Markers of Bile Acid Metabolism in Pediatric Diarrhea Predominant Irritable Bowel Syndrome and Healthy Controls

Beinvogl, Beate C.; Manini, Mhd Louai; Camilleri, Michael; Donato, Leslie J.; Harmsen, William S.; Absah, Imad; Burch, Elizabeth; Schechter, Neil L.; Nurko, Samuel

doi:10.1097/mpg.0000000000003067

Cited by 8 publications

(11 citation statements)

References 46 publications

(82 reference statements)

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“…Previous studies revealed that intestinal microflora play a key role in maintaining metabolic balance ( 40 ). Most of metabolites in the blood were used to as biomarkers for diarrhea-related diseases ( 41 ). Thus, to study the fecal microbiota composition and plasma metabolomics characteristics of DHD calves may help to understand the pathogenesis of DHD and develop appropriate intervention strategies.…”

Section: Discussionmentioning

confidence: 99%

Integrated 16S rDNA Gene Sequencing and Untargeted Metabolomics Analyses to Investigate the Gut Microbial Composition and Plasma Metabolic Phenotype in Calves With Dampness-Heat Diarrhea

Yan

Zhang

et al. 2022

Front. Vet. Sci.

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Dampness-heat diarrhea (DHD), a common syndrome in Chinese dairy farms, is mainly resulted from digestive system disorders, and accompanied with metabolic disorders in some cases. However, the underlying mechanisms in the intestinal microbiome and plasma metabolome in calves with DHD remain unclear. In order to investigate the pathogenesis of DHD in calves, multi-omics techniques including the 16S rDNA gene sequencing and metabolomics were used to analyze gut microbial compositions and plasma metabolic changes in calves. The results indicated that DHD had a significant effect on the intestinal microbial compositions in calves, which was confirmed by changes in microbial population and distribution. A total of 14 genera were changed, including Escherichia-Shigella, Bacteroides, and Fournierella, in calves with DHD (P < 0.05). Functional analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations indicated that 11 metabolic functions (level 2) were significantly enriched in DHD cases. The untargeted metabolomics analysis showed that 440 metabolites including bilineurin, phosphatidylcholine, and glutamate were significantly different between two groups (VIP > 1 and P < 0.05), and they were related to 67 signal pathways. Eight signal pathways including alpha-linolenic acid, linoleic acid, and glycerophospholipid metabolism were significantly enriched (P < 0.05), which may be potential biomarkers of plasma in calves with DHD. Further, 107 pairs of intestinal microbiota-plasma metabolite correlations were determined, e.g., Escherichia-Shigella was significantly associated with changes of sulfamethazine, butyrylcarnitine, and 14 other metabolites, which reflected that metabolic activity was influenced by the microbiome. These microbiota-metabolite pairs might have a relationship with DHD in calves. In conclusion, the findings revealed that DHD had effect on intestinal microbial compositions and plasma metabolome in calves, and the altered metabolic pathways and microorganisms might serve as diagnostic markers and potential therapeutic targets for DHD in calves.

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Section: Discussionmentioning

confidence: 99%

Integrated 16S rDNA Gene Sequencing and Untargeted Metabolomics Analyses to Investigate the Gut Microbial Composition and Plasma Metabolic Phenotype in Calves With Dampness-Heat Diarrhea

Yan

Zhang

et al. 2022

Front. Vet. Sci.

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“…It has been suggested that, after early childhood, the ability to synthesize BAs and the patterns of BAs in children and adolescents are similar to those found in adults 7,8 …”

Section: Introductionmentioning

confidence: 86%

“…45 Given that it is estimated that 5% of the population in developed countries has chronic diarrhea of >4 weeks' duration at any point in time 46 and that BAD affects at least 25% of patients with chronic diarrhea, 18 it was proposed that ~1% of adults in Western countries have BAD. 47 Adolescents: In a cross-sectional study of adolescents 7 b. Post-cholecystectomy: A systematic review of 25 studies that included 3,388 patients showed only 9.1% of patients developed diarrhea after cholecystectomy, with two-thirds associated with evidence of BAD. 51 Similarly, in 125 consecutive patients who underwent laparoscopic cholecystectomy, 25.2% developed diarrhea at one week after surgery and 5.7% had diarrhea at 3 months.…”

Section: Epidemiology Of Idiopathic Bad and Associations With Other I...mentioning

confidence: 99%

“…Adolescents: In a cross‐sectional study of adolescents 7 which included 26 patients with IBS‐D and 56 healthy controls recruited in two pediatric tertiary care centers, 20% of pediatric patients had abnormal fasting serum C4. Moreover, a preliminary report 48 measured total fecal 48‐hour bile acids and percent of primary fecal BAs, which were significantly higher in 53 adolescents with IBS‐D compared to 41 healthy adolescent controls.…”

Section: Introductionmentioning

confidence: 99%

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Bile Acid Diarrhea in Adults and Adolescents

Camilleri

Nurko

2021

Neurogastroenterology Motil

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Background Bile acids are central to enterohepatic signaling pathways activated through natural receptors, farnesoid X receptor [FXR mediates synthesis of fibroblast growth factor‐19 (FGF‐19)], and G protein‐coupled bile acid receptor 1 (GPBAR1, also known as TGR5). Although bile acid diarrhea (BAD) is more commonly encountered in ileal resection or disease, there is evidence documenting “idiopathic” BAD in about 20% of adolescents and 30% of adults presenting with chronic, non‐bloody diarrhea often attributed to irritable bowel syndrome. Mechanism(s) leading to increased hepatic synthesis and colonic bile acid levels in “idiopathic” BAD include reduced synthesis of FGF‐19 by the ileal mucosa, or genetic variation in hepatocyte proteins klotho β and FGF receptor 4 (FGFR4) that mediate negative feedback of bile acid synthesis. Purpose: The objective of this review is to summarize the diagnosis of BAD in adults and adolescents. In addition to 75SeHCAT retention for diagnosis of BAD, studies have validated fasting serum 7αC4 and FGF‐19, respectively, by‐product and inhibitor of hepatic bile acid synthesis, as well as fecal bile acid measurements. These assays are widely available through reference laboratories, and they are being simplified (eg, measurement of primary fecal bile acids in a random stool sample). BAD has also been identified as a co‐factor contributing to persistent diarrhea in other diseases in remission including inflammatory bowel disease, microscopic colitis, celiac disease, and neuroendocrine tumors. In summary, advances in diagnosis of BAD provide opportunities for generalists and pediatric and adult gastroenterologists to provide targeted treatment for BAD presenting as chronic non‐bloody diarrhea.

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“…Using serum 7αC4 measurements, a two-center USA study [10] reported BAD in 20% of adolescents with irritable bowel syndrome with diarrhea (IBS-D), based on the 95th percentile value of 54.0 ng/mL among 56 healthy adolescents. The ULN for serum 7αC4 in adults and adolescents in the USA was similar (adolescents 54.0 ng/mL, adults 52.8 ng/mL); moreover, 28% of adolescents with IBS-D had low FGF19 values.…”

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confidence: 99%