Differences in the effects and action modes of gut commensals against dextran sulfate sodium-induced intestinal inflammation

Inflammatory bowel disease(IBD)is a complex relapsing inflammatory disease in the gut and is driven by complicated host-gut microbiome interactions.Gut commensals have shown different functions in IBD prevention and treatment.To gain a mechanistic understanding of how different commensals affect intestinal inflammation,we compared the protective effects of 6 probiotics(belonging to the genera Akkermansia,Bifidobacterium,Clostridium,and Enterococcus)on dextran sulfate sodium(DSS)-induced colitis in mice with or without gut microbiota.Anti-inflammatory properties(ratio of interleukin(IL)-10 and IL-12)of these strains were also evaluated in an in vitro mesenteric lymph nodes(MLN)co-culture system.Results showed that 4 probiotics(belonging to the species Bifidobacterium breve,Bifidobacterium bifidum,and Enterococcus faecalis)can alleviate colitis in normal mice.The probiotic strains differed in regulating the intestinal microbiota,cytokines(IL-10,IL-1βand interferon(IFN)-γ),and tight junction function(Zonulin-1 and Occludin).By constrast,Akkermansia muciniphila AH39 and Clostridium butyricum FHuNHHMY49T1 were not protective.Interestingly,B.breve JSNJJNM2 with high anti-inflammatory potential in the MLN model could relieve colitis symptoms in antibiotic cocktail(Abx)-treated mice.Meanwhile,E.faecalis FJSWX25M1induced low levels of cytokines in vitro and showed no beneficial effects.Therefore,we provided insight into the clinical application of probiotics in IBD treatment.

Helicobacter pylori:Commensal,symbiont or pathogen?

This review considers the data on Helicobacter pylori(H.pylori),which have been accumulated over 40 years since its description as an etiological factor in gastrointestinal diseases.The majority of modern publications are devoted to the study of the pathogenic properties of the microorganism in the development of chronic gastritis,peptic ulcer disease,and gastric cancer,as well as methods for its eradication.However,in recent years,there have been more and more studies which have suggested that H.pylori has a beneficial,or potentially positive,effect on the human body.The authors have attempted to objectively analyze the information accumulated in the literature on H.pylori.Some studies consider it as one of the recently identified human bacterial pathogens,and special attention is paid to the evidence suggesting that it is probably part of the composition of the human microbiome as a commensal(commensal from French to English is a table companion)or even a symbiont.The presented data discussing the presence or absence of the effect of H.pylori on human health suggest that there is an apparent ambiguity of the problem.The re-assessment of the data available on H.pylori infection is important in order to answer the question of whether it is necessary to create a program of mass H.pylori eradication or to apply a more personalized approach to treating patients with H.pylori-associated gastrointestinal diseases and to perform eradication therapy.

Different cytokine response of primary colonic epithelial cells to commensal bacteria

AIM: To determine if primary murine colonic epithelial cells (CEC) respond to commensal bacteria and discriminate between different types of bacteria. METHODS: A novel CEC: bacteria co-culture system was used to compare the ability of the colonic commensal bacteria, Bacteroides ovatus, E coli(SLF) and Lactobacillus rhamnosus (LGG) to modulate production of different cytokines (n = 15) by primary CEC. Antibody staining and flow cytometry were used to investigate Toll-like receptor (TLR) expression by CEC directly ex vivo and TLR responsiveness was determined by examining the ability of TLR ligands to influence CEC cytokine production. RESULTS: Primary CEC constitutively expressed functional TLR2 and TLR4. Cultured in complete medium alone, CEC secreted IL-6, MCP-1 and IP-10 the levels of which were significantly increased upon addition of the TLR ligands peptidoglycan (PGN) and lipopolysaccharide (LPS). Exposure to the commensal bacteria induced or up-regulated different patterns of cytokine production and secretion.E coli induced production of MIP-1α/β and p defensin3 whereas B. ovatus and L. rhamnosus exclusively induced MCP-1 and MIP-2α expression, respectively. TNFa, RANTES and MEC were induced or up-regulated in response to some but not all of the bacteria whereas ENA78 and IP-10 were up-regulated in response to all bacteria. Evidence of bacterial interference and suppression of cytokine production was obtained from mixed bacterial: CEC co-cultures. Probiotic LGG suppressed E coli- and B. ovatus-induced cytokine mRNA accumulation and protein secretion. CONCLUSION: These observations demonstrate the ability of primary CEC to respond to and discriminate between different strains of commensal bacteria and identify a mechanism by which probiotic bacteria (LGG) may exert anti-inflammatory effects in vivo.

The oral commensal Streptococcus mitis activates the aryl hydrocarbon receptor in human oral epithelial cells

Streptococcus mitis （S. mitis） is a pioneer commensal bacterial species colonizing many of the surfaces of the oral cavity in healthy individuals. Yet, not much information is available regarding its interaction with the host. We used examination of its transcriptional regulation in oral keratinocytes to elucidate some of its potential roles in the oral cavity. Transcription factor analysis of oral keratinocytes predicted S. mitis.mediated activation of aryl hydrocarbon receptor （AhR）, Activation and functionality of AhR was confirmed through nuclear translocation determined by immunofluorescence microscopy and real-time polymerase chain reaction with reverse transcription analysis of CYPIA1, the hallmark gene for AhR activation. Addition of Streptococcus mutans or Streptococcus gordonfi did not induce CYPIA1 transcription in the keratinocyte cultures. Introduction of an AhR-specific inhibitor revealed that S. mitis-mediated transcription of CXCL2 and CXCL8 was regulated by AhR. Elevated levels of pmstaglandin E2 （enzyme-linked immunosorbent assay） in supernatants from S. mitis-treated oral epithelial cells were also attenuated by inhibition of AhR activity. The observed AhR-regulated activities point to a contribution of S. mitis in the regulation of inflammatory responses and thereby to wound healing in the oral cavity. The concept that the oral commensal microbiota can induce AhR activation is important, also in view of the role that AhR has in modulation of T-cell differentiation and as an anti-inflammatory factor in macrophaees.

Production of corticotropin-releasing factor and urocortin from human monocyte-derived dendritic cells is stimulated by commensal bacteria in intestine

AIM: To examine whether commensal bacteria are a contributing cause of stress-related mucosal inflammation.

Commensal Oral Candida in Asian Cohorts

Samaranayake L. Commensal Oral Candida in Asian Cohorts. International Journal of Oral Science, 1 （1）： 2-5, 2009The oral carriage rate of Candida in healthy humans ranges from 40% to 60%. However for a prolonged period, the oral candidal prevalence in humans was documented essentially using data from studies in the West as their prevalence in inhabitants in different regions of the world,including Asia was not known. Yet, recent reports from a number of studies indicate the quality, quantity and prevalence of oral yeasts differ between Asia and other regions for reason that are still unclear. This mini review on such data from Asian studies on oral carriage of Candida provides another intriguing facet of the behavior of this ubiquitous yeast.

The commensal consortium of the gut microbiome is associated with favorable responses to anti-programmed death protein 1 (PD-1) therapy in thoracic neoplasms

Objective:Immune checkpoint inhibitors have revolutionized cancer therapy for multiple types of solid tumors,but as expected,a large percentage of patients do not show durable responses.Biomarkers that can predict clinical responses to immunotherapies at diagnosis are therefore urgently needed.Herein,we determined the associations between baseline gut commensal microbes and the clinical treatment efficiencies of patients with thoracic neoplasms during anti-programmed death protein 1(PD-1)therapy.Methods:Forty-two patients with advanced thoracic carcinoma who received anti-PD-1 treatment were enrolled in the study.Baseline and time-serial stool samples were analyzed using 16S ribosomal RNA gene sequencing.Tumor responses,patient progression-free survival,and overall survival were used to measure clinical outcomes.Results:The diversities of the baseline gut microbiota were similar between responders(n=23)and nonresponders(n=19).The relative abundances of the Akkermansiaceae,Enterococcaceae,Enterobacteriaceae,Carnobacteriaceae and Clostridiales Family XI bacterial families were significantly higher in the responder group.These 5 bacterial families acted as a commensal consortium and better stratified patients according to clinical responses(P=0.014).Patients with a higher abundance of commensal microbes had prolonged PFS(P=0.00016).Using multivariable analysis,the abundance of the commensal consortium was identified as an independent predictor of anti-PD-1 immunotherapy in thoracic neoplasms(hazard ratio:0.17;95%confidence interval:0.05–0.55;P=0.003).Conclusions:Baseline gut microbiota may have a critical impact on anti-PD-1 treatment in thoracic neoplasms.The abundance of gut commensal microbes at diagnosis might be useful for the early prediction of anti-PD-1 immunotherapy responses.

Corticotropin-releasing factor secretion from dendritic cells stimulated by commensal bacteria

AIM:To study the production and secretion of corticotropin-releasing factor (CRF) by dendritic cells and the influence of commensal bacteria.METHODS:JAWSⅡ cells (ATCC CRL-11904),a mouse dendritic cell line,were seeded into 24-well culture plates and grown for 3 d.Commensal bacterial strains of Clostridium clostrodiiforme (JCM1291),Bacteroides vulgatus (B.vulgatus) (JCM5856),Escherichia coli (JCM1649),or Fusobacterium varium (F.varium) (ATCC8501) were added to the cells except for the control well,and incubated for 2 h.After incubation,we performed enzyme-linked immunosorbent assay for the cultured medium and reverse transcription polymerase chain reaction for the dendritic cells,and compared these values with controls.RESULTS:The level of CRF secretion by control dendritic cells was 40.4±6.2 pg/mL.The CRF levels for cells incubated with F.varium and B.vulgatus were significantly higher than that of the control (P<0.0001).CRF mRNA was present in the control sample without bacteria,and CRF mRNA levels in all samples treated with bacteria were above that of the control sample.F.varium caused the greatest increase in CRF mRNA expression.CONCLUSION:Our results suggest that dendritic cells produce CRF,a process augmented by commensal bacteria.

Alentiana palinpoda,a new commensal polynoid species from a seamount in the Northwest Pacific Ocean

Alentiana has only one member,A.aurantiaca(Verrill,1885),commensal with sea anemone(Bolocera tuediae).Here,Alentiana palinpoda sp.nov.,a second member in the genus Alentiana(subfamily Lepidastheniinae),a new commensal polynoid is described,based on a specimen collected from a deep-water seamount in the Northwest Pacific Ocean.The new species is characterized by large elytra that completely cover the dorsum and are present in every third segment in the posterior regions.Neuropodia are truncated,with two types of neurochaetae;supraacicular chaetae toothed on one side with a slightly inflated end,and subacicular chaetae that are heavy and smooth;the prechaetal lobe is larger than the postchaetal lobe,with the ventral part rolling upward and backward.

The Composition of Colonic Commensal Bacteria According to Anatomical Localization in Colorectal Cancer

Colorectal cancer （CRC） is a multistage disease resulting from complex factors, including genetic mutations, epigenetic changes, chronic inflammation, diet, and lifestyle. Recent accumulating evidence suggests that the gut microbiota is a new and important player in the development of CRC. Imbalance of the gut microbiota, especially dysregulated gut bacteria, contributes to colon cancer through mechanisms of inflammation, host defense modulations, oxidative stress, and alterations in bacterial-derived metabolism. Gut commensal bacteria are anatomically defined as four populations： luminal commensal bacteria, mucus-resident bacteria, epithelium-resident bacteria, and lymphoid tissue-resident commensal bacteria. The bacterial flora that are harbored in the gastrointestinal （GI） tract vary both longitudinally and cross-sectionally by different anatomical localization. It is notable that the translocation of colonic commensal bacteria is closely related to CRC progression. CRC-associated bacteria can serve as a noninvasive and accurate biomarker for CRC diagnosis. In this review, we summarize recent findings on the oncogenic roles of gut bacteria with different anatomical localization in CRC progression.

Gut commensal bacteria, Paneth cells and their relations to radiation enteropathy

In steady state, the intestinal epithelium forms an important part of the gut barrier to defend against luminal bacterial attack. However, the intestinal epithelium is compromised by ionizing irradiation due to its inherent selfrenewing capacity. In this process, small intestinal bacterial overgrowth is a critical event that reciprocally alters the immune milieu. In other words, intestinal bacterial dysbiosis induces inflammation in response to intestinal injuries, thus influencing the repair process of irradiated lesions. In fact, it is accepted that commensal bacteria can generally enhance the host radiation sensitivity. To address the determination of radiation sensitivity, we hypothesize that Paneth cells press a critical "button" because these cells are central to intestinal health and disease by using their peptides, which are responsible for controlling stem cell development in the small intestine and luminal bacterial diversity. Herein,the most important question is whether Paneth cells alter their secretion profiles in the situation of ionizing irradiation. On this basis, the tolerance of Paneth cells to ionizing radiation and related mechanisms by which radiation affects Paneth cell survival and death will be discussed in this review. We hope that the relevant results will be helpful in developing new approaches against radiation enteropathy.

Effect of Using Mouthwash Solution on Commensal Flora of the Oral Cavity among Female Students in Qassim University

Oral health is the pathway to one’s general health and wellness. Mouthwash is a product used as an adjunct to oral hygiene practices as an antiseptic and antiplaque and antimicrobial agent. The awareness of using mouthwash solution is so limited worldwide. And maybe there’s effect of mouthwash on commensal flora. The aim of this study is to measure the effect of using Mouthwash solution on commensal flora of the oral cavity. In this study, we determined three groups, the first group is considered as a basic group where Female students are not using any mouthwash, the second group used mouthwash twice daily for two weeks, group number three used mouthwash twice weekly. We take cytological sample scraping from oral cavity. All the cytological sections of all groups stained with Papanicolaou stain and examined the slides under the microscope. The study came out with the following results: The basic group that did not use any mouthwash remained unchanged, while the second group, who used mouthwash twice daily, showed a clear epithelial tissue for any bacteria and a clear background. Group number three, who used mouthwash twice a week, showed countable bacteria in epithelial tissue with a clear background. Finally, the study concluded: Cosmetic mouthwash solution has a bad effect on commensal flora if you over used it and leads to killing all your normal flora in oral cavity as much as therapeutic mouthwash will do.

Lattice and Lattice Gas Models for Commensalism: Two Shellfishes in Intertidal Zone

The study of mutual interactions in an intertidal zone is important. We are interested in two sessile shellfishes, mussel (Septifer virgatus: species X) and goose barnacle (Capitulum mitella: species Y). Both species X and Y have similar body sizes, and live in an intertidal zone. Their relation is known to be a kind of commensalism: the survival rate of X increases near the location of Y. In contrast, Y receives no gain from X. In the present paper, we present lattice and lattice gas models for commensalism. The latter is mean-field theory of the former. It is found that the relation of commensalism is not stable. Under certain conditions, the competition prevails between both species;if the density of Y is high, the species X receives a damage originated in the limiting space. Moreover, we find that the basic equation derived by lattice gas model well explains the population dynamics for lattice model.

Commensal <i>E. Coli</i>Strains Uniquely Alter the ECM Topography Independent of Colonic Epithelial Cells

The relationship between commensal bacteria and the epithelial cells lining the colon is normally symbiotic. However, in the setting of diseases which lead to a loss of the protective mucosal layer such as inflammatory bowel disease or colon cancer, commensal bacteria gain the ability to alter both the behavior of epithelial cells as well as their surrounding extra cellular matrix (ECM). While much work has been done to understand the effects of bacteria on diseased epithelial cells in the colon, very little has been done to understand their impact on the ECM. In our previous work, we have shown that topographical changes in the ECM on the luminal side of the colon have a profound influence on the behavior of colonic epithelial cells. However, we do not understand all of the mechanisms that lead to changes in the ECM topography. This study aimed to understand the role that commensal E. coli strains play in altering the ECM topography of type-1 collagen scaffolds. To do this, 1.2 mg/ml type 1 collagen scaffolds were infected with various commensal bacterial strains. At 24 hours post-infection collagen fiber dimensions and substrate topography were determined using standard molecular biology techniques and advanced imaging. Intriguingly, all of the commensal E. coli strains showed some form of substrate degradation. Especially in the case of commensal E. coli strain HS4, maximum nano-scaled protrusions were observed. This data suggests, for the first time, that studying the effects of bacteria alone on the ECM may be critical to improving our understanding of how the cellular microenvironment changes in both health and disease.

Physiological strategies in wild rodents:immune defenses of commensal rats

The importance of issues associated with urban/commensal rats and mice(property damage,management costs,and health risks)press upon research on these animals.While the demography of commensal rodents is mostly studied,the need for understanding factors influencing their natural morbidity/mortality is also stressed.In this respect,more attention is expected to be paid to immunity,the physiological mechanism of defense against host survival threats(pathogens,parasites,diseases).Commensal rats and mice carry numerous pathogens that evoke diverse immune responses.The state of immunity in commensal house mice is studied in great detail,owing to the use of laboratory strains in biomedical research.Because commensal rats are,compared to mice,carriers of more zoonotic agents,rats’immunity is studied mainly in that context.Some of these zoonotic agents cause chronic,asymptomatic infections,which justified studies of immunological mechanisms of pathogen tolerance versus clearance regulation in rats.Occurrence of some infections in specific tissues/organs pressed upon analysis of local/regional immune responses and/or immunopathology.A survey of immunological activity/responses in commensal rats is given in this review,with mention of existing data in commensal mice.It should throw some light on the factors relevant to their morbidity and lifespan,supplementing the knowledge of commensal rodent ecology.

An expanding stage for commensal microbes in host immune regulation

Gastrointestinal commensal microbiota is a concentrated mix of microbial life forms, including bacteria, fungi, archaea and viruses. These life forms are targets of host antimicrobial defense in order to establish a homeostatic symbiosis inside the host. However, they are also instrumental in shaping the functions of our immune system via a diverse set of communication mechanisms. In the gut, T helper 17, regulatory T and B cells are continuously tuned by specific microbial strains and metabolic processes. These cells in return help to establish a mutually beneficial exchange with the gut microbial contents. Imbalances in this symbiosis lead to dysregulations in the host＇s ability to control infections and the development of autoimmune diseases. In addition, the commensal microbiota has a significant and obligatory role in shaping both gut intrinsic and distal lymphoid organs, casting a large impact on the overall immune landscape in the host. This review discusses the major components of the microbial community in the gut and how its members collectively and individually exert regulatory roles in the host immune system and lymphoid structure development, as well as the functions of several major immune cell types.

Commensal Microbiome Promotes Resistance to Local and Systemic Infections

Objective：In this review,to illustrate the resistance mechanism for pathogen insult,we discussed the role of the intestinal microbiome in promoting resistance to local gastrointestinal tract infections and to respiratory tract infections.Data Sources：The review was based on data obtained from the published research articles.Study Selection：A total of 49 original articles were selected in accordance with our main objective to illustrate the resistance mechanism（s） by which commensal microbiota can contribute to host defense against local and systemic infections.Results：Diverse microorganisms colonize human environmentally exposed surfaces such as skin,respiratory tract,and gastrointestinal tract.Co-evolution has resulted in these microbes with extensive and diverse impacts on multiple aspects of host biological functions.During the last decade,high-throughput sequencing technology developed has been applied to study commensal microbiota and their impact on host biological functions.By using pathogen recognition receptors pathway and nucleotide binding oligomerization domain-like receptors pathway,the commensal microbiome promotes resistance to local and systemic infections,respectively.To protect against the local infections,the microbiome functions contain the following：the competing for sites of colonization,direct production of inhibition molecules or depletion of nutrients needed for pathogens,and priming immune defenses against pathogen insult.At the same time,with the purpose to maintain homeostasis,the commensal bacteria can program systemic signals toward not only local tissue but also distal tissue to modify their function for infections accordingly.Conclusions：Commensal bacteria play an essential role in protecting against infections,shaping and regulating immune responses,and maintaining host immune homeostasis.

Commensal microbiota and host metabolic divergence are associated with the adaptation of Diploderma vela to spatially heterogeneous environments

Heterogeneous environment adaptation is critical to understand the species evolution and response to climate change.However,how narrow-range species adapt to micro-geographic heterogeneity has been overlooked,and there is a lack of insights from metabolism and commensal microbiota.Here,we studied the environmental adaptation for 3 geographic populations(>40 km apart)of Diploderma vela,a lizard endemic to dry-hot valleys of the Hengduan Mountain Region.The climatic boundary caused a cooler,droughtier,and barren environment for northernmost population(RM)than the middle(QZK)and southernmost populations(FS).Correspondingly,significant divergences in liver and muscle metabolism and commensal microbiota were detected between RM and QZK or FS individuals,but not between QZK and FS individuals.Phospholipid composition,coenzyme level(i.e.pyridoxal and NAD^(+)),and cholesterol metabolism(e.g.androgen and estriol synthesis)constituted the major metabolic difference between RM and QZK/FS groups.FS and QZK individuals kept abundant Proteobacteria and antifungal strains,while RM individuals maintained more Firmicutes and Bacteroidota.Strong associations existed between varied host metabolite and gut microbes.How were these interpopulation variations associated to the environment adaptation were discussed.These results provided some novel insights into the environmental adaptation and implicated the consequence of climate change on narrow-range species.

Interactions between commensal bacteria and viral infection:insights for viral disease control in farmed animals

Viral diseases cause serious economic loss in farmed animals industry.However,the efficacy of remedies for viral infection in farmed animals is limited,and treatment strategies are generally lacking for aquatic animals.Interactions of commensal microbiota and viral infection have been studied in recent years,demonstrating a third player in the interaction between hosts and viruses.Here,we discuss recent developments in the research of interactions between commensal bacteria and viral infection,including both promotion and inhibition effect of commensal bacteria on viral pathogenesis,as well as the impact of viral infection on commensal microbiota.The antiviral effect of commensal bacteria is mostly achieved through priming or regulation of the host immune responses,involving differential microbial components and host signaling pathways,and gives rise to various antiviral probiotics.Moreover,we summarize studies related to the interaction between commensal bacteria and viral infection in farmed animals,including pigs,chickens,fish and invertebrate species.Further studies in this area will deepen our understanding of antiviral immunity of farmed animals in the context of commensal microbiota,and promote the development of novel strategies for treatment of viral diseases in farmed animals.

STABILITY ANALYSIS OF A LOTKA-VOLTERRA COMMENSAL SYMBIOSIS MODEL INVOLVING ALLEE EFFECT

In this paper, we present a stability analysis of a Lotka-Volterra commensal symbiosis model subject to Allee effect on the unaffected population which occurs at low population density. By analyzing the Jacobian matrix about the positive equilibrium, we show that the positive equilibrium is locally asymptotically stable. By applying the differential inequality theory, we show that the system is permanent, consequently, the boundary equilibria of the system is unstable. Finally, by using the Dulac criterion, we show that the positive equilibrium is globally stable. Although Allee effect has no influence on the final densities of the predator and prey species, numeric simulations show that the system subject to an Allee effect takes much longer time to reach its stable steady-state solution, in this sense that Allee effect has unstable effect on the system, however, such an effect is controllable. Such an finding is greatly different to that of the predator-prey model.