Impact Of A Phe-Restricted Diet On Gut Health In Children With PKU
Impact Of A Phenylalanine-Restricted Diet On The Microbiota Composition And Metabolome Of Children With PKU
Phenylketonuria (PKU) is an inherited disorder of phenylalanine (Phe) metabolism. The mainstay of treatment is a Phe-restricted diet, which aims to maintain blood Phe concentrations within the recommended range and prevent neurological complications. Some individuals with PKU respond to pharmacological treatments, including sapropterin, a synthetic form of tetrahydrobiopterin (BH4), or sepiapterin. These treatments may increase Phe tolerance and allow a less restrictive diet.
Diet is an important determinant of gut microbiota composition and function. However, the effects of the Phe-restricted diet and pharmacologically enabled dietary relaxation on the gut microbiota in PKU remain poorly understood.
This observational study includes children and adolescents with PKU aged 3-17 years attending Birmingham Children's Hospital. Participants include those managed exclusively with a Phe-restricted diet, those receiving sapropterin, and those receiving sepiapterin. One healthy household control is recruited for each participant with PKU.
Faecal samples are collected for shotgun metagenomic sequencing and metabolite profiling. Dietary intake, gastrointestinal symptoms, stool characteristics, clinical information, and PKU treatment are also assessed.
The study investigates whether gut microbiota composition, microbial functional potential, and faecal metabolite profiles differ between participants managed with a Phe-restricted diet, those receiving pharmacological treatment, and healthy household controls. The findings may improve understanding of the relationships between PKU treatment, dietary restriction, gastrointestinal health, and the gut microbiome and may inform future nutritional strategies for individuals with PKU.
연구 개요
상태
정황
상세 설명
This is a single-centre, cross-sectional observational study conducted at Birmingham Children's Hospital. The study investigates the association between phenylketonuria (PKU) treatment, degree of dietary restriction, gastrointestinal health, and the composition and functional potential of the gut microbiota.
Children and adolescents aged 3-17 years with early-treated PKU are recruited into one of three cohorts according to their existing clinical management: treatment with a phenylalanine-restricted diet alone (anticipated n=30), treatment with sapropterin alongside an individualised phenylalanine-restricted diet (anticipated n=30), or treatment with sepiapterin alongside an individualised phenylalanine-restricted diet (anticipated n=14). Participants receiving sapropterin or sepiapterin have been receiving treatment for at least three months and have achieved at least a 100% increase in natural protein tolerance compared with their pre-treatment prescription. Treatment allocation, medication dosage, and dietary management are determined as part of routine clinical care and are not assigned or modified by the study.
One healthy household control is recruited for each participant with PKU. Household controls are aged 3 years or older and do not have PKU or another inherited metabolic disorder. Recruiting controls from the same household aims to reduce the influence of shared environmental factors, including living conditions and food availability, when comparing gut microbiota profiles. The anticipated total enrolment is 148 participants, comprising 74 participants with PKU and 74 household controls.
Each participant provides a single faecal sample. Samples are stored at -80°C and analysed using shotgun metagenomic sequencing to characterise microbial taxonomic composition, within-sample diversity, between-sample community differences, and microbial functional potential. Taxonomic profiles are assessed at multiple levels, including phylum, genus, and species. Functional annotation is used to characterise microbial genes, enzymes, and metabolic pathways.
Dietary intake is assessed using a 24-hour dietary recall, including natural protein intake, protein substitute intake, dietary fibre intake, and consumption of special low-protein foods. Gastrointestinal symptoms are assessed using the age-appropriate self-report or parent-proxy version of the PedsQL Gastrointestinal Symptoms Module, and stool form is assessed using the Bristol Stool Form Scale. Relevant demographic and clinical information, including age, sex, anthropometric measurements, PKU treatment, and metabolic control, is also collected.
The findings from this study may support the development of nutritional strategies and protein substitutes that more effectively promote gastrointestinal and metabolic health in individuals with PKU.
연구 유형
등록 (추정된)
연락처 및 위치
연구 연락처
- 이름: Anita MacDonald, PhD
- 전화번호: +44 121 333 9999
- 이메일: anita.macdonald@nhs.net
연구 연락처 백업
- 이름: Catarina Rodrigues, MSc
- 전화번호: +44 121 472 1377
- 이메일: catarina.rodrigues1@nhs.net
연구 장소
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Birmingham
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Birmingham, Birmingham, 영국, B4 6NH
- 모병
- Birmingham Children's Hospital
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연락하다:
- Anita MacDonald, PhD
- 전화번호: +44 121 333 9999
- 이메일: anita.macdonald@nhs.net
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참여기준
자격 기준
공부할 수 있는 나이
- 어린이
건강한 자원 봉사자를 받아들입니다
샘플링 방법
연구 인구
Children and adolescents aged 3-17 years with early-treated phenylketonuria receiving clinical care at Birmingham Children's Hospital are recruited into one of three cohorts according to their current treatment: a phenylalanine-restricted diet alone, sapropterin, or sepiapterin.
One healthy household control aged 3 years or older, without phenylketonuria or another inherited metabolic disorder, is recruited for each participant with phenylketonuria. All participants are enrolled according to predefined eligibility criteria.
설명
Inclusion Criteria:
Participants with PKU:
- Aged 3-17 years.
- Confirmed diagnosis of phenylketonuria following newborn screening.
- Receiving ongoing clinical management for PKU.
- For the diet-only cohort: managed with standard phenylalanine-restricted dietary treatment and not receiving sapropterin or sepiapterin.
- For the sapropterin cohort: receiving sapropterin for at least three consecutive months and having achieved at least a 100% increase in natural protein tolerance compared with the pre-treatment prescription.
- For the sepiapterin cohort: receiving sepiapterin for at least three consecutive months and having achieved at least a 100% increase in natural protein tolerance compared with the pre-treatment prescription.
Healthy household controls:
- Aged 3 years or older.
- Living in the same household as a participating child or adolescent with PKU.
- No known diagnosis of PKU or another inherited metabolic disorder.
Exclusion Criteria:
- Congenital malformations.
- Chronic gastrointestinal disease.
- Endocrine, liver, or kidney disease.
- Other chronic medical conditions likely to affect gut microbiota composition.
- Following a therapeutic diet for a medical condition other than PKU within the six months before stool sample collection.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
코호트 및 개입
그룹/코호트 |
개입 / 치료 |
|---|---|
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PKU - Diet Only
Children and adolescents aged 3-17 years with early-treated phenylketonuria who are managed exclusively with a phenylalanine-restricted diet and are not receiving sapropterin or sepiapterin.
Participants provide a faecal sample and undergo dietary, clinical, gastrointestinal symptom, and stool assessments.
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Participants are managed with a phenylalanine-restricted diet and prescribed protein substitutes as part of their usual clinical care.
They are not receiving sapropterin or sepiapterin.
Dietary treatment is not assigned or modified by this observational study.
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PKU - Sapropterin
Children and adolescents aged 3-17 years with early-treated phenylketonuria who have been receiving sapropterin for at least 3 months and have achieved at least a 100% increase in natural protein tolerance compared with before treatment.
Sapropterin treatment is not assigned as part of this observational study.
Participants provide a faecal sample and undergo dietary, clinical, gastrointestinal symptom, and stool assessments.
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Participants receive sapropterin as part of their usual clinical care, alongside an individualised phenylalanine-restricted diet.
Sapropterin treatment and dosage are prescribed independently of this observational study and are not assigned or modified by the investigators.
다른 이름들:
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PKU - Sepiapterin
Children and adolescents aged 3-17 years with early-treated phenylketonuria who have been receiving sepiapterin for at least 3 months and have achieved at least a 100% increase in natural protein tolerance compared with before treatment.
Sepiapterin treatment is not assigned as part of this observational study.
Participants provide a faecal sample and undergo dietary, clinical, gastrointestinal symptom, and stool assessments.
|
Participants receive sepiapterin as part of their existing clinical management, alongside an individualised phenylalanine-restricted diet.
Sepiapterin treatment and dosage are determined independently of this observational study and are not assigned or modified by the investigators.
다른 이름들:
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Healthy Household Controls
Healthy household members without phenylketonuria who are recruited at a ratio of one control for each participant with phenylketonuria.
Controls provide a faecal sample and complete the relevant dietary, gastrointestinal symptom, and stool assessments.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Faecal gut microbiota taxonomic composition assessed by shotgun metagenomic sequencing
기간: At enrolment (single faecal sample collection)
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Taxonomic profiles, expressed as the relative abundance of microbial taxa at phylum, genus, and species levels, are derived from shotgun metagenomic sequencing of one faecal sample per participant.
Profiles are compared among participants with PKU managed by a phenylalanine-restricted diet alone, sapropterin, or sepiapterin and healthy household controls.
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At enrolment (single faecal sample collection)
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Faecal gut microbiota alpha diversity assessed by shotgun metagenomic sequencing
기간: At enrolment, based on a single faecal sample
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Within-sample microbial diversity is assessed from shotgun metagenomic sequencing data using alpha-diversity indices, including Shannon, Simpson, Chao1, ACE, and observed species.
Alpha-diversity measures are compared across the study cohorts.
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At enrolment, based on a single faecal sample
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Faecal gut microbiota beta diversity assessed by shotgun metagenomic sequencing
기간: At enrolment, based on a single faecal sample
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Differences in overall microbial community composition between participants are assessed using beta-diversity measures derived from shotgun metagenomic sequencing data, including Bray-Curtis dissimilarity.
Microbial community profiles are compared across the study cohorts.
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At enrolment, based on a single faecal sample
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Microbial functional potential assessed by shotgun metagenomic sequencing
기간: At enrolment, based on a single faecal sample
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Microbial genes and functional pathways are characterised from shotgun metagenomic sequencing data using functional annotation databases.
The relative abundance of microbial genes, enzymes, and metabolic pathways is compared across the study cohorts.
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At enrolment, based on a single faecal sample
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Gastrointestinal symptom burden assessed using the PedsQL Gastrointestinal Symptoms Module
기간: At enrolment, based on a single faecal sample
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Gastrointestinal symptoms are assessed using the age-appropriate self-report or parent-proxy version of the PedsQL Gastrointestinal Symptoms Module.
Total and individual symptom-domain scores are calculated, with lower scores indicating a greater gastrointestinal symptom burden, and compared across the study cohorts.
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At enrolment, based on a single faecal sample
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Stool form assessed using the Bristol Stool Form Scale
기간: At enrolment, based on a single faecal sample
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Usual stool form is classified using the Bristol Stool Form Scale, ranging from type 1, representing separate hard lumps, to type 7, representing entirely liquid stool.
Stool-form distributions are compared across the study cohorts.
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At enrolment, based on a single faecal sample
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Dietary intake assessed using a 24-hour dietary recall
기간: At enrolment, based on a single faecal sample
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Dietary intake is assessed using a 24-hour dietary recall.
Nutrient and food-group measures, including natural protein intake, protein substitute intake, dietary fibre intake, and consumption of special low-protein foods, are estimated and compared across the study cohorts.
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At enrolment, based on a single faecal sample
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공동 작업자 및 조사자
수사관
- 수석 연구원: Anita MacDonald, PhD, Birmingham Children's Hospital
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- IRAS project ID: 353831
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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