Gut Microbiome Modulatory Potential Of Quorum Sensing Molecules Sakshi sharma (M.Sc. Graduate) Sharmasakshi2306@gmail.com Abstract Mammalian gut harbors a complex and very diverse microbial community. A healthy individual has unique and balanced gut microbiome which helps its host maintaining optimal health. unbalanced gut microbiome consortium lead to many disorders. Quorum sensing (QS) is a phenomenon thought to contribute shaping multispecies consortium via chemical signaling. In this review we aim to understand how QS affects microbial consortium in gut. as it’s important to understand that how multispecies interact with each other and how they synchronize their functions .by studying researches, it appears that Qs is used by organisms in many ways. Like pathogens use QS as a tool for virulence (8), on other hand QS signaling molecules are used for reestablishing homeostasis by favoring functional gut microflora (5), in addition it protects pathogen colonization by allowing residential organism to exhibit colonization resistance (8). also, QS helps organisms to survive in harsh conditions of mammalian gastrointestinal system (4). Beside the fact that gut microbiome is a very complex and many factors do contribute shaping it, We can say QS system do aid to give rise to a healthy gut microbiome.
Introduction
Figure 1: What is Quorum sensing Bacterial cell divides and achieve high density
Transcription
Lux boxes
Autoinducer AHL produced upon higher cell density by activity of LuxI gene.
Disease
A typical Mammalian gut is densely populated with thousands of different bacterial species. These commensals help by providing nutrition, preventing pathogen colonization and immune system development (4). among them 2 groups are abundant i.e. firmicutes and Bacteroidetes. homeostatic balance of gut microbiome is favorable for host. But often disruption of this balance(dysbiosis) occur and its potential reason are use of antibiotics, stress, type to diets etc. dysbiosis is a possible cause of many gastrointestinal disorders and others major diseases as shown in table 1. Equilibrium of gut flora relies on cell to cell communication via chemical signaling named Quorum sensing . Qs allows bacterial population to behave in a synchronized manner as It can regulate their collective behaviors like virulence, biofilm production, and drug resistance. As shown in figure 1., organisms do interspecies communication by autoinducers, mostly via acyl homoserine lactones (AHL’s). these signaling molecules are sensed and coupled with cytoplasmic DNA-binding transcriptional regulator (LuxR). AHL/LuxR dimer regulates gene expression related to virulence factor. In gut environment.
Research Use of antibiotics is a common root for unbalanced gut microbiome. It not only reduces pathogens but cause significant damage to commensal microbiota. Many researches sowed that QS molecules play a major role in reconstruction of healthy gut microbiome by releasing vast array of signaling molecules (1, 4).
LuxI couple to its cytoplasmic receptor LuxR and make LuxI/LuxR complex.
Alzheimer’s Autism Spectrum Disorders colorectal cancer
Crohn’s disease
Diabetes Mellitus Inflammatory bowel disease Obesity
Gene for biofilm, toxin, anti microbial resistance, pigments, etc.
LuxR is a DNA-binding transcriptional regulator , upon forming LuxI/R complex its C-terminal binds to DNA and regulate transcription of gene related to virulence in bacteria.
dysbiosis Decrease in E. Rectale Firmicutes, Bfidobacteria and Prevotella
Increase in Escherichia/Shigella Bacteroidetes, Clostridiales (Toxin of pathogen restrict development ) Proteobacteria, Bfidobacteria, Proteobacteria, Bfidobacteria, Prevotella Prevotella, firmicutes and Fusobacteria Bifidobacterium, Faecalibacterium Enterobacteriaceae family prausnitzii adolescentis, Dialister Ruminococcus gnavus invisu and clostridium cluster Mucin degrading bacteria Bacteroidetes and Clostridium Bacteroidetes, firmicutes and pathogenic bacteria Clostridium commensal microbiota. difficile, Mycobacterium avium Bacteroidetes firmicutes
Table 1: Comparisons between healthy individuals and diseased persons shows evident change in gut microbiome composition .table shows dysbiosis of gut microbiome in particular diseased condition (2,3). E. coli secreting AI-2
Bacteroidetes firmicutes
AI_2
Vibrio cholerae
(A).
When R. obeum is not present there is Low level of AI-2 which helps colonizing V. cholerae
Microbiome
Epithelial lining
(B).
When R. obeum is present in vicinity of V. cholerae it secretes more AI-2 and expands its population and thus inhibit pathogen colonizing.
Vibrio cholerae R.obeum
• To cause disease Vibrio cholerae use QS for colonizing and controlling virulence factor (8). • Metagenomic Comparison between healthy and diseased person showed that recovery process is accomplished by assembly of a specific taxa. • Further metatranscriptomics studies showed that, Ruminococcus obeum, gives protection against V. cholerae, by causing colonization resistance.
• When R. obeum senses V. cholerae in vicinity it tend to secretes more of Microbiome autoinducer via a gene homologue to LuxS (LuxS involved in AI-2 production). R. obeum increase in no by QS and cause colonization resistance for V. cholera. (8) • Gamma proteobacteria family member like Escherichia coli, salmonella enterica, Klebsiella pneumoniae, and Enterobacter encode AHL receptor homologue named SdiA, but they don’t encode their own AHL’s. • via SdiA Escherichia coli (EHEC) O157:H7 sense AHL produced in bovine rumen environment. This QS system helps encoding acid resistance gene making E.coli to populate in acidic environment (7). Host originated Catecholamine like, epinephrine (E), norepinephrine (NE) and dopamine can be found in gut for proper functioning of gut motility, K/Cl secretion, inflammation etc. E. coli and Salmonella enterica do sense and respond them by using two component system consisting a histidine sensor kinase and its cognate response regulator. E is detected by QseC histidine kinase of QseC/B signalling system while NE is sensed by QseE histidine kinase of QseE/F. Upon phosphorylation QseC and QseE relay
AI2
Streptomycin treatment
Use of streptomycin brings fall in Firmicutes to Bacteroidetes ratio. Firmicutes, who perform important functions in gut are greatly decreased.
E.coli producing more AI-2 introduced
Author aimed to understand role of QS, streptomycin treated mice was colonized with genetically altered E. coli capable of producing more Autoinducer-2 (AI2) signalling molecule.
results showed that AI-2 not only give rise to a different composition of gut flora but actually favours firmicutes to repopulate (5).
information via a phosphorylation event to QseB and QseF respectively. QseB and QseF transcriptional regulator then controls gene expression for flagellar motion, virulence, and motility (4). QseC seems to be essential for in vivo colonization, for E. coli, Salmonella enterica and , Citrobacter rodentium. catecholamine sensor QseC is also able to sense QS molecule Autoinducer-3(AI-3) secreted by human intestinal microbiota (4). Qse E
Qse C
Epinephrin
E
Qse B
Norepinephrin Bacterial membrane
p
p p
N E
Qse B
Qse F
p
Qse F
controls gene expression for flagellar motion, virulence, and motility.
Conclusion Quorum sensing is process of chemical signaling that exerts different consequences on different organisms in gut environment. Collectively these different outcome shapes a balanced gut microbiome. Here we understood importance of AI-2 which is a widely used signaling molecule among different species. while not much knowledge is their about AI-3 which can be a game changer in course of shaping gut microbiome(4). AI-2 turns out a successful signaling molecule assist in reestablishment of healthy gut microbiome after use of antimicrobials. Gut microbiome is expected to having crosstalk with host which is seen in the case of Catecholamine signalling. This review gives a little sight on how QS can work in gut microbiome , however much more facts are yet to be known to understand gut microbiome functionality .
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