Interaction Between the Microbiota, Epithelia, and Immune Cells in the Intestine.

The gastrointestinal tract harbors numerous commensal bacteria, referred to as the microbiota, that benefit host health by digesting dietary components and eliminating pathogens. The intestinal microbiota maintains epithelial barrier integrity and shapes the mucosal immune system, balancing host defense and oral tolerance with microbial metabolites, components, and attachment to host cells. To avoid aberrant immune responses, epithelial cells segregate the intestinal microbiota from immune cells by constructing chemical and physical barriers, leading to the establishment of host-commensal mutualism. Furthermore, intestinal immune cells participate in the maintenance of a healthy microbiota community and reinforce epithelial barrier functions. Perturbations of the microbiota composition are commonly observed in patients with autoimmune diseases and chronic inflammatory disorders. An understanding of the intimate interactions between the intestinal microbiota, epithelial cells, and immune cells that are crucial for the maintenance of intestinal homeostasis might promote advances in diagnostic and therapeutic approaches for various diseases.

Mucosal Ecological Network of Epithelium and Immune Cells for Gut Homeostasis and Tissue Healing.

The intestinal epithelial barrier includes columnar epithelial, Paneth, goblet, enteroendocrine, and tuft cells as well as other cell populations, all of which contribute properties essential for gastrointestinal homeostasis. The intestinal mucosa is covered by mucin, which contains antimicrobial peptides and secretory IgA and prevents luminal bacteria, fungi, and viruses from stimulating intestinal immune responses. Conversely, the transport of luminal microorganisms-mediated by M, dendritic, and goblet cells-into intestinal tissues facilitates the harmonization of active and quiescent mucosal immune responses. The bacterial population within gut-associated lymphoid tissues creates the intratissue cohabitations for harmonized mucosal immunity. Intermolecular and intercellular communication among epithelial, immune, and mesenchymal cells creates an environment conducive for epithelial regeneration and mucosal healing. This review summarizes the so-called intestinal mucosal ecological network-the complex but vital molecular and cellular interactions of epithelial mesenchymal cells, immune cells, and commensal microbiota that achieve intestinal homeostasis, regeneration, and healing.

Long-term tolerance to skin commensals is established neonatally through a specialized dendritic cell subgroup.

Early-life establishment of tolerance to commensal bacteria at barrier surfaces carries enduring implications for immune health but remains poorly understood. Here, we showed that tolerance in skin was controlled by microbial interaction with a specialized subset of antigen-presenting cells. More particularly, CD301b+ type 2 conventional dendritic cells (DCs) in neonatal skin were specifically capable of uptake and presentation of commensal antigens for the generation of regulatory T (Treg) cells. CD301b+ DC2 were enriched for phagocytosis and maturation programs, while also expressing tolerogenic markers. In both human and murine skin, these signatures were reinforced by microbial uptake. In contrast to their adult counterparts or other early-life DC subsets, neonatal CD301b+ DC2 highly expressed the retinoic-acid-producing enzyme, RALDH2, the deletion of which limited commensal-specific Treg cell generation. Thus, synergistic interactions between bacteria and a specialized DC subset critically support early-life tolerance at the cutaneous interface.

Regulation of immune responses to food by commensal microbes.

The increasing prevalence of immune-mediated non-communicable chronic diseases, such as food allergies, has prompted a deeper investigation into the role of the gut microbiome in modulating immune responses. Here, we explore the complex interactions between commensal microbes and the host immune system, highlighting the critical role of gut bacteria in maintaining immune homeostasis. We examine how modern lifestyle practices and environmental factors have disrupted co-evolved host-microbe interactions and discuss how changes in microbiome composition impact epithelial barrier function, responses to food allergens, and susceptibility to allergic diseases. Finally, we examine the potential of bioengineered microbiome-based therapies, and live biotherapeutic products, for reestablishing immune homeostasis to prevent or treat food allergies.

Ingested soil bacteria breach gut epithelia and prime systemic immunity in an insect.

Insects lack acquired immunity and were thought to have no immune memory, but recent studies reported a phenomenon called immune priming, wherein sublethal dose of pathogens or nonpathogenic microbes stimulates immunity and prevents subsequential pathogen infection. Although the evidence for insect immune priming is accumulating, the underlying mechanisms are still unclear. The bean bug Riptortus pedestris acquires its gut microbiota from ambient soil and spatially structures them into a multispecies and variable community in the anterior midgut and a specific, monospecies Caballeronia symbiont population in the posterior region. We demonstrate that a particular Burkholderia strain colonizing the anterior midgut stimulates systemic immunity by penetrating gut epithelia and migrating into the hemolymph. The activated immunity, consisting of a humoral and a cellular response, had no negative effect on the host fitness, but on the contrary protected the insect from subsequent infection by pathogenic bacteria. Interruption of contact between the Burkholderia strain and epithelia of the gut weakened the host immunity back to preinfection levels and made the insects more vulnerable to microbial infection, demonstrating that persistent acquisition of environmental bacteria is important to maintain an efficient immunity.

An Ocular Commensal Protects against Corneal Infection by Driving an Interleukin-17 Response from Mucosal γδ T Cells.

Mucosal sites such as the intestine, oral cavity, nasopharynx, and vagina all have associated commensal flora. The surface of the eye is also a mucosal site, but proof of a living, resident ocular microbiome remains elusive. Here, we used a mouse model of ocular surface disease to reveal that commensals were present in the ocular mucosa and had functional immunological consequences. We isolated one such candidate commensal, Corynebacterium mastitidis, and showed that this organism elicited a commensal-specific interleukin-17 response from γδ T cells in the ocular mucosa that was central to local immunity. The commensal-specific response drove neutrophil recruitment and the release of antimicrobials into the tears and protected the eye from pathogenic Candida albicans or Pseudomonas aeruginosa infection. Our findings provide direct evidence that a resident commensal microbiome exists on the ocular surface and identify the cellular mechanisms underlying its effects on ocular immune homeostasis and host defense.

Pathogenesis of IgA nephropathy as a tissue-specific autoimmune disease.

Glomerulonephritis (GN) is a group of heterogeneous immune-mediated kidney diseases that causes inflammation within the glomerulus. Autoantibodies (auto-Abs) are considered to be central effectors in the pathogenesis of several types of GN. IgA nephropathy (IgAN) is the most common GN worldwide and is characterized by deposition of IgA in the glomerular mesangium of the kidneys, which is thought to be mediated by immune complexes containing non-specific IgA. However, we recently reported that IgA auto-Abs specific to mesangial cells (anti-mesangium IgA) were found in the sera of gddY mice, a spontaneous IgAN model, and patients with IgAN. We identified two autoantigens (ß2-spectrin and CBX3) that are selectively expressed on the mesangial cell surface and targeted by anti-mesangial IgA. Our findings redefined IgAN as a tissue-specific autoimmune disease. Regarding the mechanisms of production of anti-mesangium IgA, studies using gddY mice have revealed that production of anti-CBX3 IgA is induced by particular strains of commensal bacteria in the oral cavity, possibly through their molecular mimicry to CBX3. Here, we discuss a new concept of IgAN pathogenesis from the perspective of this disease as autoimmune GN caused by tissue-specific auto-Abs.

Lactobacillus crispatus Limits Bladder Uropathogenic E. coli Infection by Triggering a Host Type I Interferon Response.

Many urinary tract infections (UTIs) are recurrent because uropathogens persist within the bladder epithelial cells (BECs) for extended periods between bouts of infection. Because persistent uropathogens are intracellular, they are often refractive to antibiotic treatment. The recent discovery of endogenous Lactobacillus spp. in the bladders of healthy humans raised the question of whether these endogenous bacteria directly or indirectly impact intracellular bacterial burden in the bladder. Here, we report that in contrast to healthy women, female patients experiencing recurrent UTIs have a bladder population of Lactobacilli that is markedly reduced. Exposing infected human BECs to L. crispatus in vitro markedly reduced the intracellular uropathogenic Escherichia coli (UPEC) load. The adherence of Lactobacilli to BECs was found to result in increased type I interferon (IFN) production, which in turn enhanced the expression of cathepsin D within lysosomes harboring UPECs. This lysosomal cathepsin D-mediated UPEC killing was diminished in germ-free mice and type I IFN receptor-deficient mice. Secreted metabolites of L. crispatus seemed to be responsible for the increased expression of type I IFN in human BECs. Intravesicular administration of Lactobacilli into UPEC-infected murine bladders markedly reduced their intracellular bacterial load suggesting that components of the endogenous microflora can have therapeutic effects against UTIs.

Nutrient requirements shape the preferential habitat of Allorhizobium vitis VAR03-1, a commensal bacterium, in the rhizosphere of Arabidopsis thaliana.

A diverse range of commensal bacteria inhabit the rhizosphere, influencing host plant growth and responses to biotic and abiotic stresses. While root-released nutrients can define soil microbial habitats, the bacterial factors involved in plant-microbe interactions are not well characterized. In this study, we investigated the colonization patterns of two plant disease biocontrol agents, Allorhizobium vitis VAR03-1 and Pseudomonas protegens Cab57, in the rhizosphere of Arabidopsis thaliana using Murashige and Skoog (MS) agar medium. VAR03-1 formed colonies even at a distance from the roots, preferentially in the upper part, while Cab57 colonized only the root surface. The addition of sucrose to the agar medium resulted in excessive proliferation of VAR03-1, similar to its pattern without sucrose, whereas Cab57 formed colonies only near the root surface. Overgrowth of both bacterial strains upon nutrient supplementation inhibited host growth, independent of plant immune responses. This inhibition was reduced in the VAR03-1 ΔrecA mutant, which exhibited increased biofilm formation, suggesting that some activities associated with the free-living lifestyle rather than the sessile lifestyle may be detrimental to host growth. VAR03-1 grew in liquid MS medium with sucrose alone, while Cab57 required both sucrose and organic acids. Supplementation of sugars and organic acids allowed both bacterial strains to grow near and away from Arabidopsis roots in MS agar. These results suggest that nutrient requirements for bacterial growth may determine their growth habitats in the rhizosphere, with nutrients released in root exudates potentially acting as a limiting factor in harnessing microbiota.

Bacterial peptidoglycan signalling in microglia: Activation by MDP via the NF-κB/MAPK pathway.

Bacterial peptidoglycan (PGN) fragments are commonly studied in the context of bacterial infections. However, PGN fragments recently gained recognition as signalling molecules from the commensal gut microbiota in the healthy host. Here we focus on the minimal bioactive PGN motif muramyl dipeptide (MDP), found in both Gram-positive and Gram-negative commensal bacteria, which signals through the Nod2 receptor. MDP from the gut microbiota translocates to the brain and is associated with changes in neurodevelopment and behaviour, yet there is limited knowledge about the underlying mechanisms. In this study we demonstrate that physiologically relevant doses of MDP induce rapid changes in microglial gene expression and lead to cytokine and chemokine secretion. In immortalised microglial (IMG) cells, C-C Motif Chemokine Ligand 5 (CCL5/RANTES) expression is acutely sensitive to the lowest physiologically prevalent dose (0.1 µg/ml) of MDP. As CCL5 plays an important role in memory formation and synaptic plasticity, microglial CCL5 might be the missing link in elucidating MDP-induced alterations in synaptic gene expression. We observed that a higher physiological dose of MDP elevates the expression of cytokines TNF-α and IL-1ß, indicating a transition toward a pro-inflammatory phenotype in IMG cells, which was validated in primary microglial cultures. Furthermore, MDP induces the translocation of NF-κB subunit p65 into the nucleus, which is blocked by MAPK p38 inhibitor SB202190, suggesting that an interplay of both the NF-κB and MAPK pathways is responsible for the MDP-specific microglial phenotype. These findings underscore the significance of different MDP levels in shaping microglial function in the CNS and indicate MDP as a potential mediator for early inflammatory processes in the brain. It also positions microglia as an important target in the gut microbiota-brain-axis pathway through PGN signalling.

Toxicity Assessment of Environmental Liquid Crystal Monomers: A Bacteriological Investigation on Escherichia coli and Staphylococcus epidermidis.

The widespread existence of liquid crystal monomers (LCMs) in various environmental matrices has been demonstrated, yet studies on the toxicological effects of LCMs are considerably scarce and are urgently needed to be conducted to assess the adverse impacts on ecology and human health. Here, we conducted a bacteriological study on two representative human commensal bacteria, Escherichia coli (E. coli) and Staphylococcus epidermidis (S. epidermidis), to investigate the effect of LCMs at human-relevant dosage and maximum environmental concentration on growth, metabolome, enzymatic activity, and mRNA expression. Microbial growth results exhibited that the highest inhibition ratio of LCMs on S. epidermidis reached 33.6% in our set concentration range, while the corresponding data on E. coli was only 14.3%. Additionally, LCMs showed more dose-dependent toxicity to S. epidermidis rather than E. coli. A novel in vivo solid-phase microextraction (SPME) fiber was applied to capture the in vivo metabolites of microorganisms. In vivo metabolomic analyses revealed that dysregulated fatty acid metabolism-related products of both bacteria accounted for >50% of the total number of differential substances, and the results also showed the species-specific and concentration-dependent metabolic dysregulation in LCM-exposed bacteria. The determination of enzymatic activity and mRNA relative expression levels related to oxidative stress confirmed our speculation that the adverse effects were related to the oxidative metabolism of fatty acids. This study complements the gaps in toxicity data for LCMs against bacteria and provides a new and important insight regarding metabolic dysregulation induced by environmental LCMs in human commensal bacteria.

Research article antibody induction and immune response in nasal cavity by third dose of SARS-CoV-2 mRNA vaccination.

BACKGROUND: The mucosa serves as the first defence against pathogens and facilitates the surveillance and elimination of symbiotic bacteria by mucosal immunity. Recently, the mRNA vaccine against SARS-CoV-2 has been demonstrated to induce secretory antibodies in the oral and nasal cavities in addition to a systemic immune response. However, the mechanism of induced immune stimulation effect on mucosal immunity and commensal bacteria profile remains unclear. METHODS: Here, we longitudinally analysed the changing nasal microbiota and both systemic and nasal immune response upon SARS-CoV-2 mRNA vaccination, and evaluated how mRNA vaccination influenced nasal microbiota in 18 healthy participants who had received the third BNT162b. RESULTS: The nasal S-RBD IgG level correlated significantly with plasma IgG levels until 1 month and the levels were sustained for 3 months post-vaccination. In contrast, nasal S-RBD IgA induction peaked at 1 month, albeit slightly, and correlated only with plasma IgA, but the induction level decreased markedly at 3 months post-vaccination. 16 S rRNA sequencing of the nasal microbiota post-vaccination revealed not an overall change, but a decrease in certain opportunistic bacteria, mainly Fusobacterium. The decrease in these bacteria was more pronounced in those who exhibited nasal S-RBD IgA induction, and those with higher S-RBD IgA induction had lower relative amounts of potentially pathogenic bacteria such as Pseudomonas pre-vaccination. In addition, plasma and mucosal S-RBD IgG levels correlated with decreased commensal pathogens such as Finegoldia. CONCLUSIONS: These findings suggest that the third dose of SARS-CoV-2 mRNA vaccination induced S-RBD antibodies in the nasal mucosa and may have stimulated mucosal immunity against opportunistic bacterial pathogens. This effect, albeit probably secondary, may be considered one of the benefits of mRNA vaccination. Furthermore, our data suggest that a cooperative function of mucosal and systemic immunity in the reduction of bacteria and provides a better understanding of the symbiotic relationship between the host and bacteria in the nasal mucosa.

Fatal multiple organ dysfunction caused by commensal bacteria of urogenital tract infection in adult lung transplant recipients: two case reports.

BACKGROUND: Infection following lung transplantation has been the focus of clinical concerns. The colonization rate of commensal bacteria of the urogenital tract, including Mycoplasma hominis, Ureaplasma urealyticum (UU), and herpes simplex virus type-2 (HSV-2), is high, which may cause secondary infection after transplantation. CASE PRESENTATION: Twenty-three-year-old and 67-year-old women underwent lung transplantation for different causes. Shortly after the operation, they developed perineal skin ulcers, hypoxia, and intractable epilepsy. Subsequent computed tomography (CT) of the chest showed lung consolidation, and cranial CT showed shallowing sulci and gyri. UU and HSV-2 were detected in bronchoalveolar lavage fluid by next-generation sequencing, and HSV-2 was shown in the cerebrospinal fluid of both patients. Despite active treatment, both suffered irreversible brain function damage within 72 h of the seizure. CONCLUSIONS: Clinicians should know that commensal bacteria of urogenital tract infections can lead to fatal multiple organ dysfunction after lung transplantation.

Gut commensal bacteria exacerbate toxoplasmosis associated with TgSheepCHn5 (ToxoDB#2) and TgRedpandaCHn1 (ToxoDB#20) through Th1 immune response.

Oral infection of mice with several strains of Toxoplasma gondii results in intestinal pathological lesions, which contributes to the invasion of this parasite. However, the exact mechanism is unclear, and only a few strains have been explored. Here, T. gondii TgSheepCHn5 and TgRedpandaCHn1 strains from sheep and red panda were evaluated. The TgSheepCHn5 and TgRedpandaCHn1 strains induced intestinal lesions, loss of Paneth cells, and gut commensal bacteria dysbiosis in Swiss Webster mice. The lesions and loss of Paneth cells were dependent on IFN-γ and gut commensal bacteria during T. gondii infection. Deleting IFN-γ or gut commensal bacteria suppressed the Th1 immune response, alleviated the lesions and parasite loading, and upregulated the number of Paneth cells. Loss of IFN-γ production accelerated mice death, whereas the deletion of gut commensal bacteria enhanced the survival time of the host. The Th1 cell immune responses have positive and negative effects on toxoplasmosis, resistance to T. gondii infection, and acceleration intestine lesions. Adjustment of Th1 cell responses and gut commensal bacteria may be effective treatments for toxoplasmosis.

How Do Prebiotics Affect Human Intestinal Bacteria?-Assessment of Bacterial Growth with Inulin and XOS In Vitro.

Prebiotics are believed to exhibit high specificity in stimulating the growth or activity of a limited number of commensal microorganisms, thereby conferring health benefits to the host. However, the mechanism of action of prebiotics depends on multiple factors, including the composition of an individual's gut microbiota, and is therefore difficult to predict. It is known that different bacteria can utilize inulin and xylooligosaccharides (XOS), but an overview of which bacteria in the human gut may be affected is lacking. Detailed knowledge of how bacterial growth is affected by prebiotics is furthermore useful for the development of new synbiotics, which combine a living microorganism with a selective substrate to confer a health benefit to the host. Hence, we developed a statistical model to compare growth in vitro among typical human gut bacteria from different phylogenetic lineages. Based on continuous observation of the optical density (OD600), we compare maximal growth rates (rmax), maximal attained OD600 (ODmax), and area under the growth curve (AUC) of bacteria grown on inulin or XOS. The consideration of these three parameters suggests strain-specific preferences for inulin or XOS and reveals previously unknown preferences such as Streptococcus salivarius growth on XOS.

Predicting the pathogenicity of bacterial genomes using widely spread protein families.

BACKGROUND: The human body is inhabited by a diverse community of commensal non-pathogenic bacteria, many of which are essential for our health. By contrast, pathogenic bacteria have the ability to invade their hosts and cause a disease. Characterizing the differences between pathogenic and commensal non-pathogenic bacteria is important for the detection of emerging pathogens and for the development of new treatments. Previous methods for classification of bacteria as pathogenic or non-pathogenic used either raw genomic reads or protein families as features. Using protein families instead of reads provided a better interpretability of the resulting model. However, the accuracy of protein-families-based classifiers can still be improved. RESULTS: We developed a wide scope pathogenicity classifier (WSPC), a new protein-content-based machine-learning classification model. We trained WSPC on a newly curated dataset of 641 bacterial genomes, where each genome belongs to a different species. A comparative analysis we conducted shows that WSPC outperforms existing models on two benchmark test sets. We observed that the most discriminative protein-family features in WSPC are widely spread among bacterial species. These features correspond to proteins that are involved in the ability of bacteria to survive and replicate during an infection, rather than proteins that are directly involved in damaging or invading the host.

Streptococcus gordonii-Induced miRNAs Regulate CCL20 Responses in Human Oral Epithelial Cells.

The mechanisms through which oral commensal bacteria mitigates uncontrolled inflammatory responses of the oral mucosa remain unknown. Here, we show that representative oral bacterial species normally associated with oral health [S. gordonii (Sg), V. parvula (Vp), A. naeslundii (An), C. sputigena (Cs), and N. mucosa (Nm)] enhanced differential chemokine responses in oral epithelial cells (OECs), with some bacteria (An, Vp, and Nm) inducing higher chemokine levels (CXCL1, CXCL8) than others (Sg, Cs). Although all bacterial species (except Cs) increased CCL20 mRNA levels consistent with protein elevations in cell lysates, only An, Vp, and Nm induced higher CCL20 secretion, similar to the effect of the oral pathogen F. nucleatum (Fn). In contrast, most CCL20 remained associated with OECs exposed to Sg and negligible amounts released into the cell supernatants. Consistently, Sg attenuated An-induced CCL20. MiR-4516 and miR-663a were identified as Sg-specifically induced miRNAs modulating validated targets of chemokine-associated pathways. Cell transfection with miR-4516 and miR-663a decreased An- and Fn-induced CCL20. MiRNA upregulation and attenuation of An-induced CCL20 by Sg were reversed by catalase. Up-regulation of both miRNAs was specifically enhanced by oral streptococci H2O2-producers. These findings suggest that CCL20 levels produced by OECs in response to bacterial challenge are regulated by Sg-induced miR-4516 and miR-663a in a mechanism that involves hydrogen peroxide. This type of molecular mechanism could partly explain the central role of specific oral streptococcal species in balancing inflammatory and antimicrobial responses given the critical role of CCL20 in innate (antimicrobial) and adaptive immunity (modulates Th17 responses).

Litter Commensal Bacteria Can Limit the Horizontal Gene Transfer of Antimicrobial Resistance to Salmonella in Chickens.

Fostering a "balanced" gut microbiome through the administration of beneficial microbes that can competitively exclude pathogens has gained a lot of attention and use in human and animal medicine. However, little is known about how microbes affect the horizontal gene transfer of antimicrobial resistance (AMR). To shed more light on this question, we challenged neonatal broiler chicks raised on reused broiler chicken litter-a complex environment made up of decomposing pine shavings, feces, uric acid, feathers, and feed-with Salmonella enterica serovar Heidelberg (S. Heidelberg), a model pathogen. Neonatal chicks challenged with S. Heidelberg and raised on reused litter were more resistant to S. Heidelberg cecal colonization than chicks grown on fresh litter. Furthermore, chicks grown on reused litter were at a lower risk of colonization with S. Heidelberg strains that encoded AMR on IncI1 plasmids. We used 16S rRNA gene sequencing and shotgun metagenomics to show that the major difference between chicks grown on fresh litter and those grown on reused litter was the microbiome harbored in the litter and ceca. The microbiome of reused litter samples was more uniform and enriched in functional pathways related to the biosynthesis of organic and antimicrobial molecules than that in fresh litter samples. We found that Escherichia coli was the main reservoir of plasmids encoding AMR and that the IncI1 plasmid was maintained at a significantly lower copy per cell in reused litter compared to fresh litter. These findings support the notion that commensal bacteria play an integral role in the horizontal transfer of plasmids encoding AMR to pathogens like Salmonella. IMPORTANCE Antimicrobial resistance spread is a worldwide health challenge, stemming in large part from the ability of microorganisms to share their genetic material through horizontal gene transfer. To address this issue, many countries and international organizations have adopted a One Health approach to curtail the proliferation of antimicrobial-resistant bacteria. This includes the removal and reduction of antibiotics used in food animal production and the development of alternatives to antibiotics. However, there is still a significant knowledge gap in our understanding of how resistance spreads in the absence of antibiotic selection and the role commensal bacteria play in reducing antibiotic resistance transfer. In this study, we show that commensal bacteria play a key role in reducing the horizontal gene transfer of antibiotic resistance to Salmonella, provide the identity of the bacterial species that potentially perform this function in broiler chickens, and also postulate the mechanism involved.

Regulation of thermoregulatory behavior by commensal bacteria in Drosophila.

Commensal bacteria affect many aspects of host physiology. In this study, we focused on the role of commensal bacteria in the thermoregulatory behavior of Drosophila melanogaster. We demonstrated that the elimination of commensal bacteria caused an increase in the preferred temperature of Drosophila third-instar larvae without affecting the activity of transient receptor potential ankyrin 1 (TRPA1)-expressing thermosensitive neurons. We isolated eight bacterial strains from the gut and culture medium of conventionally reared larvae and found that the preferred temperature of the larvae was decreased by mono-association with Lactobacillus plantarum or Corynebacterium nuruki. Mono-association with these bacteria did not affect the indices of energy metabolism such as ATP and glucose levels of larvae, which are closely linked to thermoregulation in animals. Thus, we show a novel role for commensal bacteria in host thermoregulation and identify two bacterial species that affect thermoregulatory behavior in Drosophila.

Friend or Foe: Interbacterial Competition in the Nasal Cavity.

Like other microbes that live on or in the human body, the bacteria that inhabit the upper respiratory tract, in particular the nasal cavity, have evolved to survive in an environment that presents a number of physical and chemical challenges; these microbes are constantly bombarded with nutritional fluctuations, changes in humidity, the presence of inhaled particulate matter (odorants and allergens), and competition with other microbes. Indeed, only a specialized set of species is able to colonize this niche and successfully contend with the host's immune system and the constant threat from competitors. To this end, bacteria that live in the nasal cavity have evolved a variety of approaches to outcompete contenders for the limited nutrients and space; broadly speaking, these strategies may be considered a type of "bacterial warfare." A greater molecular understanding of bacterial warfare has the potential to reveal new approaches or molecules that can be developed as novel therapeutics. As such, there are many studies within the last decade that have sought to understand the complex polymicrobial interactions that occur in various environments. Here, we review what is currently known about the age-dependent structure and interbacterial relationships within the nasal microbiota and summarize the molecular mechanisms that are predicted to dictate bacterial warfare in this niche. Although the currently described interactions are complex, in reality, we have likely only scratched the surface in terms of a true understanding of the types of interbacterial competition and cooperation that are thought to take place in and on the human body.