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Dietary Fibre Intake Is Associated with Serum Levels of Uraemic Toxins in Children with Chronic Kidney Disease.
El Amouri, A, Snauwaert, E, Foulon, A, Vande Moortel, C, Van Dyck, M, Van Hoeck, K, Godefroid, N, Glorieux, G, Van Biesen, W, Vande Walle, J, et al
Toxins. 2021;(3)
Abstract
Imbalanced colonic microbial metabolism plays a pivotal role in generating protein-bound uraemic toxins (PBUTs), which accumulate with deteriorating kidney function and contribute to the uraemic burden of children with chronic kidney disease (CKD). Dietary choices impact the gut microbiome and metabolism. The aim of this study was to investigate the relation between dietary fibre and gut-derived PBUTs in paediatric CKD. Sixty-one (44 male) CKD children (9 ± 5 years) were prospectively followed for two years. Dietary fibre intake was evaluated by either 24-h recalls (73%) or 3-day food records (27%) at the same time of blood sampling for assessment of total and free serum levels of different PBUTs using liquid chromatography. We used linear mixed models to assess associations between fibre intake and PBUT levels. We found an inverse association between increase in fibre consumption (g/day) and serum concentrations of free indoxyl sulfate (-3.1% (-5.9%; -0.3%) (p = 0.035)), free p-cresyl sulfate (-2.5% (-4.7%; -0.3%) (p = 0.034)), total indole acetic acid (IAA) (-1.6% (-3.0%; -0.3%) (p = 0.020)), free IAA (-6.6% (-9.3%; -3.7%) (p < 0.001)), total serum p-cresyl glucuronide (pCG) (-3.0% (-5.6%; -0.5%) (p = 0.021)) and free pCG levels (-3.3% (-5.8%; -0.8%) (p = 0.010)). The observed associations between dietary fibre intake and the investigated PBUTs highlight potential benefits of fibre intake for the paediatric CKD population. The present observational findings should inform and guide adaptations of dietary prescriptions in children with CKD.
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Gut Microbiome Profile After Pancreatectomy in Infants With Congenital Hyperinsulinism.
Vajravelu, ME, Lee, JJ, Mitteer, L, Zemel, BS, Bittinger, K, De León, DD
Pancreas. 2021;(1):89-92
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Abstract
OBJECTIVES The objective of this study was to characterize gut microbiome profiles of infants with congenital hyperinsulinism (HI) who underwent near-total or partial pancreatectomy for hypoglycemia management, as compared with healthy controls. METHODS A prospective observational cohort study was performed. Subjects were infants (0-6 months) with HI who underwent removal of pancreatic tissue for management of intractable hypoglycemia from February 2017 to February 2018 at the Children's Hospital of Philadelphia. Fecal samples were collected postoperatively, on full enteral nutrition. The gut microbiome of HI subjects was analyzed and compared with age-matched samples from healthy infants. RESULTS Seven subjects with ≥50% pancreatectomy and 6 with <50% pancreatectomy were included. α (within-sample) diversity was lowest among infants with ≥50% pancreatectomy (richness: false discovery rate, 0.003; Shannon index: false discovery rate, 0.01). β (between-sample) diversity (Bray-Curtis dissimilarity, P = 0.02; Jaccard distance, P = 0.001) differed across groups (≥ or <50% pancreatectomy, controls). Bifidobacteria and Klebsiella species were least abundant among infants with ≥50% pancreatectomy but did not differ between infants with <50% pancreatectomy and historical controls. CONCLUSIONS Infants with HI who underwent ≥50% pancreatectomy differed from age-matched infants in gut microbiome profile, whereas those with <50% pancreatectomy more closely resembled control profiles. The durability of this difference should be investigated.
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The Sulfur Microbial Diet Is Associated With Increased Risk of Early-Onset Colorectal Cancer Precursors.
Nguyen, LH, Cao, Y, Hur, J, Mehta, RS, Sikavi, DR, Wang, Y, Ma, W, Wu, K, Song, M, Giovannucci, EL, et al
Gastroenterology. 2021;(5):1423-1432.e4
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Abstract
BACKGROUND & AIMS Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (H2S), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking. METHODS We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses' Health Study II (1991-2015), a prospective cohort study with dietary assessment every 4 years through validated food frequency questionnaires and an assessment of dietary intake during adolescence in 1998. The sulfur microbial diet was characterized by intake high in processed meats, foods previously linked to CRC development, and low in mixed vegetables and legumes. Multivariable logistic regression for clustered data was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS We documented 2911 cases of early-onset adenoma. After adjusting for established risk factors, higher sulfur microbial diet scores were associated with increased risk for early-onset adenomas (ORquartile [Q]4 vs Q1, 1.31; 95% CI, 1.10-1.56, Ptrend = .02), but not serrated lesions. Compared with the lowest, women in the highest quartile of sulfur microbial diet scores had significantly increased risk of early-onset adenomas with greater malignant potential (ORQ4 vs Q1, 1.65 for villous/tubulovillous histology; 95% CI, 1.12-2.43; Ptrend = .04). Similar trends for early-onset adenoma were observed based on diet consumed during adolescence. In contrast, no clear association for adenomas was identified after age 50. CONCLUSIONS Our findings in a cohort of young women support a role for dietary interactions with gut sulfur-metabolizing bacteria in early-onset colorectal carcinogenesis, possibly beginning in adolescence.
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Overweight and underweight status are linked to specific gut microbiota and intestinal tricarboxylic acid cycle intermediates.
Wan, Y, Yuan, J, Li, J, Li, H, Yin, K, Wang, F, Li, D
Clinical nutrition (Edinburgh, Scotland). 2020;(10):3189-3198
Abstract
BACKGROUND & AIMS Intestinal short-chain fatty acids have been demonstrated to modulate host energy metabolism and are elevated in overweight and obese individuals. We hypothesized that other intestinal energy products especially tricarboxylic acid (TCA) cycle intermediates might also related to overweight status. In addition, little information is available regarding to the potential relationship between gut microbiota and underweight status. Therefore, the aim of this study was to investigate whether gut microbiota and intestinal energy metabolites differ in underweight, normal weight, and overweight individuals, and their correlations with host cardiometabolic risk factors. SUBJECTS/METHODS Gut microbiome, intestinal energy metabolites, circulating cardiometabolic risk factors, and proinflammatory markers were determined in 29 underweight, 67 normal weight, and 67 overweight adults. RESULTS The fecal concentrations of succinic acid, fumaric acid, malic acid, propionic acid, and adipic acid were significantly increased in the overweight individuals in parallel with a higher relative abundance of Veillonellacea after adjusting for multiple comparisons (all p < 0.05). The intestinal concentration of TCA cycle intermediate succinic acid was positively associated with body weight (r = 0.28, p = 0.04), and malic acid were in positive association with circulating total cholesterol, low-density lipoprotein cholesterol, and interleukin-1β (all r > 0.25, p < 0.05). Compared with the normal weight individuals, the gut microbial α-diversity was lower in the overweight (p = 0.007 for Shannon index and p = 0.009 for Ace index) and underweight (p = 0.05 for Shannon index and p = 0.08 for Ace index) groups. However, no significant differences in the overall gut microbiota composition were observed among the three groups. CONCLUSIONS Our findings revealed that low gut microbiota diversity was associated with both overweight and underweight status. Intestinal TCA cycle intermediates were associated with overweight development and might be potential markers for future studies related to gut microbiota and host cardiometabolic health.
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Metabolomic and Metataxonomic Fingerprinting of Human Milk Suggests Compositional Stability over a Natural Term of Breastfeeding to 24 Months.
Shenker, NS, Perdones-Montero, A, Burke, A, Stickland, S, McDonald, JAK, Alexander-Hardiman, K, Flanagan, J, Takats, Z, Cameron, SJS
Nutrients. 2020;(11)
Abstract
Sparse data exist regarding the normal range of composition of maternal milk beyond the first postnatal weeks. This single timepoint, observational study in collaboration with the 'Parenting Science Gang' citizen science group evaluated the metabolite and bacterial composition of human milk from 62 participants (infants aged 3-48 months), nearly 3 years longer than previous studies. We utilised rapid evaporative ionisation mass spectrometry (REIMS) for metabolic fingerprinting and 16S rRNA gene metataxonomics for microbiome composition analysis. Milk expression volumes were significantly lower beyond 24 months of lactation, but there were no corresponding changes in bacterial load, composition, or whole-scale metabolomic fingerprint. Some individual metabolite features (~14%) showed altered abundances in nursling age groups above 24 months. Neither milk expression method nor nursling sex affected metabolite and metataxonomic fingerprints. Self-reported lifestyle factors, including diet and physical traits, had minimal impact on metabolite and metataxonomic fingerprints. Our findings suggest remarkable consistency in human milk composition over natural-term lactation. The results add to previous studies suggesting that milk donation can continue up to 24 months postnatally. Future longitudinal studies will confirm the inter-individual and temporal nature of compositional variations and the use of donor milk as a personalised therapeutic.
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Small intestinal bacterial overgrowth: could it be associated with chronic abdominal pain in children with allergic diseases?
Peña-Vélez, R, Toro-Monjaraz, E, Avelar-Rodríguez, D, Ignorosa-Arellano, K, Zárate-Mondragón, F, Cervantes-Bustamante, R, Montijo-Barrios, E, Cadena-León, J, Ramírez-Mayans, J
Revista espanola de enfermedades digestivas. 2019;(12):927-930
Abstract
BACKGROUND AND AIMS small intestinal bacterial overgrowth (SIBO) is a well-known cause of chronic abdominal pain (CAP) during the pediatric age. On the other hand, children with a history of some allergic disorder present CAP more frequently. The aim of this study was to determine the association between the presence of allergic diseases and SIBO in patients diagnosed with CAP. MATERIALS AND METHODS this was an observational, analytical, retrospective study. Children with CAP who had undergone a lactulose hydrogen breath test to determine the presence of SIBO were included in the study. All patients underwent an evaluation for allergies by means of a skin prick test or the determination of specific IgE, according to clinical diagnosis. The study groups were established according to the presence of SIBO and the results of the allergic evaluation were statistically compared between the groups. RESULTS seventy patients were included (41 females and 29 males) and SIBO was diagnosed in 35 patients. In addition, 71.4% of children with SIBO were found to have an allergic disease, in contrast with 28.6% of children without SIBO (p = 0.001). The odds ratio for having any type of allergy in patients with SIBO was 5.45 (95% CI, 1.96-15.17; p = 0.001). CONCLUSIONS we found an association between SIBO and allergic disease, especially allergic rhinitis, cow's milk protein allergy and asthma. Thus, SIBO should be ruled out in pediatric patients with CAP and allergic disease.
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Dietary quality and the colonic mucosa-associated gut microbiome in humans.
Liu, Y, Ajami, NJ, El-Serag, HB, Hair, C, Graham, DY, White, DL, Chen, L, Wang, Z, Plew, S, Kramer, J, et al
The American journal of clinical nutrition. 2019;(3):701-712
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BACKGROUND Despite tremendous interest in modulating the microbiome to improve health, the association between diet and the colonic mucosa-associated gut microbiome in healthy individuals has not been examined. OBJECTIVE To investigate the associations between Healthy Eating Index (HEI)-2005 and the colonic mucosa-associated microbiota. METHODS In this cross-sectional observational study, we analyzed bacterial community composition and structure using 16S rRNA gene (V4 region) sequencing of 97 colonic mucosal biopsies obtained endoscopically from different colon segments of 34 polyp-free participants. Dietary consumption was ascertained using an FFQ. Differences in α- and β-diversity and taxonomic relative abundances between the higher and lower score of total HEI and its components were compared, followed by multivariable analyses. RESULTS The structure of the microbiota significantly differed by the scores for total HEI, total and whole fruits (HEI 1 and HEI 2), whole grains (HEI 6), milk products and soy beverages (HEI 7), and solid fat, alcohol, and added sugar (HEI 12). A lower score for total HEI and HEIs 2, 7, and 12 was associated with significantly lower richness. A lower score for total HEI was associated with significantly reduced relative abundance of Parabacteroides, Roseburia, and Subdoligranulum but higher Fusobacterium. A lower score for HEI 2 was associated with lower Roseburia but higher Bacteroides. A lower score for HEI 7 was associated with lower Faecalibacterium and Fusobacterium but higher Bacteroides. A lower score for HEI 12 was associated with lower Subdoligranulum but higher Escherichia and Fusobacterium (false discovery rate-adjusted P values <0.05). The findings were confirmed by multivariate analysis. Less abundant bacteria such as Alistipes, Odoribacter, Bilophila, and Tyzzerella were also associated with dietary quality. CONCLUSIONS A lower score for total HEI-2005 was significantly associated with reduced relative abundance of potentially beneficial bacteria but increased potentially harmful bacteria in the colonic mucosa of endoscopically normal individuals.
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Plasma microbiome-modulated indole- and phenyl-derived metabolites associate with advanced atherosclerosis and postoperative outcomes.
Cason, CA, Dolan, KT, Sharma, G, Tao, M, Kulkarni, R, Helenowski, IB, Doane, BM, Avram, MJ, McDermott, MM, Chang, EB, et al
Journal of vascular surgery. 2018;(5):1552-1562.e7
Abstract
OBJECTIVE Multiple studies have shown that gut microbes contribute to atherosclerosis, and there is mounting evidence that microbial metabolism of dietary nutrients influences pathophysiology. We hypothesized that indole- and phenyl-derived metabolites that originate solely or in part from bacterial sources would differ between patients with advanced atherosclerosis and age- and sex-matched controls without clinically apparent atherosclerosis. METHODS Plasma from the advanced atherosclerosis cohort (n = 100) was from patients who underwent carotid endarterectomy, open infrainguinal leg revascularization, or major leg amputation for critical limb ischemia. The controls (n = 22) were age- and sex-matched participants who had no peripheral arterial disease or history of stroke or myocardial infarction. Patients with chronic kidney disease were excluded. Metabolites and internal standards were measured using high-performance liquid chromatography and tandem mass spectrometry. RESULTS Plasma metabolite concentrations differed significantly between the advanced atherosclerosis and control cohorts. After adjustment for traditional atherosclerosis risk factors, indole (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.75-0.95; P = .004), tryptophan (OR, <0.001; 95% CI, <0.001-0.003; P < .001), indole-3-propionic acid (OR, 0.27; 95% CI, 0.019-0.91; P = .02), and indole-3-aldehyde (OR, 0.12; 95% CI, 0.014-0.92; P = .04) concentrations negatively associated with advanced atherosclerosis, whereas the kynurenine/tryptophan ratio (OR, 61.7; 95% CI, 1.9->999; P = .02) was positively associated. Furthermore, tryptophan and indole-3-propionic acid concentrations (Spearman coefficients of 0.63 and 0.56, respectively; P < .001) correlated with the ankle-brachial index, a surrogate for overall atherosclerotic disease burden. Fourteen patients experienced a major postoperative cardiac complication within 30 days in the advanced atherosclerosis cohort, which was associated with baseline kynurenine/tryptophan ratio (P = .001) and hippuric acid (P = .03). In a multivariate analysis, only the kynurenine/tryptophan ratio remained significantly associated with a postoperative cardiac complication (OR, 44.1; 95% CI, 3.3-587.1; P = .004). Twenty patients in the advanced atherosclerosis cohort experienced a major adverse cardiac event during the follow-up period, which was associated with hippuric acid (P = .002) and the kynurenine/tryptophan ratio (P < .001) at baseline. Both hippuric acid and the kynurenine/tryptophan ratio were independently associated with a major adverse cardiac event in multivariate analyses that included diabetes mellitus. CONCLUSIONS Specific microbe-derived metabolite signatures associate with advanced human atherosclerosis and postoperative cardiac complications. We suggest that these metabolites are potential novel biomarkers for atherosclerotic disease burden and that further investigation into mechanistic links between defined microbial metabolic pathways and cardiovascular disease is warranted.
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Phenylketonuric diet negatively impacts on butyrate production.
Verduci, E, Moretti, F, Bassanini, G, Banderali, G, Rovelli, V, Casiraghi, MC, Morace, G, Borgo, F, Borghi, E
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2018;(4):385-392
Abstract
BACKGROUND AND AIMS Phenylalanine (Phe) restricted diet, combined with Phe-free l-amino acid supplementation, is the mainstay of treatment for phenylketonuria (PKU). Being the diet a key factor modulating gut microbiota composition, the aim of the present paper was to compare dietary intakes, gut microbiota biodiversity and short chain fatty acids (SCFAs) production in children with PKU, on low-Phe diet, and in children with mild hyperphenylalaninemia (MHP), on unrestricted diet. METHODS AND RESULTS We enrolled 21 PKU and 21 MHP children matched for gender, age and body mass index z-score. Dietary intakes, including glycemic index (GI) and glycemic load (GL), and fecal microbiota analyses, by means of denaturing gradient gel electrophoresis (DGGE) and Real-time PCR were assessed. Fecal SCFAs were quantified by gas chromatographic analysis. RESULTS We observed an increased carbohydrate (% of total energy), fiber and vegetables intakes (g/day) in PKU compared with MHP children (p = 0.047), as well a higher daily GI and GL (maximum p < 0.001). Compared with MHP, PKU showed a lower degree of microbial diversity and a decrease in fecal butyrate content (p = 0.02). Accordingly, two of the most abundant butyrate-producing genera, Faecalibacterium spp. and Roseburia spp., were found significantly depleted in PKU children (p = 0.02 and p = 0.03, respectively). CONCLUSION The low-Phe diet, characterized by a higher carbohydrate intake, increases GI and GL, resulting in a different quality of substrates for microbial fermentation. Further analyses, thoroughly evaluating microbial species altered by PKU diet are needed to better investigate gut microbiota in PKU children and to eventually pave the way for pre/probiotic supplementations.
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Gut-Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet.
Pastori, D, Carnevale, R, Nocella, C, Novo, M, Santulli, M, Cammisotto, V, Menichelli, D, Pignatelli, P, Violi, F
Journal of the American Heart Association. 2017;(6)
Abstract
BACKGROUND Gut microbiota is emerging as a novel risk factor for atherothrombosis, but the predictive role of gut-derived lipopolysaccharide (LPS) is unknown. We analyzed (1) the association between LPS and major adverse cardiovascular events (MACE) in atrial fibrillation (AF) and (2) its relationship with adherence to a Mediterranean diet (Med-diet). METHODS AND RESULTS This was a prospective single-center study including 912 AF patients treated with vitamin K antagonists (3716 patient-years). The primary end point was a composite of MACE. Baseline serum LPS, adherence to Med-diet (n=704), and urinary excretion of 11-dehydro-thromboxane B2 (TxB2, n=852) were investigated. Mean age was 73.5 years; 42.9% were women. A total of 187 MACE (5.0% per year) occurred: 54, 59, and 74 in the first, second, and third tertile of LPS, respectively (log-rank test P=0.004). Log-LPS (hazard ratio 1.194, P=0.009), age (hazard ratio 1.083, P<0.001), and previous cerebrovascular (hazard ratio 1.634, P=0.004) and cardiac events (hazard ratio 1.822, P<0.001) were predictors of MACE. In the whole cohort, AF (versus sinus rhythm) (β 0.087, P=0.014) and low-density lipoprotein cholesterol (β 0.069, P=0.049) were associated with circulating LPS. Furthermore, Med-diet score (β -0.137, P<0.001) was predictive of log-LPS, with fruits (β -0.083, P=0.030) and legumes (β -0.120, P=0.002) negatively associated with log-LPS levels. Log-LPS and log-TxB2 were highly correlated (r=0.598, P<0.001). Log-LPS (β 0.574, P<0.001) and Med-diet score (β -0.218, P<0.001) were significantly associated with baseline urinary excretion of TxB2. CONCLUSIONS In this cohort of AF patients, LPS levels were predictive of MACE and negatively affected by high adherence to Med-diet. LPS may contribute to MACE incidence in AF by increasing platelet activation.