Clinical Trial Details
— Status: Not yet recruiting
Administrative data
NCT number |
NCT04836754 |
Other study ID # |
Covid-19 |
Secondary ID |
|
Status |
Not yet recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
May 1, 2022 |
Est. completion date |
September 1, 2022 |
Study information
Verified date |
December 2021 |
Source |
Halic University |
Contact |
Aysu Y Yildiz Karaahmet, PhD Student |
Phone |
05414679620 |
Email |
aysuyildiz[@]halic.edu.tr |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Coronavirus disease (Covid-19) is a new public health crisis threatening humanity caused by
SARS-CoV-2. Although it originated in China's Hubei province in late 2019, it has spread to
many countries around the world. Although Covid-19 first caused infection by affecting the
lung, current data showed that the gastrointestinal tract was also affected by detecting
viral RNA in Covid-19-infected human intestinal epithelial cells and feces. The association
has been confirmed by showing that patients hospitalized with COVID-19 have significant
changes in intestinal bacterioma. These changes have been characterized by a significant
reduction in gut microbiome (BM) diversity associated with gastrointestinal complaints of the
acute phase of infection (e.g. abdominal pain, nausea, vomiting, diarrhea), depletion of
beneficial bacterial symbionts, and enrichment of opportunistic pathogens (e.g.
Streptococcus, Rothia, Actinomyces). In particular, recent studies have evidence that
patients with Covid-19 are more prone to a dysbiosis profile of the gut microbiota, infected
individuals present irregular gut microbiota, and even dysbiosis (disruption of microbiota
balance) in the gut microbiota.
The first case reports reported in China suggested that there was no virus found in amniotic
fluid, umbilical cord blood, throat swabs of the newborn, placenta, vaginal fluid, and breast
milk samples infected with Covid-19. The latest data indicate that there is no vertical
transmission to the fetus, and so far, no viruses have been found in the cord blood of
newborns born from Covid-19 positive pregnant women, nasal sampling and amniotic fluid and
placentas of pregnant women. However, the effect of intestinal microbial structure affected
by Covid-19 on breast milk microbiota and the effect of a dysbiosis to occur on infant health
or the effect of the healing properties of breast milk on Covid-19 are still not clearly
known. This views are that intestinal microbial colonization originating from the
gastrointestinal system affected by Covid-19 will affect breast milk microbial colonization.
However, there is no study on this subject.
For this purpose, aim in this study was to determine the breast milk microbiome and
biologically active proteins (secretory immunoglobulin A (sIgA), lysozyme, lactoferrin,
osteoprotegerin (OPG), leptin, adiponectin and β-endorphin (b-) levels of mothers who had
Covid-19 with healthy mothers. will be compared.
Description:
Coronavirus disease (Covid-19) is a new public health crisis threatening humanity caused by
SARS-CoV-2. Although it originated in China's Hubei province in late 2019, it has spread to
many countries around the world (Wang et al., 2020). In patients with Covid-19, severe cases
of respiratory, hepatic, gastrointestinal and neurological complications and a complex
clinical picture that eventually turns into death are observed (Guo et al., 2020; Li et al.,
2020). The underlying pathophysiological mechanisms are complex and multifactorial, and have
been summarized as a hyper-response of the immune system that causes an inflammatory /
cytokine storm (Li et al., 2020).
Although Covid-19 caused infection by first affecting the lung, current data showed that the
gastrointestinal system was also affected by detecting viral RNA in human intestinal
epithelial cells and feces infected with Covid-19 (Cheng et al., 2002; Wu et al., 2020). This
is thought to be caused by the relationship between the gut microbiota and the lung axis.
Studies have demonstrated that Bacteroidetes and Firmicutes bacteria, which are dominant in
intestinal colonization, are also dominant in the lung (Bacteroidetes, Firmicutes and
Proteobacteria) (Zhang et al., 2020). In short, while intestinal microbiota causes lung
diseases, respiratory tract virus infections also cause confusion in the intestinal
microbiota. In fact, many studies have shown that respiratory infections are associated with
a change in the composition of the gut microbiota (Groves et al., 2020). The high-throughput
16S rRNA amplicon sequence and shotgun metagenomic sequence analyzes demonstrated that
hospitalized COVID-19 patients had significant changes in the intestinal bacterioma, and the
relationship was confirmed. These changes have been characterized by a significant reduction
in gut microbiome (BM) diversity associated with gastrointestinal complaints of the acute
phase of infection (e.g. abdominal pain, nausea, vomiting, diarrhea), depletion of beneficial
bacterial symbionts, and enrichment of opportunistic pathogens (e.g. Streptococcus, Rothia,
Actinomyces) (Gu et al., 2020; Zuo et al., 2020). In particular, recent studies have evidence
that patients with Covid-19 are more prone to dysbiosis profile of the gut microbiota,
infected individuals present irregular gut microbiota and even dysbiosis (disruption of
microbiota balance) in the gut microbiota (Gu et al., 2020; Zuo et al., 2020 ).
The intestinal flora plays a protective role in many metabolic and immune functions of the
host, i.e. against pathogenic colonization of the virus, including training and strengthening
the immune system to fight infections (Fernandes et al., 2019). Looking at the composition of
the gut flora, it is highly dynamic from birth and is shaped by different environmental
factors (e.g. diet, breast milk pre- / probiotics, drugs) resulting in various microbial-host
functions (Koppel, Maini Rekdal, Balskus, 2017; Weiss, Hennet, 2017) . Human gastrointestinal
tract (GIS), 2000 'classified into 12 different phyla, the most common (> 90%) Proteobacteria
(Gram-negative), Firmicutes (Gram-positive), Actinobacteria (Gram-positive) and Bacteroidetes
(Gram-negative) phyla. It is believed that human intestinal viroma, consisting of both
prokaryotic and eukaryotic viruses, shares important information with all microbial
components and can affect overall human health by shaping the structure and function of the
intestinal community (Cani , 2018; Garmaeva et al., 2019).
Breast milk is the bioactive component that most affects the formation of neonatal microbial
colonization in the postnatal period and provides us with information about human future
health. Breast milk is not only the best nutritional source for babies, but it is also known
to contain immune components such as secretory antibodies, immune cells, antimicrobial
proteins (such as lactoferrin and lysozyme), cytokines, and human milk oligosaccharide.
Before the 2000s, breast milk was thought to be sterile, and the presence of bacteria
indicated contamination or infection. However, several researchers have shown that breast
milk has been colonized with bacteria since pregnancy and contains commensal bacteria in
particular. In a study, it was found that Proteobacteria (Gram-negative), Firmicutes
(Gram-positive), Actinobacteria (Gram-positive) and Bacteroidetes (Gram-negative) phyla,
which are dominant in maternal intestinal colonization, are among the breast milk microbes
Firmicutes, Proteobacteria Bacteroidetes and Actinobacteria. It has been proved that breast
milk originates from the mother's gastrointestinal system in this case (Ojo et al., 2018). In
addition, the same study showed that there were bacteria sharing the same strains in the
mother's intestine, the baby's intestine and breast milk, and the mother's commensal bacteria
had vertical transmission to the infant's intestine through breast milk.
Human coronaviruses were defined as enveloped, positive-sensitive, single-stranded RNA
viruses, first described in 1965 (Tyrrell and Bynoe, 1965). There are seven identified
strains known to infect humans. Four of the strains (alphacoronaviruses 229E, NL63, OC43, and
betacoronavirus HKU1) are ubiquitous in humans and cause the common cold. There are questions
about the effect of human coronaviruses on pregnant, maternal and infant health and the
transmission status is not clear. Pregnancy alters a woman's immune system and makes them
more susceptible to infections. However, there is currently no evidence that pregnant women
are more likely to be affected by COVID 19 or serious illness as a result, compared to the
general population. Although the mechanism is unclear, there is limited evidence that one of
the four strains (229E) mentioned above can be transmitted vertically from mothers to infants
(Gagneur et al., 2008). The presence of this virus (229E) in neonatal gastric samples
suggests that a possible mechanism for infection is through breast milk, but this study did
not specifically evaluate breast milk (Gagneur et al., 2008).
The first case reports reported in China suggested that there was no virus in amniotic fluid,
umbilical cord blood, throat swabs of the newborn, placenta, vaginal fluid, and breast milk
samples infected with Covid-19 (Johns et al, 2013). The latest data indicate that there is no
vertical transmission to the fetus, and so far, no viruses have been found in the cord blood
of newborns born from Covid-19 positive pregnant women, nasal sampling and amniotic fluid and
placentas of pregnant women. However, the effect of intestinal microbial structure affected
by Covid-19 on breast milk microbiota and the effect of a dysbiosis to occur on infant health
or the effect of the healing properties of breast milk on Covid-19 are still not clearly
known. This study views are that intestinal microbial colonization originating from the
gastrointestinal system affected by Covid-19 will affect breast milk microbial colonization.
However, there is no study on this subject.
Breast milk is a golden nutrient that provides critical nutrients and bioactive compounds
that support growth and immune development during infancy. Variation in milk components and
bioactive compounds as a result of demographic and genetic factors, the mother's lifestyle
and exposure has both positive and negative effects on infant health (Abrahamsson et al.,
2009; de Andres et al., 2018; Johns et al. , 2013). It has been reported that babies who are
breastfed have a dynamic gut microbiome and the incidence of some diseases has decreased
(Abrahamsson et al., 2009; de Andres et al., 2018). In addition to macro and micronutrients
and bioactive compounds, breast milk contains many types of bacteria. Lactoferrin is one of
the important bioactive components in breast milk. The lactoferrin in breast milk can support
a local intestinal environment, such as microbiota that strengthens the innate defenses of
newborns. Lactoferrin promotes the growth of favorable gut microbiota and the proliferation
of enterocytes through direct anti-inflammatory and immunomodulatory effects.
The action of lactoferrin on cell receptors prevents viral damage, surface accumulation and
cell entry. In this way, it protects and strengthens mucosal immunity and intestinal
epithelial barrier. It is believed that breast milk, particularly lactoferrin, exhibits
potential antiviral effects. The challenge is how effective they are in preventing viral
infections such as coronaviruses (de Andres et al., 2018).
We believe early breastfeeding provides vital prevention during viral outbreaks due to the
high value of colostrum and breast milk and the specific role of lactoferrin, but more
clinical evidence is needed. These effects and mechanisms have not been tested on Covid-19,
but we can consider this approach as they affect other coronaviruses.
In addition, breast milk components containing approximately 109 bacteria are known to affect
the baby's own microbiome and immune system (Ruiz et al., 2019). However, contrary to what is
known, breast milk microbiota and its influencing factors are only recently being discovered
and understood (McGuire & McGuire, 2017; Moossavi et al., 2019; Williams et al., 2017). In
addition, while exploring the effects of certain components in breast milk on the nursing
baby, we tend to ignore the dynamic state and effect of other components that could greatly
affect the results. While it was known that the microbiome, which we cannot see with the
naked eye, could affect individuals, it was not thought that our world would change that much
with a single virus, Covid-19. While the microbiome we often ignore because it is invisible
to us reminds us of a world that has profound effects on our health and well-being, how does
Covid-19 affect this world and breast milk? For this purpose, aim in this study was to
determine the breast milk microbiome and biologically active proteins (secretory
immunoglobulin A (sIgA), lysozyme, lactoferrin, osteoprotegerin (OPG), leptin, adiponectin
and β-endorphin (b-) levels of mothers who had Covid-19 with healthy mothers. will be
compared.
A total of 20 mothers (10 mothers) and healthy (10 mothers) who had Covid-19 in the last
month of pregnancy between April 2021 and June 2021 will be included in the study and the
mothers will be given an appointment on the 15th day and will start with taking breast milk
samples and 16sRNA microbiota. Analyzing the microbiota content of breast milk and the levels
of biologically active proteins (secretory immunoglobulin A (sIgA), lysozyme, lactoferrin,
osteoprotegerin (OPG), leptin, adiponectin and β-endorphin (b)) in breast milk content will
be evaluated.
Hypothesis in this study is that breast milk microbiota will differ in variety and
composition in mothers who have had Covid-19. In this direction, as a result of the research;
Conducting microbial analysis to evaluate the content of microbiota and bioactive components
by taking the milk of mothers who have had Covid-19 during pregnancy,
- In line with the results obtained, it is planned to give correct advice and guidance in
accordance with an urgent problem.