The importance of the complex interplay between the microbiome and mucosal immunity, particularly within the respiratory tract, has gained significant attention due to its potential implications for the severity and progression of lung diseases. Therefore, this review summarizes the specific interactions through which the respiratory tract-specific microbiome influences mucosal immunity and ultimately impacts respiratory health. Furthermore, we discuss how the microbiome affects mucosal immunity, considering tissue-specific variations, and its capacity in respiratory diseases containing asthma, chronic obstructive pulmonary disease, and lung cancer. Additionally, we investigate the external factors which affect the relationship between respiratory microbiome and mucosal immune responses. By exploring these intricate interactions, this review provides valuable insights into the potential for microbiome-based interventions to modulate mucosal immunity and alleviate the severity of respiratory diseases.
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Colorectal cancer (CRC) is the second-highest cause of cancer-associated mortality among both men and women worldwide. One of the risk factors for CRC is obesity, which is correlated with a high-fat diet prevalent in Western dietary habits. The association between an obesogenic high-fat diet and CRC has been established for several decades; however, the mechanisms by which a high-fat diet increases the risk of CRC remain unclear. Recent studies indicate that gut microbiota strongly infuence the pathogenesis of both high-fat diet-induced obesity and CRC. The gut microbiota is composed of hundreds of bacterial species, some of which are implicated in CRC. In particular, the expansion of facultative anaerobic Enterobacteriaceae, which is considered a microbial signature of intestinal microbiota functional imbalance (dysbiosis), is associated with both high-fat diet-induced obesity and CRC. Here, we review the interaction between the gut microbiome and its metabolic byproducts in the context of colorectal cancer (CRC) during high-fat diet-induced obesity. In addition, we will cover how a high-fat diet can drive the expansion of genotoxin-producing Escherichia coli by altering intestinal epithelial cell metabolism during gut infammation conditions.
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Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that can infect humans in contact with infected pigs
or their byproducts. It can employ different types of genes to defend against oxidative stress and ensure its survival. The
thioredoxin (Trx) system is a key antioxidant system that contributes adversity adaptation and pathogenicity. SS2 has been
shown to encode putative thioredoxin genes, but the biological roles, coding sequence, and underlying mechanisms remains
uncharacterized. Here, we demonstrated that SSU05_0237-ORF, from a clinical SS2 strain, ZJ081101, encodes a protein
of 104 amino acids with a canonical CGPC active motif and an identity 70–85% similar to the thioredoxin A (TrxA) in
other microorganisms. Recombinant TrxA efficiently catalyzed the thiol-disulfide oxidoreduction of insulin. The deletion
of TrxA led to a significantly slow growth and markedly compromised tolerance of the pathogen to temperature stress,
as well as impaired adhesion ability to pig intestinal epithelial cells (IPEC-J2). However, it was not involved in H2O2
and
paraquat-induced oxidative stress. Compared with the wild-type strain, the ΔTrxA strain was more susceptible to killing by
macrophages through increasing NO production. Treatment with TrxA mutant strain also significantly attenuated cytotoxic
effects on RAW 264.7 cells by inhibiting inflammatory response and apoptosis. Knockdown of pentraxin 3 in RAW 264.7
cells was more vulnerable to phagocytic activity, and TrxA promoted SS2 survival in phagocytic cells depending on pentraxin
3 activity compared with the wild-type strain. Moreover, a co-inoculation experiment in mice revealed that TrxA mutant
strain is far more easily cleared from the body than the wild type strain in the period from 8–24 h, and exhibits significantly
attenuated oxidative stress and liver injury. In summary, we reveal the important role of TrxA in the pathogenesis of SS2.
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Thioredoxin C of Streptococcus suis serotype 2 contributes to virulence by inducing antioxidative stress and inhibiting autophagy via the MSR1/PI3K-Akt-mTOR pathway in macrophages Chunxiao Ji, Yanying Pan, Bocheng Liu, Jianying Liu, Chijun Zhao, Zhuyuan Nie, Simeng Liao, Guangwei Kuang, Xin Wu, Quan Liu, Jie Ning, Yulong Tang, Lihua Fang Veterinary Microbiology.2024; 298: 110263. CrossRef
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Streptococcus suis type 2 (S. suis type 2, SS2), an infectious
pathogen which is zoonotic and can induce severely public
health concern. Our previous research identified a newly differential
secreted effector of tagatose-bisphosphate aldolase
(LacD) mediated by VirD4 factor within the putative type IV
secretion system of SS2, whereas the functional basis and roles
in virulence of LacD remain elusive. Here in this study, the
LacD was found enzymatic and can be activated to express
under oxidative stress. Gene mutant and its complemental
strain (ΔlacD and cΔlacD) were constructed to analyze the
phenotypes, virulence and transcriptomic profiles as compared
with the parental strain. The lacD gene deletion showed
no effect on growth capability and cells morphology of SS2.
However, reduced tolerance to oxidative and heat stress conditions,
increased antimicrobial susceptibility to ciprofloxacin
and kanamycin were found in ΔlacD strain. Further, the LacD
deficiency led to weakened invasion and attenuated virulence
since an easier phagocytosed and more prone to be cleared of
SS2 in macrophages were shown in ΔlacD mutant. Distinctive
transcriptional profiling in ΔlacD strain and typical downregulated
genes with significant mRNA changes including
alcohol dehydrogenase, GTPase, integrative and conjugative
elements, and iron ABC transporters which were mainly involved
in cell division, stress response, antimicrobial susceptibility
and virulence regulation, were examined and confirmed
by RNA sequencing and real time qPCR. In summary, the results demonstrated for the first time that LacD was a pluripotent
protein mediated the metabolic, stress and virulent
effect of SS2.
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In recent years, the occurrence of antibiotic-resistant pathogens
is increasing rapidly. There is growing concern as
the development of antibiotics is slower than the increase in
the resistance of pathogenic bacteria. Antimicrobial peptides
(AMPs) are promising alternatives to antibiotics. Despite their
name, which implies their antimicrobial activity, AMPs have
recently been rediscovered as compounds having antifungal,
antiviral, anticancer, antioxidant, and insecticidal effects.
Moreover, many AMPs are relatively safe from toxic side effects
and the generation of resistant microorganisms due to
their target specificity and complexity of the mechanisms underlying
their action. In this review, we summarize the history,
classification, and mechanisms of action of AMPs, and
provide descriptions of AMPs undergoing clinical trials. We
also discuss the obstacles associated with the development of
AMPs as therapeutic agents and recent strategies formulated
to circumvent these obstacles.
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Cryptococcus neoformans is an opportunistic fungal pathogen
causing cryptococcal meningoencephalitis. Interestingly,
the cell wall of C. neoformans contains chitosan, which is critical
for its virulence and persistence in the mammalian host.
C. neoformans (H99) has three chitin deacetylases (CDAs),
which convert chitin to chitosan. Herein, the classification
of the chitin-related protein (CRP) family focused on cryptococcal
CDAs was analyzed by phylogenetics, evolutionary
pressure (dN/dS), and 3D modeling. A phylogenetic tree of
110 CRPs revealed that they can be divided into two clades,
CRP I and II with bootstrap values (> 99%). CRP I clade comprises
five groups (Groups 1–5) with a total of 20 genes, while
CRP II clade comprises sixteen groups (Groups 6–21) with
a total of 90 genes. CRP I comprises only fungal CDAs, including
all three C. neoformans CDAs, whereas CRP II comprises
diverse CDAs from fungi, bacteria, and amoeba, along
with other carbohydrate esterase 4 family proteins. All CDAs
have the signal peptide, except those from group 11. Notably,
CDAs with the putative O-glycosylation site possess either the
glycosylphosphatidylinositol (GPI)-anchor motif for CRP I
or the chitin-binding domain (CBD) for CRP II, respectively.
This evolutionary conservation strongly indicates that the
O-glycosylation modification and the presence of either the
GPI-anchor motif or the chitin-binding domain is important
for fungal CDAs to function efficiently at the cell surface.
This study reveals that C. neoformans CDAs carrying GPI
anchors have evolved divergently from fungal and bacterial
CDAs, providing new insights into evolution and classification
of CRP family.
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Inflammatory bowel disease (IBD) is a result of chronic inflammation
caused, in some part, by dysbiosis of intestinal
microbiota, mainly commensal bacteria. Gut dysbiosis can
be caused by multiple factors, including abnormal immune
responses which might be related to genetic susceptibility,
infection, western dietary habits, and administration of antibiotics.
Consequently, the disease itself is characterized as
having multiple causes, etiologies, and severities. Recent studies
have identified > 200 IBD risk loci in the host. It has been
postulated that gut microbiota interact with these risk loci result ing in dysbiosis, and this subsequently leads to the development
of IBD. Typical gut microbiota in IBD patients
are characterized with decrease in species richness and many
of the commensal, and beneficial, fecal bacteria such as Firmicutes
and Bacteroidetes and an increase or bloom of Proteobacteria.
However, at this time, cause and effect relationships
have not been rigorously established. While treatments
of IBD usually includes medications such as corticosteroids,
5-aminosalicylates, antibiotics, immunomodulators, and anti-
TNF agents, restoration of gut dysbiosis seems to be a safer
and more sustainable approach. Bacteriotherapies (now called
microbiota therapies) and dietary interventions are effective
way to modulate gut microbiota. In this review, we summarize
factors involved in IBD and studies attempted to treat IBD
with probiotics. We also discuss the potential use of microbiota
therapies as one promising approach in treating IBD.
As therapies based on the modulation of gut microbiota becomes
more common, future studies should include individual
gut microbiota differences to develop personalized therapy
for IBD.
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It is increasingly evident that bidirectional interactions exist
among the gastrointestinal tract, the enteric nervous system,
and the central nervous system. Recent preclinical and clinical
trials have shown that gut microbiota plays an important role
in these gut-brain interactions. Furthermore, alterations in gut
microbiota composition may be associated with pathogenesis
of various neurological disorders, including stress, autism, depression,
Parkinson’s disease, and Alzheimer’s disease. Therefore,
the concepts of the microbiota-gut-brain axis is emerging.
Here, we review the role of gut microbiota in bidirectional
interactions between the gut and the brain, including
neural, immune-mediated, and metabolic mechanisms. We
highlight recent advances in the understanding of probiotic
modulation of neurological and neuropsychiatric disorders
via the gut-brain axis.
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The intestinal microbiota is comprised of millions of microorganisms
that reside in the gastrointestinal tract and consistently
interact with the host. Host factors such as diet and
disease status affect the composition of the microbiota, while
the microbiota itself produces metabolites that can further
manipulate host physiology. Dysbiosis of the intestinal microbiota
has been characterized in patients with certain metabolic
diseases, some of which involve damage to the host
intestinal epithelial barrier and alterations in the immune
system. In this review, we will discuss the consequences of dietdependent
bacterial dysbiosis in the gastrointestinal tract, and
how the associated interaction with epithelial and immune
cells impacts metabolic diseases.
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