CONCLUSIONS
Gut microbiota played a protective role in the prevention of chicken
colibacillosis and the pharmacological action of baicalin. The altered
specific gut bacterial and/or metabolites may be served as indicators to
predict the occurrence and prognosis of chicken colibacillosis. Our
findings may provide a paradigm for the mechanistic studies of compounds
and aid the exploration of the mechanisms and pathways underlying the
function of herbal medicines.
Key words : Chicken colibacillosis, baicalin, gut microbiota,
metabolites
Introduction
Chicken
colibacillosis,
a localized and systemic disease caused by avian Escherichia coli(APEC), causedhuge economic losses to the poultry industry and
threatened food security, which is responsible for the use of very
significant volumes of antibiotics in commercial poultry
farming(Peek, Halkes, Tomassen, Mes, &
Landman, 2013). Despite being known for over a century and studied for
a long time, the pathogenesis of colibacillosis remains poorly
understood. Up until now, it is widely accepted that the systemic form
of colibacillosis from a respiratory origin that induces colisepticemia.
Colonization of the trachea and air sacs is considered the first step of
a systemic infection by APEC, followed by the colonization of the lung,
liver and the pericardium(Guabiraba &
Schouler, 2015). Therefore, we considered that targeting the
respiratory infection stage of APEC and stopping the APEC from entering
the blood circulation may be an effective way to prevent and cure
colibacillosis.
The gut microbiota, consisting of mostly bacteria, plays a positive
player in the host defence system, regulating mucosal immunity and
systemic immunity(Noverr & Huffnagel,
2004; Trompette et al., 2014). Recent
studies have reported that gut microbiota modulated the pulmonary immune
during respiratory disease through what is often called “gut-lung
axis”(Budden et al., 2017;
Dumas, Bernard, Poquet, Lugo-Villarino, &
Neyrolles, 2018). Many respiratory diseases occurred and developed
accompanying with intestinal flora
alteration(Dickson, Martinez, & Huffnagle,
2014). Moreover, the gut microbiota contributed the protection against
pneumococcal pneumonia and Mycobacterium tuberculosis in
lung(Dumas, Corral, et al., 2018;
Schuijt et al., 2016). What role does gut
microbiota play in chicken colibacillosis, however, remains elusive.
Scutellaria
baicalensis , a Chinese traditional medicine, has been widely used to
treat various diseases, such as influenza, pneumonia, dysentery, and
cancer(Z. L. Wang et al., 2018).
Baicalin, a naturally occurring constituent, was extracted from the dry
roots of Scutellaria baicalensis and possessed anti-inflammatory,
anti-allergic, anti-oxidant, hepatoprotective, and anti-tumor
activities. In the previous study, we have found that baicalin had a
protective effect against colibacillosis. However, the precise mechanism
is still unclear. Recent report has manifested that metabolic activities
of intestinal microflora may be of a great importance for herbal
medicines to express the pharmacological
effects(An et al., 2019). Myung-Ah Jung
et.al, has proved that orally
administered baicalin was metabolized to baicalein and oroxylin A by
intestinal microbiota, which enhances its anti-inflammatory effect by
inhibiting NF-κB activation(Jung, Jang,
Hong, Hana, & Kim, 2012a). Furthermore, modern studies discovered that
the administrated herbal medicines also interacted with gut microbiota
and regulated the composition of the flora to improve the disease, such
as diabetes mellitus(Creely et al., 2007).
Hence, we speculated that gut microbiota played an important role in the
process of baicalin exerting pharmacological effects. Similarly,
baicalin may regulate the gut microbiota and its metabolite to protect
chicken against colibacillosis.
Therefore, to understand the role of gut microbiota in the chicken
colibacillosis and pharmacological effect of baicalin, as well as
explore the protective mechanisms of baicalin on colibacillosis, we
utilized APEC-O78 to establish the model of colibacillosis and
applied
the broad-spectrum antibiotic (Abx) to deplete the gut microbiota. Then,
we measured the secretion of inflammatory cytokines, gene expression of
inflammatory cytokines and tight junction, histopathological changes and
viscera index. Furthermore, after orally administration of baicalin, we
measure the alteration of gut microbiota and its metabolite by 16s rDNA
sequencing and ultrahigh-performance liquid chromatography (LC-MS).