Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05112497 |
| Other study ID # |
MoMmy-CD |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 10, 2020 |
| Est. completion date |
August 2025 |
Study information
| Verified date |
May 2023 |
| Source |
Chinese University of Hong Kong |
| Contact |
Siew Chien Ng, PhD |
| Phone |
852-35053996 |
| Email |
siewchienng[@]cuhk.edu.hk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis
(UC), are caused by the loss of mucosal tolerance towards the commensal microbiota resulting
in inflammatory responses. Both CD and UC are difficult to manage clinically, and their
incidences are increasing worldwide especially in newly industrialized countries. The
etiology of these disorders is multifactorial, influenced by the complex interactions of
genes, the immune system, intestinal microbiota, and the external environment. Studies have
shown that there is a higher disease transmission rate from mothers with IBD than from
fathers. It is well established that IBD is also associated with perturbations of gut
microbiota composition. Early childhood is a golden age for microbiota manipulation to
prevent disease. Studying microbiota at this golden age also allow us to dissect the
development of a faulty microbiota and identify therapeutic targets to reverse it and cure
diseases that are already developed. New evidence suggests that the gastrointestinal tract of
new-borns becomes colonized with bacteria while in the womb, with the presence of different
microbes. The source of these microbes is of continued interest because the initial
intestinal colonization is believed to play a crucial role in the priming of the mucosal
immune system and may predispose to the development of immune-mediated diseases, such as IBD,
later in life. Overall, the microbiome structures in mother-babies across healthy and IBD
populations are largely underexplored.
A recent study discovered a novel mechanism of vertically transmitted protection of the
new-born. The researchers found that bacteria in the mother's intestine during gestation can
drive later innate maturation of the neonatal gut in the absence of colonization, through the
transfer of specific bacterial metabolites to the foetus and via mother's milk. Study
demonstrated that the effects of the gut microbiota on postnatal immune maturation are not
simply due to colonization of the new-born after birth. Given the complexity of microbes
present in the gestational gut, it will be exciting to learn whether there are other modules
of priming induced by distinct microbes and their metabolites. Along these lines, it is
tempting to speculate that this transgenerational effect represents a predictive adaptive
response whereby mothers prepare the neonates for specific challenges that they are likely to
encounter based on gestational environmental cues, not only by microbial colonisation but
also by metabolite transfer. Meanwhile, it is unknown regarding whether there are
abnormalities in the metabolome as well as its mother-to-infant transfer in IBD. Those
results indicate that the metabolomic profiles are altered in IBD mother's breast milk, which
may transfer to infants and influence their development and health.
Description:
Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis
(UC), are caused by the loss of mucosal tolerance towards the commensal microbiota resulting
in inflammatory responses. Both CD and UC are difficult to manage clinically, and their
incidences are increasing worldwide especially in newly industrialized countries. The
etiology of these disorders is multifactorial, influenced by the complex interactions of
genes, the immune system, intestinal microbiota, and the external environment. Studies have
shown that there is a higher disease transmission rate from mothers with IBD than from
fathers.[47] It is well established that IBD is also associated with perturbations of gut
microbiota composition. Early childhood, when the microbiota is less mature and more
malleable, is a golden age for microbiota manipulation to prevent disease. Studying
microbiota at this golden age also allow us to dissect the development of a faulty microbiota
and identify therapeutic targets to reverse it and cure diseases that are already developed.
New evidence suggests that the gastrointestinal tract of new-borns becomes colonized with
bacteria while in the womb[1], with the presence of different microbes reported in amniotic
fluid[2, 3], umbilical cord blood[4], as well as placental and foetal membranes[5, 6]. The
source of these microbes is of continued interest because the initial intestinal colonization
is believed to play a crucial role in the priming of the mucosal immune system and may
predispose to the development of immune-mediated diseases, such as IBD, later in life[7]. Our
pilot study on several mother-baby samples showed that at the order level, Caudovirales
predominated in the viral communities of breast milk and meconium with relative abundance
above 95%. However, in the viral community of placenta, the Caudovirales only occupied
approximately 50%, concomitant with the emergence of eukaryotic viruses such as Ortervirles
(average 27.5%) and Herpesvirales (average 9.3%). Overall, the microbiome structures in
mother-babies across healthy and IBD populations are largely underexplored.
A recent study discovered a novel mechanism of vertically transmitted protection of the
new-born. The researchers found that bacteria in the mother's intestine during gestation can
drive later innate maturation of the neonatal gut in the absence of colonization, through the
transfer of specific bacterial metabolites to the foetus and via mother's milk [8]. Gomez de
Agu ero et al. (2016) clearly demonstrated that the effects of the gut microbiota on
postnatal immune maturation are not simply due to colonization of the new-born after
birth[9]. They show this in a simplified model of gestational monocolonization with E. coli
whereby AhR ligands derived from this bacterium drive a distinct early postnatal intestinal
developmental program[9]. Given the complexity of microbes present in the gestational gut, it
will be exciting to learn whether there are other modules of priming induced by distinct
microbes and their metabolites. Along these lines, it is tempting to speculate that this
transgenerational effect represents a predictive adaptive response whereby mothers prepare
the neonates for specific challenges that they are likely to encounter based on gestational
environmental cues, not only by microbial colonisation but also by metabolite transfer.
Meanwhile, it is unknown regarding whether there are abnormalities in the metabolome as well
as its mother-to-infant transfer in IBD. To address this question, we began with a pilot
study on breast milk metablome profiling, employing untargeted metabolomics approach by
liquid chromatography-mass spectrometry (LC-MS). The results showed a total of 1,318
Negative-mode features and 1,418 Positive features discriminatory between IBD (4UC, 3 CD)
mothers and healthy mothers, indicative of broad metabolic differences between them. Those
significantly changed metabolites were involved in arginine and proline metabolism as well as
tyrosine metabolism according to pathway enrichment analysis. Those results indicate that the
metabolomic profiles are altered in IBD mother's breast milk, which may transfer to infants
and influence their development and health.
