Other than exposure to gluten and genetic compatibility, the gut microbiome has been suggested to be involved in celiac disease (CD) pathogenesis by mediating interactions between ...gluten/environmental factors and the host immune system. However, to establish disease progression markers, it is essential to assess alterations in the gut microbiota before disease onset. Here, a prospective metagenomic analysis of the gut microbiota of infants at risk of CD was done to track shifts in the microbiota before CD development. We performed cross-sectional and longitudinal analyses of gut microbiota, functional pathways, and metabolites, starting from 18 mo before CD onset, in 10 infants who developed CD and 10 matched nonaffected infants. Cross-sectional analysis at CD onset identified altered abundance of six microbial strains and several metabolites between cases and controls but no change in microbial species or pathway abundance. Conversely, results of longitudinal analysis revealed several microbial species/strains/pathways/metabolites occurring in increased abundance and detected before CD onset. These had previously been linked to autoimmune and inflammatory conditions (e.g.,
,
sp.,
, tryptophan metabolism, and metabolites serine and threonine). Others occurred in decreased abundance before CD onset and are known to have anti-inflammatory effects (e.g.,
,
, and
). Additionally, we uncovered previously unreported microbes/pathways/metabolites (e.g.,
, high mannose-type
-glycan biosynthesis, and serine) that point to CD-specific biomarkers. Our study establishes a road map for prospective longitudinal study designs to better understand the role of gut microbiota in disease pathogenesis and therapeutic targets to reestablish tolerance and/or prevent autoimmunity.
Intestinal failure-associated liver disease (IFALD) is a threatening complication for children on long-term parenteral nutrition because of intestinal failure. When progressive and intractable, it ...may jeopardize intestinal rehabilitation and lead to combined liver and intestinal transplantation. The institution of dedicated intestinal failure centers has dramatically decreased the incidence of such complication. IFALD may rapidly fade away if very early management aimed at preventing progression to end-stage liver disease is provided. In this review, we address the etiology and risk factors of IFALD in order to introduce pillars of prevention (nutritional management and catheter-related infections control). The latest evidence of therapeutic strategies, such as medical and surgical treatments, is also discussed.
Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive ...treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients < 10 years. TDM data were collected retrospectively in 14 centres. Children treated with IFX were included if IFX was started as IBD treatment at age < 10 years (young patients, YP) and PK data were available. Older IBD patients aged 10–18 years were used as controls (older patients, OP). Two hundred and fifteen paediatric inflammatory bowel disease (PIBD) patients were eligible for the study (110 < 10 year; 105 ≥ 10 years). Median age was 8.3 years (IQR 6.9–8.9) in YP compared with 14.3 years (IQR 12.8–15.6) in OP at the start of IFX. At the start of maintenance treatment, 72% of YP had trough levels below therapeutic range (< 5.4 μg/mL). After 1 year of scheduled IFX maintenance treatment, YP required a significantly higher dose per 8 weeks compared with OP (YP; 9.0 mg/kg (IQR 5.0–12.9) vs. OP; 5.5 mg/kg (IQR 5.0–9.3);
p
< 0.001). The chance to develop antibodies to infliximab was relatively lower in OP than YP (0.329 (95% CI − 1.2 to − 1.01);
p
< 0.001), while the overall duration of response to IFX was not significantly different (after 2 years 53% (
n
= 29) in YP vs. 58% (
n
= 45) in OP;
p
= 0.56).
Conclusion
: Intensification of the induction scheme is suggested for PIBD patients aged < 10 years.
What is Known?
•Infliximab trough levels of paediatric IBD patients are influenced by several factors as dosing scheme, antibodies and inflammatory markers.
•In 4.5–30% of the paediatric IBD patients, infliximab treatment was stopped within the first year.
What is New?
•The majority of young PIBD (< 10 years) have inadequate IFX trough levels at the start of maintenance treatment.
•Young PIBD patients (< 10 years) were in need of a more intensive treatment regimen compared with older paediatric patients during 1 year of IFX treatment.
•The chance to develop antibodies to infliximab was relatively higher in young PIBD patients (< 10 years).
The Celiac Disease Genomic, Environmental, Microbiome and Metabolomic (CDGEMM) study is an international prospective birth cohort in children at-risk of developing celiac disease (CD). The CDGEMM ...study has been designed to take a multi-omic approach to predicting CD onset in at-risk individuals. Participants are required to have a first-degree family member with biopsy diagnosed CD and must be enrolled prior to the introduction of solid food. Participation involves providing blood and stool samples longitudinally over a period of five years as well as answering questionnaires related to the participant, their family, and environment. Recruitment and data collection have been ongoing since 2014. As of 2022 we have a total of 554 participants and the average age of the cohort is 56.4 months. A total of 54 participants have developed positive antibodies for CD and 31 have confirmed CD. Approximately 80% of the 54 participants with CD have developed it by 3 years of age. To date we have identified several microbial strains, pathways, and metabolites occurring in increased abundance and detected before CD onset, which have previously been linked to autoimmune and inflammatory conditions while others occurred in decreased abundance before CD onset and are known to have anti-inflammatory effects. Our ongoing analysis includes expanding our metagenomic and metabolomic analyses, evaluating environmental risk factors linked to CD onset, and mechanistic studies investigating how alterations in the microbiome and metabolites may protect against or contribute to CD development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
7.
Reply Norsa, Lorenzo
Gastroenterology (New York, N.Y. 1943),
05/2021, Letnik:
160, Številka:
6
Journal Article
The purpose of this study was to identify possible serum biomarkers predicting celiac disease (CD) onset in children at risk.
A subgroup from an ongoing, international prospective study of children ...at risk of CD was classified according to an early trajectory of deamidated gliadin peptides (DGPs) immunoglobulin (Ig) G and clinical outcomes (CD, potential CD, and CD autoimmunity).
Thirty-eight of 325 children developed anti-tissue transglutaminase IgA antibody (anti-tTG IgA) seroconversion. Twenty-eight of 38 children (73.6%) showed an increase in anti-DGPs IgG before their first anti-tTG IgA seroconversion.
Anti-DGPs IgG can represent an early preclinical biomarker predicting CD onset in children at risk.
Inflammatory bowel diseases (IBD) affect the gastrointestinal tract: they include Crohn's disease (CD) and ulcerative colitis (UC). Each has a different phenotypic spectrum, characterized by ...gastrointestinal and extra-intestinal manifestations. People living with IBD are very interested in diet, but little is known about the impact of diet on these patients; no guidelines are available yet. In this review, we analyze the dietary patterns of patients with IBD and the approach to the choices of foods both in adults and pediatric patients. Very often, IBD patients report an intentional avoidance of gluten to manage the disease; furthermore, a proportion of IBD patients believe that dairy products worsen their symptoms and that avoidance may help the disease. They have a low compliance with the Mediterranean Diet, which is considered to have potential benefits but is little used in practice. In conclusion, the review underscores the pivotal role of nutritional counselling in IBD patients, and the importance of future clinical studies to evaluate the beneficial effects of dietary recommendations in the management of IBD.
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