scholarly journals Association of Gut Microbiota and Metabolites With Disease Progression in Children With Biliary Atresia

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Song ◽  
Li-Ying Sun ◽  
Zhi-Jun Zhu ◽  
Lin Wei ◽  
Wei Qu ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Biliary Atresia ◽  
Disease Progression ◽  
Lithocholic Acid ◽  
Early Stage ◽  
Intestinal Microbiome ◽  
Metagenomic Sequencing ◽  
Clinical Indicators ◽  
Microbiota Structure

Background and AimsBiliary atresia is the most common cause of liver disease and liver transplantation in children. The accumulation of bile acids in hepatocytes and the stimulation of the intestinal microbiome can aggravate the disease progression. This study investigated changes in the composition of the gut microbiota and its metabolites in biliary atresia and the possible effects of these changes on disease progression.MethodsStool samples of biliary atresia at different disease stages and matched control individuals were collected (early stage: 16 patients, 16 controls; later stage: 16 patients, 10 controls). Metagenomic sequencing was performed to evaluate the gut microbiota structure. Untargeted metabolomics was performed to detect and analyze the metabolites and bile acid composition.ResultsA disturbed gut microbiota structure occurred in the early and later stages of biliary atresia. Klebsiella, Streptococcus, Veillonella, and Enterococcus have always been dominant. The abundance of V. atypica displayed significant changes between the early and later stages of biliary atresia. Combined with clinical indicators, Spearman’s analysis showed that Klebsiella and Veillonella atypica strongly correlated with liver enzymes. Enterococcus faecium had an enormously positive relationship with lithocholic acid derivatives. Metabolites involved in tryptophan metabolism were changed in the patients with biliary atresia, which had a significant association with stool V. atypica and blood total bilirubin (p < 0.05).ConclusionsThe liver damage of biliary atresia was directly or indirectly exacerbated by the interaction of enriched Klebsiella (K. pneumoniae), Veillonella (V. atypica), and Enterococcus (E. faecium) with dysmetabolism of tryptophan and bile acid.

scholarly journals The Potential Prebiotic Berberine Combined With Methimazole Improved the Therapeutic Effect of Graves’ Disease Patients Through Regulating the Intestinal Microbiome

2022 ◽  
Vol 12 ◽  
Author(s):  
Zhe Han ◽  
Chaoping Cen ◽  
Qianying Ou ◽  
Yonggui Pan ◽  
Jiachao Zhang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Thyroid Function ◽  
Pathogenic Bacteria ◽  
Intestinal Microbiome ◽  
Graves Disease ◽  
Metagenomic Sequencing ◽  
Clinical Indicators ◽  
Intestinal Microbes ◽  
Metabolism Disorder ◽  
Diffuse Goiter

Graves’ disease, a typical metabolism disorder, causes diffuse goiter accompanied by ocular abnormalities and ocular dysfunction. Although methimazole (MI) is a commonly used drug for the treatment of GD, the efficacy of methimazole is only limited to the control of clinical indicators, and the side effects of MI should be seriously considered. Here, we designed a 6-month clinical trial that divided the patients into two groups: a methimazole group (n=8) and a methimazole combined with potential prebiotic berberine group (n=10). The effects of both treatments on thyroid function and treatment outcomes in patients with GD were assessed by thyroid index measurements and gut microbiota metagenomic sequencing. The results showed that the addition of berberine restored the patients’ TSH and FT3 indices to normal levels, whereas MI alone restored only FT3. In addition, TRAb was closer to the healthy threshold at the end of treatment with the drug combination. MI alone failed to modulate the gut microbiota of the patients. However, the combination of berberine with methimazole significantly altered the microbiota structure of the patients, increasing the abundance of the beneficial bacteria Lactococcus lactis while decreasing the abundance of the pathogenic bacteria Enterobacter hormaechei and Chryseobacterium indologenes. Furthermore, further mechanistic exploration showed that the addition of berberine resulted in a significant upregulation of the synthesis of enterobactin, which may have increased iron functioning and thus restored thyroid function. In conclusion, methimazole combined with berberine has better efficacy in patients with GD, suggesting the potential benefit of berberine combined with methimazole in modulating the composition of intestinal microbes in the treatment of GD, providing new strong evidence for the effectiveness of combining Chinese and Western drugs from the perspective of modulating the intestinal microbiota.

scholarly journals Effects of Previous Kasai Surgery on Gut Microbiota and Bile Acid in Biliary Atresia With End-Stage Liver Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Wei Song ◽  
Li-Ying Sun ◽  
Zhi-Jun Zhu
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Gut Microbiota ◽  
Biliary Atresia ◽  
Alternative Pathway ◽  
Bile Acid Metabolism ◽  
Cholestatic Liver Disease ◽  
Metagenomic Sequencing ◽  
End Stage Liver Disease ◽  
End Stage

Background and Aims: Biliary atresia (BA) is the most common cholestatic liver disease in neonates. Although the Kasai procedure can improve temporary biliary drainage in some cases, complications and liver fibrosis still develop. Liver transplantation is the ultimate treatment. The current study aimed to investigate the effect of previous Kasai surgery on gut microbiota and bile acid in BA with end-stage liver disease.Methods: Patients with BA with end-stage liver disease were divided into two groups according to whether they had previously undergone Kasai surgery (non-Kasai: n = 8, post-Kasai: n = 8). Metagenomic sequencing and ultraperformance liquid chromatography/tandem mass spectrometry were performed to identify the gut microbiota and bile acid.Results: Previous Kasai surgery had some effects on gut microbiota and bile acid in BA with end-stage liver disease. In the gut microbiome, the differential species were mainly distributed at the species level. Veillonella atypica had a significant increase in the non-Kasai group (P < 0.05). Bacteroides spp., Prevotella spp., Barnesiella spp., Parabacteroides spp., Heliobacterium spp., Erysipelatoclostridium spp. and Diaporthe spp. were increased in the post-Kasai group (P < 0.05). Concerning functional profiles, methionine biosynthesis was enriched in the non-Kasai group, while pyridoxal biosynthesis and riboflavin biosynthesis were enriched in the post-Kasai group (linear discriminant analysis > 2, P < 0.05). In stools, 17 bile acids were distinctly elevated in the post-Kasai group, such as cholic acid, chenodeoxycholic acid, β-muricholic acid and tauro α-muricholate (P < 0.05). Spearman correlation test showed that V. atypica had an enormously positive correlation with liver enzymes. Faecalibacterium prausnitzii and Escherichia coli were associated with derivatives of the alternative pathway of bile acid metabolism.Conclusion: Previous Kasai surgery can improve the gut microbiota and bile acid in patients with BA with end-stage liver disease. This improvement contributes to maintaining the intestinal barrier.

Fecal Microbiome and Bile Acid Metabolome in Adult Short Bowel Syndrome

2021 ◽  
Author(s):  
Harold J. Boutte ◽  
Jacqueline Chen ◽  
Todd N. Wylie ◽  
Kristine M. Wylie ◽  
Yan Xie ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Short Bowel Syndrome ◽  
Lithocholic Acid ◽  
Intestinal Failure ◽  
Patient Specific ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Fecal Microbiome ◽  
Short Bowel

Background & Aims: Loss of functional small bowel surface area causes short bowel syndrome (SBS), intestinal failure, and parenteral nutrition (PN) dependence. The gut adaptive response following resection may be difficult to predict, and it may take up to two years to determine which patients will wean from PN. Here we examined features of gut microbiota and bile acid (BA) metabolism in determining adaptation and ability to wean from PN. Methods: Stool and sera were collected from healthy controls and from SBS patients (n=52) with ileostomy, jejunostomy, ileocolonic and jejunocolonic anastomoses fed with PN plus enteral nutrition or who were exclusively enterally fed. We undertook 16S rRNA gene sequencing, BA profiling and 7α-hydroxy-4-cholesten-3-one (C4) quantitation with LC-MS/MS, and serum amino acid analyses. Results: SBS patients exhibited altered gut microbiota with reduced gut microbial diversity compared to healthy controls. We observed differences in the microbiomes of SBS patients with ileostomy vs. jejunostomy, jejunocolonic vs. ileocolonic anastomoses, and PN-dependence compared to those who weaned from PN. Stool and serum BA composition and C4 concentrations were also altered in SBS patients, reflecting adaptive changes in enterohepatic BA cycling. Stools from patients who weaned from PN were enriched in secondary BAs including deoxycholic acid and lithocholic acid. Conclusions: Shifts in gut microbiota and BA metabolites may generate a favorable luminal environment in select SBS patients, promoting the ability to wean from PN. Pro-adaptive microbial species and select BA may provide novel targets for patient-specific therapies for SBS.

scholarly journals Characteristics of Gut Microbiota in Children With Biliary Atresia After Liver Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Song ◽  
Li-Ying Sun ◽  
Zhi-Jun Zhu ◽  
Lin Wei ◽  
Wei Qu ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Gut Microbiota ◽  
Biliary Atresia ◽  
Control Level ◽  
Control Group ◽  
Metagenomic Sequencing ◽  
Polyamine Biosynthesis ◽  
Fecal Samples ◽  
Linear Discriminant ◽  
Significant Difference

Background and AimsBiliary atresia (BA) is an idiopathic neonatal cholestasis and is the most common indication in pediatric liver transplantation (LT). Previous studies have suggested that the gut microbiota (GM) in BA is disordered. However, the effect of LT on gut dysbiosis in patients with BA has not yet been elucidated.MethodsPatients with BA (n = 16) and healthy controls (n = 10) were recruited. In the early life of children with BA, Kasai surgery is a typical procedure for restoring bile flow. According to whether BA patients had previously undergone Kasai surgery, we divided the post-LT patients into the with-Kasai group (n = 8) and non-Kasai group (n = 8). Fecal samples were collected in both the BA and the control group; among BA patients, samples were obtained again 6 months after LT. A total of 40 fecal samples were collected, of which 16 were pre-LT, 14 were post-LT (8 were with-Kasai, 6 were non-Kasai), and 10 were from the control group. Metagenomic sequencing was performed to evaluate the GM.ResultsThe Kruskal-Wallis test showed a statistically significant difference in the number of genes between the pre-LT and the control group, the pre-LT and the post-LT group (P < 0.05), but no statistical difference between the post-LT and the control group. Principal coordinate analysis also showed that the microbiome structure was similar between the post-LT and control group (P > 0.05). Analysis of the GM composition showed a significant decrease in Serratia, Enterobacter, Morganella, Skunalikevirus, and Phifllikevirus while short chain fatty acid (SCFA)-producing bacteria such as Roseburia, Blautia, Clostridium, Akkermansia, and Ruminococcus were increased after LT (linear discriminant analysis > 2, P < 0.05). However, they still did not reach the normal control level. Concerning functional profiles, lipopolysaccharide metabolism, multidrug resistance, polyamine biosynthesis, GABA biosynthesis, and EHEC/EPEC pathogenicity signature were more enriched in the post-LT group compared with the control group. Prior Kasai surgery had a specific influence on the postoperative GM.ConclusionLT partly improved the GM in patients with BA, which provided new insight into understanding the role of LT in BA.

scholarly journals Sexually Dimorphic Regulation of Gut Microbiota and Body Weight by a Naturally Occurring Flavonoid

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 472-472
Author(s):  
Priyanka Sharma ◽  
Guojun Wu ◽  
Hong Ye ◽  
Yan Y Lam ◽  
Deeptha Kumaraswamy ◽  
...  
Keyword(s):  
Body Weight ◽  
Gut Microbiota ◽  
Intestinal Microbiome ◽  
Sexually Dimorphic ◽  
Female Mice ◽  
Diet Induced Obesity ◽  
Naturally Occurring ◽  
Principal Coordinates ◽  
Brown Adipose ◽  
Microbiota Structure

Abstract Objectives 7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that is being actively investigated as a therapeutic modality in the treatment of neurological disorders. A recent study also indicated that oral DHF supplementation protected female but not male mice from diet-induced obesity. However, the mechanisms underlying this sexually-dimorphic effects of DHF were not known. The aim of the work is to investigate the mechanisms underlying sex-specific effects of flavonoid. Methods Age-matched male and female mice were given ad libitum access to high fat-diet and drinking water containing vehicle or DHF for 12 weeks. Body weights, body composition, food, and water intake, were assessed. Immunohistological analysis, immunohistochemistry staining, plasma triglycerides, plasma bile acids, and hepatic lipids were investigated. Fresh fecal samples were collected, genomic DNA was extracted and hypervariable region V4 of the 16S rRNA gene was amplified. Gut microbiota structure was evaluated using alpha diversity indices and beta diversity distance metrices. Principal coordinates analysis (PCoA) was performed using the R “ape” package to visualize differences in gut microbiota structure between treatment groups along principal coordinates that accounted for most of the variations. Results Oral administration of DHF, remodels the intestinal microbiome of female, but not male, prior to divergence in body weight. This is concomitant with increase in brown adipose tissue thermogenesis, mediated by increased expression of UCP1 and Pgc -1α protecting the female mice from diet-induced obesity. Conclusions This study demonstrates sexually-dimorphic effects of a clinically relevant natural compound. Importantly, it points to a role for sex-dependent remodeling of the intestinal microbiome as a mechanism for weight control in females. Thus, our discoveries pave the way for personalized nutrition strategies that account for sex differences in metabolism. Funding Sources NIH.

scholarly journals Duration of Persistent Atrial Fibrillation Is Associated with Alterations in Human Gut Microbiota and Metabolic Phenotypes

mSystems ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Kun Zuo ◽  
Jing Li ◽  
Pan Wang ◽  
Ye Liu ◽  
Zheng Liu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gut Microbiota ◽  
Early Stage ◽  
Persistent Atrial Fibrillation ◽  
Metabolic Profiles ◽  
Metagenomic Sequencing ◽  
Microbial Function ◽  
Distinct Structure ◽  
The Common ◽  
The Relationship

ABSTRACT Atrial fibrillation (AF) has been shown to be associated with disordered gut microbiota (GM). The underlying factors governing persistent AF (psAF) are not well understood, and the association between AF duration and GM profiles remains to be characterized. Thus, the present study aimed at investigating the dysbiosis of GM in patients with short and long psAF duration and illuminating the relationship between the GM and psAF maintenance. Based on metagenomic sequencing and metabolomic analyses, we assessed the metabolic and GM signature in 12 patients with psAF of <12 months (Pers<12m), eight patients with psAF of >12 months (Pers>12m), and 20 controls. We found that the GM in patients with both Pers<12m and Pers>12m was significantly perturbed, with an elevated microbial diversity, distinct structure, and discrepant composition. Although Pers<12m and Pers>12m patients shared a large number of common bacteria with controls, including 84 genera and 404 species, certain bacteria were differently enriched at different AF durations. Furthermore, disturbance in gut microbial function and GM-linked metabolic alterations were detected in both the Pers<12m and Pers>12m groups. The connection of GM and metabolites with psAF is consistent with interaction and potential modulation of host metabolic pathways due to GM dysbiosis with AF persistence. Our results showed that patients of the Pers<12m and Pers>12m groups shared many common disordered GM and metabolic features, which might occur in early disease, while prolonged psAF duration was related to certain unique alterations. Preventative strategies targeting GM and microbial metabolites for early intervention to treat AF patients are highly warranted. IMPORTANCE Atrial fibrillation was associated with a disordered gut microbiota in previous research. However, the gut microbiota signature of patients at different stages of atrial fibrillation remains largely unknown. We sought to determine whether the shift in the gut microbiota and metabolic profiles occurs early and remains stable or develops gradually during atrial fibrillation. We found that patients with persistent atrial fibrillation of <12 months and persistent atrial fibrillation of >12 months shared most of the common features of gut microbiota dysbiosis. However, some distinctive and progressive alterations in the gut microbiota and metabolic structure, which may contribute to the progression of atrial fibrillation, were identified. The present study provides a comprehensive description of the dysbiotic gut microbiota and metabolic profiles in patients of short and long persistent atrial fibrillation, and our findings may help identify therapeutic strategies targeting the gut microbiota to treat atrial fibrillation at an early stage.

scholarly journals A metabolic pathway for bile acid dehydroxylation by the gut microbiome

2019 ◽  
Author(s):  
Masanori Funabashi ◽  
Tyler L. Grove ◽  
Victoria Pascal ◽  
Yug Varma ◽  
Molly E. McFadden ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Lithocholic Acid ◽  
Primary Biliary Cholangitis ◽  
Bile Acid Pool ◽  
Secondary Bile Acid ◽  
Acid Pool ◽  
Road Map ◽  
Host Physiology

ABSTRACTThe gut microbiota synthesize hundreds of molecules, many of which are known to impact host physiology. Among the most abundant metabolites are the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA), which accumulate at ~500 μM and are known to block C. difficile growth1, promote hepatocellular carcinoma2, and modulate host metabolism via the GPCR TGR53. More broadly, DCA, LCA and their derivatives are a major component of the recirculating bile acid pool4; the size and composition of this pool are a target of therapies for primary biliary cholangitis and nonalcoholic steatohepatitis. Despite the clear impact of DCA and LCA on host physiology, incomplete knowledge of their biosynthetic genes and a lack of genetic tools in their native producer limit our ability to modulate secondary bile acid levels in the host. Here, we complete the pathway to DCA/LCA by assigning and characterizing enzymes for each of the steps in its reductive arm, revealing a strategy in which the A-B rings of the steroid core are transiently converted into an electron acceptor for two reductive steps carried out by Fe-S flavoenzymes. Using anaerobic in vitro reconstitution, we establish that a set of six enzymes is necessary and sufficient for the 8-step conversion of cholic acid to DCA. We then engineer the pathway into Clostridium sporogenes, conferring production of DCA and LCA on a non-producing commensal and demonstrating that a microbiome-derived pathway can be expressed and controlled heterologously. These data establish a complete pathway to two central components of the bile acid pool, and provide a road map for deorphaning and engineering pathways from the microbiome as a critical step toward controlling the metabolic output of the gut microbiota.

scholarly journals Gut microbiota and metabolites of α-synuclein transgenic monkey models with early stage of Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yaping Yan ◽  
Shuchao Ren ◽  
Yanchao Duan ◽  
Chenyu Lu ◽  
Yuyu Niu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Metabolic Pathways ◽  
Rhesus Monkeys ◽  
Early Stage ◽  
Glyceric Acid ◽  
Metagenomic Sequencing ◽  
Phosphorylation Reaction ◽  
Hydroxyphenylacetic Acid

AbstractParkinson’s disease (PD) is the second most prevalent neurodegenerative disease. However, it is unclear whether microbiota and metabolites have demonstrated changes at early PD due to the difficulties in diagnosis and identification of early PD in clinical practice. In a previous study, we generated A53T transgenic monkeys with early Parkinson’s symptoms, including anxiety and cognitive impairment. Here we analyzed the gut microbiota by metagenomic sequencing and metabolites by targeted gas chromatography. The gut microbiota analysis showed that the A53T monkeys have higher degree of diversity in gut microbiota with significantly elevated Sybergistetes, Akkermansia, and Eggerthella lenta compared with control monkeys. Prevotella significantly decreased in A53T transgenic monkeys. Glyceric acid, L-Aspartic acid, and p-Hydroxyphenylacetic acid were significantly elevated, whereas Myristic acid and 3-Methylindole were significantly decreased in A53T monkeys. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (KO0131) and the oxidative phosphorylation reaction (KO2147) were significantly increased in metabolic pathways of A53T monkeys. Our study suggested that the transgenic A53T and α-syn aggregation may affect the intestine microbiota and metabolites of rhesus monkeys, and the identified five compositional different metabolites that are mainly associated with mitochondrial dysfunction may be related to the pathogenesis of PD.

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