, superiority trial, we randomly allocated (1:1) adults with active peripheral PsA (≥3 swollen joints) despite ongoing treatment with methotrexate to one gastroscopic-guided FMT or sham transplantation into the duodenum. Safety was monitored throughout the trial. The primary efficacy endpoint was the proportion of participants experiencing treatment failure (ie, needing treatment intensification) through 26 weeks. Key secondary endpoints were change in Health Assessment Questionnaire Disability Index (HAQ-DI) and American College of Rheumatology (ACR20) response at week 26. RESULTS Of 97 screened, 31 (32%) underwent randomisation (15 allocated to FMT) and 30 (97%) completed the 26-week clinical evaluation. No serious adverse events were observed. Treatment failure occurred more frequently in the FMT group than in the sham group (9 (60%) vs 3 (19%); risk ratio, 3.20; 95% CI 1.06 to 9.62; p=0.018). Improvement in HAQ-DI differed between groups (0.07 vs 0.30) by 0.23 points (95% CI 0.02 to 0.44; p=0.031) in favour of sham. There was no difference in the proportion of ACR20 responders between groups (7 of 15 (47%) vs 8 of 16 (50%)). CONCLUSIONS In this first preliminary, interventional randomised controlled trial of FMT in immune-mediated arthritis, we did not observe any serious adverse events. Overall, FMT appeared to be inferior to sham in treating active peripheral PsA. TRIAL REGISTRATION NUMBER NCT03058900.
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Pretreatment Prevotella-to-Bacteroides ratio and markers of glucose metabolism as prognostic markers for dietary weight loss maintenance.
Hjorth, MF, Christensen, L, Kjølbæk, L, Larsen, LH, Roager, HM, Kiilerich, P, Kristiansen, K, Astrup, A
European journal of clinical nutrition. 2020;(2):338-347
Abstract
BACKGROUND/OBJECTIVES Pre-treatment gut microbial Prevotella-to-Bacteroides (P/B) ratio and markers of glucose metabolism (i.e., fasting glucose and insulin) have been suggested as biomarkers for optimal weight management. However, both biomarkers need further validation, and the interactions between them for optimal weight management are largely unknown. To investigate differences in weight loss maintenance between subjects with low and high P/B ratio and the potential interactions with markers of glucose metabolism and dietary fiber intake. SUBJECTS/METHODS Following an 8-week weight loss period using meal replacement products, subjects losing ≥ 8% of their initial body weight were randomized to one of three protein supplements or maltodextrin for a 24-week weight maintenance period. Habitual diet was consumed along with the supplements expected to constitute 10-15% of total energy. For this analysis we stratified the participants into low and high strata based on median values of pre-intervention P/B ratio, pre-weight loss Homeostatic model assessment of insulin resistance (HOMA-IR) (<2.33 or > 2.33), and dietary fiber intake during the intervention (< 28.5 or > 28.5 g/10 MJ). RESULTS Regardless of weight maintenance regimen, subjects with high P/B ratio (n = 63) regained 1.5 (95% CI 0.4, 2.7) kg body weight (P = 0.007) more than subjects with low P/B ratio (n = 63). The regain among subjects with high P/B ratio was particular evident if HOMA-IR was high and dietary fiber intake was low. Consequently, in the high P/B strata, subjects with high HOMA-IR and low fiber intake (n = 17) regained 5.3 (95% CI 3.3, 7.3) kg (P < 0.001) more body weight compared with participants with low HOMA-IR and high fiber intake (n = 16). CONCLUSIONS Subjects with high P/B ratio were more susceptible to regain body weight compared with subjects with low P/B ratio, especially when dietary fiber intake was low and glucose metabolism was impaired. These observations underline that both the P/B ratio and markers of glucose metabolism should be considered as important biomarkers within personalized nutrition for optimal weight management.
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Response of the Human Milk Microbiota to A Maternal Prebiotic Intervention is Individual and Influenced by Maternal Age.
Padilha, M, Brejnrod, A, Danneskiold-Samsøe, NB, Hoffmann, C, de Melo Iaucci, J, Cabral, VP, Xavier-Santos, D, Taddei, CR, Kristiansen, K, Saad, SMI
Nutrients. 2020;(4)
Abstract
Maternal bacteria are shared with infants via breastfeeding. Prebiotics modulate the gut microbiota, promoting health benefits. We investigated whether the maternal diet supplementation with a prebiotic (fructooligosaccharides, FOS) could influence the milk microbiota. Twenty-eight lactating women received 4.5 g of fructooligosaccharides + 2 g of maltodextrin (FOS group) and twenty-five received 2 g of maltodextrin (placebo group) for 20 days. Breast-milk samples were taken before and after the intervention. The DNA from samples was used for 16S rRNA sequencing. No statistical differences between the groups were found for the bacterial genera after the intervention. However, the distances of the trajectories covered by paired samples from the beginning to the end of the supplementation were higher for the FOS group (p = 0.0007) indicating greater changes in milk microbiota compared to the control group. Linear regression models suggested that the maternal age influenced the response for FOS supplementation (p = 0.02). Interestingly, the pattern of changes to genus abundance upon supplementation was not shared between mothers. We demonstrated that manipulating the human milk microbiota through prebiotics is possible, and the maternal age can affect this response. .
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Interplay between food and gut microbiota in health and disease.
Danneskiold-Samsøe, NB, Dias de Freitas Queiroz Barros, H, Santos, R, Bicas, JL, Cazarin, CBB, Madsen, L, Kristiansen, K, Pastore, GM, Brix, S, Maróstica Júnior, MR
Food research international (Ottawa, Ont.). 2019;:23-31
Abstract
Numerous microorganisms colonize the human gastrointestinal tract playing pivotal roles in relation to digestion and absorption of dietary components. They biotransform food components and produce metabolites, which in combination with food components shape and modulate the host immune system and metabolic responses. Reciprocally, the diet modulates the composition and functional capacity of the gut microbiota, which subsequently influence host biochemical processes establishing a system of mutual interaction and inter-dependency. Macronutrients, fibers, as well as polyphenols and prebiotics are strong drivers shaping the composition of the gut microbiota. Especially, short-chain fatty acids produced from ingested fibers and tryptophan metabolites are key in modulating host immune responses. Since reciprocal interactions between diet, host, and microbiota are personal, understanding this complex network of interactions calls for novel use of large datasets and the implementation of machine learning algorithms and artificial intelligence. In this review, we aim to provide a base for future investigations of how interactions between food components and gut microbiota may influence or even determine human health and disease.
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Prevotella-to-Bacteroides ratio predicts body weight and fat loss success on 24-week diets varying in macronutrient composition and dietary fiber: results from a post-hoc analysis.
Hjorth, MF, Blædel, T, Bendtsen, LQ, Lorenzen, JK, Holm, JB, Kiilerich, P, Roager, HM, Kristiansen, K, Larsen, LH, Astrup, A
International journal of obesity (2005). 2019;(1):149-157
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Abstract
BACKGROUND/OBJECTIVES Individuals with high pre-treatment bacterial Prevotella-to-Bacteroides (P/B) ratio have been reported to lose more body weight on diets high in fiber than subjects with a low P/B ratio. Therefore, the aim of the present study was to examine potential differences in dietary weight loss responses between participants with low and high P/B. SUBJECTS/METHODS Eighty overweight participants were randomized (52 completed) to a 500 kcal/d energy deficit diet with a macronutrient composition of 30 energy percentage (E%) fat, 52 E% carbohydrate and 18 E% protein either high (≈1500 mg calcium/day) or low ( ≤ 600 mg calcium/day) in dairy products for 24 weeks. Body weight, body fat, and dietary intake (by 7-day dietary records) were determined. Individuals were dichotomized according to their pre-treatment P/B ratio derived from 16S rRNA gene sequencing of collected fecal samples to test the potential modification of dietary effects using linear mixed models. RESULTS Independent of the randomized diets, individuals with high P/B lost 3.8 kg (95%CI, 1.8,5.8; P < 0.001) more body weight and 3.8 kg (95% CI, 1.1, 6.5; P = 0.005) more body fat compared to individuals with low P/B. After adjustment for multiple covariates, individuals with high P/B ratio lost 8.3 kg (95% CI, 5.8;10.9, P < 0.001) more body weight when consuming above compared to below 30 g fiber/10MJ whereas this weight loss was 3.2 kg (95% CI, 0.8;5.5, P = 0.008) among individuals with low P/B ratio [Mean difference: 5.1 kg (95% CI, 1.7;8.6, P = 0.003)]. Partial correlation coefficients between fiber intake and weight change was 0.90 (P < 0.001) among individuals with high P/B ratio and 0.25 (P = 0.29) among individuals with low P/B ratio. CONCLUSIONS Individuals with high P/B lost more body weight and body fat compared to individuals with low P/B, confirming that individuals with a high P/B are more susceptible to weight loss on a diet rich in fiber.
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Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial.
Roager, HM, Vogt, JK, Kristensen, M, Hansen, LBS, Ibrügger, S, Mærkedahl, RB, Bahl, MI, Lind, MV, Nielsen, RL, Frøkiær, H, et al
Gut. 2019;68(1):83-93
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Plain language summary
Whole grain consumption has been linked with decreased risk of lifestyle-related diseases. While animal studies have shown the gut microbiome to be a mediator of metabolic health, human studies examining the effect of whole grain intake of the gut remain inconclusive. The aim of this study was to investigate the effects of a whole grain diet on the gut microbiome, gut functionality and biomarkers of metabolic health. In this randomised, controlled, crossover study, 50 participants completed two 8-week dietary intervention periods comprising of a whole grain diet and a refined grain diet with a 6-week washout period. Examinations were done at the beginning and end of each intervention period to assess anthropometry and various plasma and gut markers. This study found that a whole grain diet as compared with a refined grain diet reduced energy intake and body weight as well as circulating markers of inflammation. Contrary to the hypothesis, these benefits were all observed independent of changes in the gut microbiome. Based on these results, the authors conclude higher intake of whole grains should be recommended to those at risk of inflammation-related disease.
Abstract
OBJECTIVE To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. DESIGN 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. RESULTS 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. CONCLUSION Compared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation. TRIAL REGISTRATION NUMBER NCT01731366; Results.
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The Effect of Lean-Seafood and Non-Seafood Diets on Fecal Metabolites and Gut Microbiome: Results from a Randomized Crossover Intervention Study.
Schmedes, M, Brejnrod, AD, Aadland, EK, Kiilerich, P, Kristiansen, K, Jacques, H, Lavigne, C, Graff, IE, Eng, Ø, Holthe, A, et al
Molecular nutrition & food research. 2019;(1):e1700976
Abstract
SCOPE The impact of dietary protein types on the gut microbiome is scarcely studied. The aim of the present study is therefore to examine the effects of lean-seafood and non-seafood proteins on the gut microbiome composition and activity and elucidate potential associations to cardiovascular disease (CVD) risk factors. METHODS A crossover intervention study in which 20 healthy subjects consumed two diets that varied in protein source was conducted. 1 H NMR spectroscopy and 16S rDNA sequencing analyses were applied to characterize fecal metabolites and gut microbiota composition, respectively. RESULTS A twofold increase in fecal trimethylamine excretion was observed after the lean-seafood diet period. Circulating TAG and the total to high-density lipoprotein (HDL) cholesterol ratio as well as circulating TMAO levels were each associated with specific gut bacteria. Following the non-seafood diet period, a decreased relative abundance of Clostridium cluster IV and a tendency toward an increased Firmicutes/Bacteroidetes ratio were found. CONCLUSIONS Lean-seafood and non-seafood diets differentially modulate the gut microbiome composition and activity. Furthermore, the gut microbiota composition seems to affect circulating TMAO levels and CVD risk factors.
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A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults.
Hansen, LBS, Roager, HM, Søndertoft, NB, Gøbel, RJ, Kristensen, M, Vallès-Colomer, M, Vieira-Silva, S, Ibrügger, S, Lind, MV, Mærkedahl, RB, et al
Nature communications. 2018;(1):4630
Abstract
Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.