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The gut microbiota produces high concentrations of antimicrobial short-chain fatty acids (SCFAs) that restrict the growth of invading microorganisms. The enteric pathogen Salmonella enterica serovar (S.) Typhimurium triggers inflammation in the large intestine to ultimately reduce microbiota density and bloom, but it is unclear how the pathogen gains a foothold in the homeostatic gut when SCFA-producing commensals are abundant. Here, we show that S. Typhimurium invasion of the ileal mucosa triggers malabsorption of dietary amino acids to produce downstream changes in nutrient availability in the large intestine. In gnotobiotic mice engrafted with a community of 17 human Clostridia isolates, S. Typhimurium virulence factors triggered marked changes in the cecal metabolome, including an elevated abundance of amino acids. In an ex vivo fecal culture model, we found that two of these amino acids, lysine and ornithine, countered SCFA-mediated growth inhibition by restoring S. Typhimurium pH homeostasis through the inducible amino acid decarboxylases CadA and SpeF, respectively. In a mouse model of gastrointestinal infection, S. Typhimurium CadA activity depleted dietary lysine to promote cecal ecosystem invasion in the presence of an intact microbiota. From these findings, we conclude that virulence factor-induced malabsorption of dietary amino acids in the small intestine changes the nutritional environment of the large intestine to provide S. Typhimurium with resources needed to counter growth inhibition by microbiota-derived SCFAs.

Changes in the composition of gut-associated microbial communities are associated with many human illnesses, but the factors driving dysbiosis remain incompletely understood. One factor governing the microbiota composition in the gut is bile. Bile acids shape the microbiota composition through their antimicrobial activity and by activating host signaling pathways that maintain gut homeostasis. Although bile acids are host-derived, their functions are integrally linked to bacterial metabolism, which shapes the composition of the intestinal bile acid pool. Conditions that change the size or composition of the bile acid pool can trigger alterations in the microbiota composition that exacerbate inflammation or favor infection with opportunistic pathogens. Therefore, manipulating the composition or size of the bile acid pool might be a promising strategy to remediate dysbiosis.

The gut microbiota prevents harmful microbes from entering the body, a function known as colonization resistance. The enteric pathogen Salmonella enterica serovar (S.) Typhimurium uses its virulence factors to break colonization resistance through unknown mechanisms. Using metabolite profiling and genetic analysis, we show that the initial rise in luminal pathogen abundance was powered by a combination of aerobic respiration and mixed acid fermentation of simple sugars, such as glucose, which resulted in their depletion from the metabolome. The initial rise in the abundance of the pathogen in the feces coincided with a reduction in the cecal concentrations of acetate and butyrate and an increase in epithelial oxygenation. Notably, these changes in the host environment preceded changes in the microbiota composition. We conclude that changes in the host environment can weaken colonization resistance even in the absence of overt compositional changes in the gut microbiota. [Display omitted] • Glucose fuels virulence factor-driven growth of Salmonella in the murine cecum • Colonization resistance becomes impaired when microbiota is compositionally intact • Colonization resistance is compromised when inflammation disrupts epithelial hypoxia • Aerobic respiration and fermentation of sugars support Salmonella outgrowth Rogers et al. show that Salmonella overcomes colonization resistance when the microbiota is compositionally intact by disrupting epithelial hypoxia. Pathogen outgrowth is fueled by catabolizing simple sugars, such as glucose, using a combination of aerobic respiration and mixed acid fermentation. [ABSTRACT FROM AUTHOR]

Little is known about the effect of gut microbial and extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) carriage, particularly in the general population. The aim of this study was to identify microbiota signatures uniquely correlated with ESBL-E carriage. We conducted a case–control study among individuals seeking care at the Sexual Health Clinic or Department of Infectious and Tropical Diseases, Saint-Antoine Hospital, Paris, France. Using coarsened exact matching, 176 participants with ESBL-carriage (i.e. cases) were matched 1:1 to those without ESBL-carriage (i.e. controls) based on sexual group, ESBL-E prevalence of countries travelled in <12 months, number of sexual partners in <6 months, geographic origin, and any antibiotic use in <6 months. 16S rRNA gene amplicon sequencing was used to generate differential abundances at the genus level and measures of α- and β-diversity. Participants were mostly men (83.2%, n = 293/352) and had a median age of 33 years (interquartile range: 27–44). Nine genera were found associated with ESBL-E carriage: Proteus (p < 0.0001), Carnobacterium (p < 0.0001), Enterorhabdus (p 0.0079), Catonella (p 0.017), Dermacoccus (p 0.017), Escherichia/Shigella (p 0.021), Kocuria (p 0.023), Bacillus (p 0.040), and Filifactor (p 0.043); however, differences were no longer significant after Benjamini–Hochberg correction (q > 0.05). There were no differences between those with versus without ESBL-E carriage in measures of α -diversity (Shannon Diversity Index, p 0.49; Simpson Diversity Index, p 0.54; and Chao1 Richness Estimator, p 0.16) or β -diversity (Bray–Curtis dissimilarity index, p 0.42). In this large carefully controlled study, there is lacking evidence that gut microbial composition and diversity is any different between individuals with and without ESBL-E carriage. [ABSTRACT FROM AUTHOR]

The gut microbiota is a complex and diverse community of microorganisms that colonizes the human gastrointestinal tract and influences various aspects of human health. These microbes are closely related to enteric infections. As a foreign entity for the host, commensal microbiota is restricted and regulated by the barrier and immune system in the gut and contributes to gut homeostasis. Commensals also effectively resist the colonization of pathogens and the overgrowth of indigenous pathobionts by utilizing a variety of mechanisms, while pathogens have developed strategies to subvert colonization resistance. Dysbiosis of the microbial community can lead to enteric infections. The microbiota acts as a pivotal mediator in establishing a harmonious mutualistic symbiosis with the host and shielding the host against pathogens. This review aims to provide a comprehensive overview of the mechanisms underlying hostmicrobiome and microbiome-pathogen interactions, highlighting the multifaceted roles of the gut microbiota in preventing enteric infections. We also discuss the applications of manipulating the microbiota to treat infectious diseases in the gut. [ABSTRACT FROM AUTHOR]

Bacterial extracellular vesicles (BEVs) are nano-sized lipid-shielded structures released by bacteria and that play an important role in intercellular communication. Their broad taxonomic origins and varying cargo compositions suggest their active participation in significant biological mechanisms. Specifically, they are involved in directly modulating microbial ecosystems, competing with other organisms, contributing to pathogenicity, and influencing the immunity of their hosts. This review examines the mechanisms that underlie the modulatory effects of BEVs on gut dynamics and immunity. Understanding how BEVs modulate microbiota composition and functional imbalances is crucial, as gut dysbiosis is implicated not only in the pathogenesis of various gastrointestinal, metabolic, and neurological diseases, but also in reducing resistance to colonization by enteric pathogens, which is particularly concerning given the current antimicrobial resistance crisis. This review summarizes recent advancements in the field of BEVs to encourage further research into these enigmatic entities. This will facilitate a better understanding of intra- and interkingdom communication phenomena and reveal promising therapeutic approaches.

The human gastrointestinal tract is colonized by a complex microbial ecosystem, the gut microbiota, which is pivotal in maintaining host health and mediating resistance to diseases. This review delineates colonization resistance (CR), a critical defensive mechanism employed by the gut microbiota to safeguard against pathogenic bacterial invasions, notably by Salmonella. We detail the mechanisms through which the gut microbiota impedes Salmonella colonization, including nutrient competition, production of antimicrobial peptides, synthesis of microbial-derived metabolites, and modulation of the host immune response. Additionally, we examine how dietary interventions can influence these mechanisms, thereby augmenting the protective role of the gut microbiota. The review also discusses the sophisticated strategies utilized by Salmonella to overcome these microbial defenses. A thorough understanding of these complex interactions between microbial symbionts and pathogens is crucial for the development of innovative therapeutic strategies that enhance CR, aiming to prevent or treat microbial infections effectively.

ABSTRACT Diverse gut microorganisms present in humans and mice are essential for the prevention of microbial pathogen colonization. However, antibiotic-induced dysbiosis of the gut microbiome reduces microbial diversity and allows Clostridioides difficile (C. difficile) to colonize the intestine. The Oligo-Mouse-Microbiota 19.1 (OMM19.1) is a synthetic community that consists of bacteria that are taxonomically and functionally designed to mimic the specific pathogen-free mouse gut microbiota. Here, we examined the susceptibility of OMM19.1 colonized mice to C. difficile infection (CDI) at a range of infectious doses (103, 105, and 107 spores) without prior antibiotic treatment. We found that mice colonized with OMM19.1 were susceptible to CDI regardless of the dose. The clinical scores increased with increasing C. difficile dosage. Infection with C. difficile was correlated with a significant increase in Ligilactobacillus murinus and Escherichia coli, while the relative abundance of Bacteroides caecimuris, Akkermansia muciniphila, Extibacter muris, and Turicimonas muris was significantly decreased following CDI. Our results demonstrate that the OMM19.1 community requires additional bacteria to enable C. difficile colonization resistance.IMPORTANCEThe human gut microbiota consists of a wide range of microorganisms whose composition and function vary according to their location and have a significant impact on health and disease. The ability to generate and test the defined microbiota within gnotobiotic animal models is essential for determining the mechanisms responsible for colonization resistance. The exact mechanism(s) by which healthy microbiota prevents Clostridioides difficile infection is unknown, although competition for nutrients, active antagonism, production of inhibitory metabolites (such as secondary bile acids), and microbial manipulation of the immune system are all thought to play a role. Here, we colonized germ-free C57BL/6 mice with a synthetic bacterial community (OMM19.1) that mimics the specific pathogen-free mouse microbiota. Following breeding, to enable immune system development, F1 mice were infected with three different doses of C. difficile. Our research suggests that there are additional essential microbial functions that are absent from the current OMM19.1 model.

Abstract Probiotics offer a promising prophylactic approach against various pathogens and represent an alternative strategy to combat biofilm-related infections. In this study, we isolated vaginal commensal microbiota from 54 healthy Indian women to investigate their probiotic traits. We primarily explored the ability of cell-free supernatant (CFS) from Lactobacilli to prevent Uropathogenic Escherichia coli (UPEC) colonization and biofilm formation. Our findings revealed that CFS effectively reduced UPEC’s swimming and swarming motility, decreased cell surface hydrophobicity, and hindered matrix production by downregulating specific genes (fimA, fimH, papG, and csgA). Subsequent GC–MS analysis identified Tryptamine, a monoamine compound, as the potent bioactive substance from Lactobacilli CFS, inhibiting UPEC biofilms with an MBIC of 4 µg/ml and an MBEC of 8 µg/ml. Tryptamine induced significant changes in E. coli colony biofilm morphology, transitioning from the Red, Dry, and Rough (RDAR) to the Smooth and White phenotype, indicating reduced extracellular matrix production. Biofilm time-kill assays demonstrated a four-log reduction in UPEC viability when treated with Tryptamine, highlighting its potent antibacterial properties, comparable to CFS treatment. Biofilm ROS assays indicated a significant elevation in ROS generation within UPEC biofilms, suggesting a potential antibacterial mechanism. Gene expression studies with Tryptamine-treated samples showed a reduction in expression of curli gene (csgA), consistent with CFS treatment. This study underscores the potential of Tryptamine from probiotic Lactobacilli CFS as a promising antibiofilm agent against UPEC biofilms.

Introduction: The microbiome is known to have a substantial impact on human health and disease. However, the impacts of the microbiome on immune system development, susceptibility to infectious diseases, and vaccine-elicited immune responses are emerging areas of interest. Areas covered: In this review, we provide an overview of development of the microbiome during childhood. We highlight available data suggesting that the microbiome is critical to maturation of the immune system and modifies susceptibility to a variety of infections during childhood and adolescence, including respiratory tract infections, Clostridioides difficile infection, and sexually transmitted infections. We discuss currently available and investigational therapeutics that have the potential to modify the microbiome to prevent or treat infections among children. Finally, we review the accumulating evidence that the gut microbiome influences vaccine-elicited immune responses among children. Expert opinion: Recent advances in sequencing technologies have led to an explosion of studies associating the human microbiome with the risk and severity of infectious diseases. As our knowledge of the extent to which the microbiome influences childhood infections continues to grow, microbiome-based diagnostics and therapeutics will increasingly be incorporated into clinical practice to improve the prevention, diagnosis, and treatment of infectious diseases among children. [ABSTRACT FROM AUTHOR]

Colonization resistance, conferred by the host's microbiota through both direct and indirect protective actions, serves to protect the host from enteric infections. Here, we identified the specific members of the gut microbiota that impact gastrointestinal colonization by Citrobacter rodentium, a murine pathogen causing colonic crypt hyperplasia. The gut colonization levels of C. rodentium in C57BL/6 mice varied among breeding facilities, probably due to differences in microbiota composition. A comprehensive analysis of the microbiota revealed that specific members of the microbiota may influence gut colonization by C. rodentium, thus providing a potential link between the two. [ABSTRACT FROM AUTHOR]

A healthy animal intestine hosts a diverse population of bacteria in a symbiotic relationship. These bacteria utilize nutrients in the host's intestinal environment for growth and reproduction. In return, they assist the host in digesting and metabolizing nutrients, fortifying the intestinal barrier, defending against potential pathogens, and maintaining gut health. Bacterial colonization is a crucial aspect of this interaction between bacteria and the intestine and involves the attachment of bacteria to intestinal mucus or epithelial cells through nonspecific or specific interactions. This process primarily relies on adhesins. The binding of bacterial adhesins to host receptors is a prerequisite for the long-term colonization of bacteria and serves as the foundation for the pathogenicity of pathogenic bacteria. Intervening in the adhesion and colonization of bacteria in animal intestines may offer an effective approach to treating gastrointestinal diseases and preventing pathogenic infections. Therefore, this paper reviews the situation and mechanisms of bacterial colonization, the colonization characteristics of various bacteria, and the factors influencing bacterial colonization. The aim of this study was to serve as a reference for further research on bacteria–gut interactions and improving animal gut health. [ABSTRACT FROM AUTHOR]

Background: The potential for promotion of intestinal colonization with healthcare-associated pathogens by new antibiotics used to treat infections due to multidrug-resistant Gram-negative bacilli is unclear. Methods: Mice treated for 3 days with daily subcutaneous phosphate-buffered saline (control), ceftazidime/avibactam, ceftolozane/tazobactam, ceftaroline, and meropenem/vaborbactam were challenged with 10,000 colony-forming units (CFU) of vancomycin-resistant Enterococcus (VRE) resistant to each of the antibioics or carbapenemase-producing Klebsiella pneumoniae 1 day after the final treatment dose. The concentrations of VRE or K. pneumoniae in stool were measured on days 1, 3, 6, and 15 after challenge. Results: Control mice had transient low levels of VRE or K. pneumoniae (8 log10 CFU/g of stool on day 1 after challenge) that persisted at >4 log10 CFU/g of stool through day 15 (P8 log10 CFU/g of stool) (P5 log10 CFU/g of stool), and ceftazidime/avibactam did not promote colonization (P>0.05). Conclusions: Our results suggest that several beta-lactam antibiotics recently developed for treatment of infections with resistant Gram-negative bacilli have the potential to promote colonization by healthcare-associated pathogens. Additional studies are needed to examine the impact of these agents in patients.

Entomopathogenic fungi (EPF), which have convergently evolved from different fungal phyla, play a pivotal role in regulating insect populations by infecting hosts via cuticle penetration instead of per os ingestion. Ascomycete EPF are evolutionarily closer to plant pathogenic fungi rather than mammalian pathogens, and the representative species have been developed and used in agriculture as ecofriendly mycoinsecticides. The stepwise infection of EPF can be divided into two essential processes: cuticle penetration and hemocoel colonization. Diverse genes, pathways, and small molecules have been characterized with specific contributions to fungal infection steps. EPF also have to outcompete insect cuticular microbiotas before they can breach insect cuticles, which expands the bilateral fungus–insect interactions to a multipartite level. Further investigations of EPF virulence effectors, chemical biology, and epigenetic controls will deepen our understanding of EPF pathobiology and pathoecology. Entomopathogenic fungi (EPF) distribute in different fungal phyla with variable host ranges and play essential role in regulating insect populations by infecting hosts via cuticle penetration. The representative ascomycete EPF of Metarhizium and Beauveria species have been widely used in mechanistic investigations of fungus–insect interactions and as ecofriendly mycoinsecticides. Here, we review the function of diverse genes, pathways, and secondary metabolites associated with EPF stepwise infections. In particular, emerging evidence has shown that EPF have to outcompete insect ectomicrobiotas prior to penetrating cuticles, and subvert or evade host antifungal immunity by using effector-like proteins and chemicals like plant pathogens. Future prospects are discussed for a better understanding of fungal pathobiology, which will provide novel insights into microbe–animal interactions. [ABSTRACT FROM AUTHOR]

Among the most frequently reported diseases of rabbits, the main place is occupied by diseases of bacterial etiology, the pathogens of which are characterized by multidrug resistance. The aim of the study was to analyze the dynamics of morphometric indicators during experimental infection of rabbits with Pseudomonas aeruginosa bacteria. When assessing colonization resistance of organs, the following indicators were taken into account: colonization index, ratio of the number of microorganisms isolated from nasal cavity washes, contents of cecum of clinically healthy and sick animals. Significant changes in morphological parameters (p 0.05) were revealed during the isolation of P. aeruginosa from blood, lymph nodes, spleen, liver, and kidneys of sick rabbits. Overgrowth of isolates producing adhesive antigens, hemolysins, bacteriocins should be considered as prognostic markers of connective tissue dysplasia. The initiation, development, and outcome of microbial overgrowth syndrome are mediated by morphofunctional changes in compensatory mechanisms of mucociliary clearance system and colonization resistance.

Abstract Background The establishment of a robust gut microbiota in piglets during their early developmental stage holds the potential for long-term advantageous effects. However, the optimal timeframe for introducing probiotics to achieve this outcome remains uncertain. Results In the context of this investigation, we conducted a longitudinal assessment of the fecal microbiota of 63 piglets at three distinct pre-weaning time points. Simultaneously, we gathered vaginal and fecal samples from 23 sows. Employing 16S rRNA gene and metagenomic sequencing methodologies, we conducted a comprehensive analysis of the fluctuation patterns in microbial composition, functional capacity, interaction networks, and colonization resistance within the gut microbiota of piglets. As the piglets progressed in age, discernible modifications in intestinal microbial diversity, composition, and function were observed. A source-tracking analysis unveiled the pivotal role of fecal and vaginal microbiota derived from sows in populating the gut microbiota of neonatal piglets. By D21, the microbial interaction network displayed a more concise and efficient configuration, accompanied by enhanced colonization resistance relative to the other two time points. Moreover, we identified three strains of Ruminococcus sp. at D10 as potential candidates for improving piglets' weight gain during the weaning phase. Conclusions The findings of this study propose that D10 represents the most opportune juncture for the introduction of external probiotic interventions during the early stages of piglet development. This investigation augments our comprehension of the microbiota dynamics in early-life of piglets and offers valuable insights for guiding forthcoming probiotic interventions.

An intact gut microbiota confers colonization resistance against Clostridioides difficile through a variety of mechanisms, likely including competition for nutrients. Recently, proline was identified as an important environmental amino acid that C. difficile uses to support growth and cause significant disease. A posttranslationally modified form, trans-4-hydroxyproline, is highly abundant in collagen, which is degraded by host proteases in response to C. difficile toxin activity. The ability to dehydrate trans-4-hydroxyproline via the HypD glycyl radical enzyme is widespread among gut microbiota, including C. difficile and members of the commensal Clostridia, suggesting that this amino acid is an important nutrient in the host environment. Therefore, we constructed a C. difficile ΔhypD mutant and found that it was modestly impaired in fitness in a mouse model of infection, and was associated with an altered microbiota when compared to mice challenged with the wild-type strain. Changes in the microbiota between the two groups were largely driven by members of the Lachnospiraceae family and the Clostridium genus. We found that C. difficile and type strains of three commensal Clostridia had significant alterations to their metabolic gene expression in the presence of trans-4-hydroxyproline in vitro. The proline reductase (prd) genes were elevated in C. difficile, consistent with the hypothesis that trans-4-hydroxyproline is used by C. difficile to supply proline for energy metabolism. Similar transcripts were also elevated in some commensal Clostridia tested, although each strain responded differently. This suggests that the uptake and utilization of other nutrients by the commensal Clostridia may be affected by trans-4-hydroxyproline metabolism, highlighting how a common nutrient may be a signal to each organism to adapt to a unique niche. Further elucidation of the differences between them in the presence of hydroxyproline and other key nutrients will be important in determining their role in nutrient competition against C. difficile. IMPORTANCE Proline is an essential environmental amino acid that C. difficile uses to support growth and cause significant disease. A posttranslationally modified form, hydroxyproline, is highly abundant in collagen, which is degraded by host proteases in response to C. difficile toxin activity. The ability to dehydrate hydroxyproline via the HypD glycyl radical enzyme is widespread among gut microbiota, including C. difficile and members of the commensal Clostridia, suggesting that this amino acid is an important nutrient in the host environment. We found that C. difficile and three commensal Clostridia strains had significant, but different, alterations to their metabolic gene expression in the presence of hydroxyproline in vitro. This suggests that the uptake and utilization of other nutrients by the commensal Clostridia may be affected by hydroxyproline metabolism, highlighting how a common nutrient may be a signal to each organism to adapt to a unique niche. Further elucidation of the differences between them in the presence of hydroxyproline and other key nutrients will be important to determining their role in nutrient competition against C. difficile.

Bacteria are efficient colonizers of a wide range of secluded microhabitats, such as soil pores, skin follicles, or intestinal crypts. How the structural diversity of these habitats modulates microbial self-organization remains poorly understood, in part because of the difficulty to precisely manipulate the physical structure of microbial environments. Using a microfluidic device to grow bacteria in crypt-like incubation chambers of systematically varied lengths, we show that small variations in the physical structure of the microhabitat can drastically alter bacterial colonization success and resistance against invaders. Small crypts are uncolonizable; intermediately sized crypts can stably support dilute populations, while beyond a second critical length scale, populations phase separate into a dilute region and a jammed region. The jammed state is characterized by extreme colonization resistance, even if the resident strain is suppressed by an antibiotic. Combined with a flexible biophysical model, we demonstrate that colonization resistance and associated priority effects can be explained by a crowding-induced phase transition, which results from a competition between proliferation and density-dependent cell leakage. The emerging sensitivity to scale underscores the need to control for scale in microbial ecology experiments. Systematic flow-adjustable length-scale variations may serve as a promising strategy to elucidate further scale-sensitive tipping points and to rationally modulate the stability and resilience of microbial colonizers.

ABSTRACTA complex microbial community in the gut may prevent the colonization of enteric pathogens such as Salmonella. Some individual or a combination of species in the gut may confer colonization resistance against Salmonella. To gain a better understanding of the colonization resistance against Salmonella enterica, we isolated a library of 1,300 bacterial strains from feral chicken gut microbiota which represented a total of 51 species. Using a co-culture assay, we screened the representative species from this library and identified 30 species that inhibited Salmonella enterica subspecies enterica serovar Typhimurium in vitro. To improve the Salmonella inhibition capacity, from a pool of fast-growing species, we formulated 66 bacterial blends, each of which composed of 10 species. Bacterial blends were more efficient in inhibiting Salmonella as compared to individual species. The blend that showed maximum inhibition (Mix10) also inhibited other serotypes of Salmonella frequently found in poultry. The in vivo effect of Mix10 was examined in a gnotobiotic and conventional chicken model. The Mix10 consortium significantly reduced Salmonella load at day 2 post-infection in gnotobiotic chicken model and decreased intestinal tissue damage and inflammation in both models. Cell-free supernatant of Mix10 did not show Salmonella inhibition, indicating that Mix10 inhibits Salmonella through either nutritional competition, competitive exclusion, or through reinforcement of host immunity. Out of 10 species, 3 species in Mix10 did not colonize, while 3 species constituted more than 70% of the community. Two of these species were previously uncultured bacteria. Our approach could be used as a high-throughput screening system to identify additional bacterial sub-communities that confer colonization resistance against enteric pathogens and its effect on the host.IMPORTANCESalmonella colonization in chicken and human infections originating from Salmonella-contaminated poultry is a significant problem. Poultry has been identified as the most common food linked to enteric pathogen outbreaks in the United States. Since multi-drug-resistant Salmonella often colonize chicken and cause human infections, methods to control Salmonella colonization in poultry are needed. The method we describe here could form the basis of developing gut microbiota-derived bacterial blends as a microbial ecosystem therapeutic against Salmonella.

ABSTRACTColonization of human skin and nares by methicillin-resistant Staphylococcus aureus (MRSA) leads to the community spread of MRSA. This spread is exacerbated by the transfer of MRSA between humans and livestock, particularly swine. Here, we capitalized on the shared features between human and porcine skin, including shared MRSA colonization, to study novel bacterial mediators of MRSA colonization resistance. We focused on the poorly studied bacterial species Desemzia incerta, which we found to exert antimicrobial activity through a secreted product and exhibited colonization resistance against MRSA in an in vivo murine skin model. Using parallel genomic and biochemical investigation, we discovered that D. incerta secretes an antimicrobial protein. Sequential protein purification and proteomics analysis identified 24 candidate inhibitory proteins, including a promising peptidoglycan hydrolase candidate. Aided by transcriptional analysis of D. incerta and MRSA cocultures, we found that exposure to D. incerta leads to decreased MRSA biofilm production. These results emphasize the value of exploring microbial communities across a spectrum of hosts, which can lead to novel therapeutic agents as well as an increased understanding of microbial competition.IMPORTANCEMethicillin-resistant Staphylococcus aureus (MRSA) causes a significant healthcare burden and can be spread to the human population via livestock transmission. Members of the skin microbiome can prevent MRSA colonization via a poorly understood phenomenon known as colonization resistance. Here, we studied the colonization resistance of S. aureus by bacterial inhibitors previously identified from a porcine skin model. We identify a pig skin commensal, Desemzia incerta, that reduced MRSA colonization in a murine model. We employ a combination of genomic, proteomic, and transcriptomic analyses to explore the mechanisms of inhibition between D. incerta and S. aureus. We identify 24 candidate antimicrobial proteins secreted by D. incerta that could be responsible for its antimicrobial activity. We also find that exposure to D. incerta leads to decreased S. aureus biofilm formation. These findings show that the livestock transmission of MRSA can be exploited to uncover novel mechanisms of MRSA colonization resistance.

Avian malaria infection has been known to affect host microbiota, but the impact of Plasmodium infection on the colonization resistance in bird gut microbiota remains unexplored. This study investigated the dynamics of Plasmodium relictum infection in canaries, aiming to explore the hypothesis that microbiota modulation by P. relictum would reduce colonization resistance. Canaries were infected with P. relictum, while a control group was maintained. The results revealed the presence of P. relictum in the blood of all infected canaries. Analysis of the host microbiota showed no significant differences in alpha diversity metrics between infected and control groups. However, significant differences in beta diversity indicated alterations in the microbial taxa composition of infected birds. Differential abundance analysis identified specific taxa with varying prevalence between infected and control groups at different time points. Network analysis demonstrated a decrease in correlations and revealed that P. relictum infection compromised the bird microbiota's ability to resist the removal of taxa but did not affect network robustness with the addition of new nodes. These findings suggest that P. relictum infection reduces gut microbiota stability and has an impact on colonization resistance. Understanding these interactions is crucial for developing strategies to enhance colonization resistance and maintain host health in the face of parasitic infections. [ABSTRACT FROM AUTHOR]

Introduction: Campylobacter jejuni stands out as one of the leading causes of bacterial enteritis. In contrast to humans, specific pathogen-free (SPF) laboratory mice display strict intestinal colonization resistance (CR) against C. jejuni, orchestrated by the specific murine intestinal microbiota, as shown by fecal microbiota transplantation (FMT) earlier. Methods: Murine infection models, comprising SPF, SAB, hma, and mma mice were employed. FMT and microbiota depletion were confirmed by culture and culture-independent analyses. Targeted metabolome analyses of fecal samples provided insights into the associated metabolomic signatures. Results: In comparison to hma mice, the murine intestinal microbiota of mma and SPF mice (with CR against C. jejuni) contained significantly elevated numbers of lactobacilli, and Mouse Intestinal Bacteroides, whereas numbers of enterobacteria, enterococci, and Clostridium coccoides group were reduced. Targeted metabolome analysis revealed that fecal samples from mice with CR contained increased levels of secondary bile acids and fatty acids with known antimicrobial activities, but reduced concentrations of amino acids essential for C. jejuni growth as compared to control animals without CR. Discussion: The findings highlight the role of microbiota-mediated nutrient competition and antibacterial activities of intestinal metabolites in driving murine CR against C. jejuni. The study underscores the complex dynamics of hostmicrobiota-pathogen interactions and sets the stage for further investigations into the mechanisms driving CR against enteric infections. [ABSTRACT FROM AUTHOR]

Background: The establishment of a robust gut microbiota in piglets during their early developmental stage holds the potential for long-term advantageous effects. However, the optimal timeframe for introducing probiotics to achieve this outcome remains uncertain. Results: In the context of this investigation, we conducted a longitudinal assessment of the fecal microbiota of 63 piglets at three distinct pre-weaning time points. Simultaneously, we gathered vaginal and fecal samples from 23 sows. Employing 16S rRNA gene and metagenomic sequencing methodologies, we conducted a comprehensive analysis of the fluctuation patterns in microbial composition, functional capacity, interaction networks, and colonization resistance within the gut microbiota of piglets. As the piglets progressed in age, discernible modifications in intestinal microbial diversity, composition, and function were observed. A source-tracking analysis unveiled the pivotal role of fecal and vaginal microbiota derived from sows in populating the gut microbiota of neonatal piglets. By D21, the microbial interaction network displayed a more concise and efficient configuration, accompanied by enhanced colonization resistance relative to the other two time points. Moreover, we identified three strains of Ruminococcus sp. at D10 as potential candidates for improving piglets' weight gain during the weaning phase. Conclusions: The findings of this study propose that D10 represents the most opportune juncture for the introduction of external probiotic interventions during the early stages of piglet development. This investigation augments our comprehension of the microbiota dynamics in early-life of piglets and offers valuable insights for guiding forthcoming probiotic interventions. [ABSTRACT FROM AUTHOR]

The gut microbiome is intimately intertwined with the host immune system, having effects on the systemic immune system. Dysbiosis of the gut microbiome has been linked not only to gastrointestinal disorders but also conditions of the skin, lungs, and brain. Commensal bacteria can affect the immune status of the host through a stimulation of the innate immune system, training of the adaptive immune system, and competitive exclusion of pathogens. Commensal bacteria improve immune response through the production of immunomodulating compounds such as microbe-associated molecular patterns (MAMPs), short-chain fatty acids (SCFAs), and secondary bile acids. The microbiome, especially when in dysbiosis, is plastic and can be manipulated through the introduction of beneficial bacteria or the adjustment of nutrients to stimulate the expansion of beneficial taxa. The complex nature of the gastrointestinal tract (GIT) ecosystem complicates the use of these methods, as similar treatments have various results in individuals with different residential microbiomes and differential health statuses. A more complete understanding of the interaction between commensal species, host genetics, and the host immune system is needed for effective microbiome interventions to be developed and implemented in a clinical setting. [ABSTRACT FROM AUTHOR]

A balanced gut microbiota contributes to health, but the mechanisms maintaining homeostasis remain elusive. Microbiota assembly during infancy is governed by competition between species and by environmental factors, termed habitat filters, that determine the range of successful traits within the microbial community. These habitat filters include the diet, host-derived resources, and microbiota-derived metabolites, such as short-chain fatty acids. Once the microbiota has matured, competition and habitat filtering prevent engraftment of new microbes, thereby providing protection against opportunistic infections. Competition with endogenous Enterobacterales, habitat filtering by short-chain fatty acids, and a host-derived habitat filter, epithelial hypoxia, also contribute to colonization resistance against Salmonella serovars. However, at a high challenge dose, these frank pathogens can overcome colonization resistance by using their virulence factors to trigger intestinal inflammation. In turn, inflammation increases the luminal availability of host-derived resources, such as oxygen, nitrate, tetrathionate, and lactate, thereby creating a state of abnormal habitat filtering that enables the pathogen to overcome growth inhibition by short-chain fatty acids. Thus, studying the process of ecosystem invasion by Salmonella serovars clarifies that colonization resistance can become weakened by disrupting host-mediated habitat filtering. This insight is relevant for understanding how inflammation triggers dysbiosis linked to noncommunicable diseases, conditions in which endogenous Enterobacterales expand in the fecal microbiota using some of the same growth-limiting resources required by Salmonella serovars for ecosystem invasion. In essence, ecosystem invasion by Salmonella serovars suggests that homeostasis and dysbiosis simply represent states where competition and habitat filtering are normal or abnormal, respectively.

Upon ingestion from an infected host, tick-borne pathogens (TBPs) have to overcome colonization resistance, a defense mechanism by which tick microbiota prevent microbial invasions. Previous studies have shown that the pathogen Anaplasma phagocytophilum alters the microbiota composition of the nymphs of Ixodes scapularis, but its impact on tick colonization resistance remains unclear. We analyzed tick microbiome genetic data using published Illumina 16S rRNA sequences, assessing microbial diversity within ticks (alpha diversity) through species richness, evenness, and phylogenetic diversity. We compared microbial communities in ticks with and without infection with A. phagocytophilum (beta diversity) using the Bray-Curtis index. We also built co-occurrence networks and used node manipulation to study the impact of A. phagocytophilum on microbial assembly and network robustness, crucial for colonization resistance. We examined network robustness by altering its connectivity, observing changes in the largest connected component (LCC) and the average path length (APL). Our findings revealed that infection with A. phagocytophilum does not significantly alter the overall microbial diversity in ticks. Despite a decrease in the number of nodes and connections within the microbial networks of infected ticks, certain core microbes remained consistently interconnected, suggesting a functional role. The network of infected ticks showed a heightened vulnerability to node removal, with smaller LCC and longer APL, indicating reduced resilience compared to the network of uninfected ticks. Interestingly, adding nodes to the network of infected ticks led to an increase in LCC and a decrease in APL, suggesting a recovery in network robustness, a trend not observed in networks of uninfected ticks. This improvement in network robustness upon node addition hints that infection with A. phagocytophilum might lower ticksʼ resistance to colonization, potentially facilitating further microbial invasions. We conclude that the compromised colonization resistance observed in tick microbiota following infection with A. phagocytophilum may facilitate co-infection in natural tick populations.

IntroductionCampylobacter jejuni stands out as one of the leading causes of bacterial enteritis. In contrast to humans, specific pathogen-free (SPF) laboratory mice display strict intestinal colonization resistance (CR) against C. jejuni, orchestrated by the specific murine intestinal microbiota, as shown by fecal microbiota transplantation (FMT) earlier.MethodsMurine infection models, comprising SPF, SAB, hma, and mma mice were employed. FMT and microbiota depletion were confirmed by culture and culture-independent analyses. Targeted metabolome analyses of fecal samples provided insights into the associated metabolomic signatures.ResultsIn comparison to hma mice, the murine intestinal microbiota of mma and SPF mice (with CR against C. jejuni) contained significantly elevated numbers of lactobacilli, and Mouse Intestinal Bacteroides, whereas numbers of enterobacteria, enterococci, and Clostridium coccoides group were reduced. Targeted metabolome analysis revealed that fecal samples from mice with CR contained increased levels of secondary bile acids and fatty acids with known antimicrobial activities, but reduced concentrations of amino acids essential for C. jejuni growth as compared to control animals without CR.DiscussionThe findings highlight the role of microbiota-mediated nutrient competition and antibacterial activities of intestinal metabolites in driving murine CR against C. jejuni. The study underscores the complex dynamics of host-microbiota-pathogen interactions and sets the stage for further investigations into the mechanisms driving CR against enteric infections.

ABSTRACTGut microbiota plays a crucial role in providing colonization resistance against multi-drug resistant organisms including carbapenem-resistant Klebsiella pneumoniae (CRKP). However, the impact of different carbapenems on intestinal colonization resistance against CRKP remains poorly understood. In this study, we aimed to investigate the effects of three commonly used carbapenems (meropenem, imipenem, and ertapenem) administered at single-day doses, which are typically employed in emergency departments for managing infected patients, on CRKP gut colonization. We conducted experiments in mice by intravenously administering each carbapenem using human-simulated one-day regimens. The composition of the gut microbiota was analyzed using 16S rRNA amplicon sequencing before and after carbapenem administration. Our results revealed that all three carbapenems, when administered at a single-day dose significantly altered the abundance and diversity of the gut microbiota, leading to compromised colonization resistance against CRKP. Notably, the ertapenem and imipenem groups showed an increase in Allobaculum, Bifidobacterium, Enterobacteriaceae, while the meropenem and imipenem groups exhibited a decrease in Ruminococcaceae, S24-7, and Akkermania. Additionally, the Shannon index exhibited a negative correlation with both the number of days of CRKP colonization CFUs and the duration of bacteria shedding. Furthermore, the count of CRKP in mice after ertapenem administration on the first day and the duration of CRKP shedding were significantly lower compared to meropenem and imipenem. Predictive metabolic pathway analysis demonstrated that the three carbapenems similarly affected a range of metabolic pathways of gut microflora, including carbohydrate metabolism and vitamin B. Our findings emphasize that ertapenem, with its relatively narrow spectrum, minimizes perturbations of the gut microbiota and has a relatively less impact on gut colonization resistance against CRKP.IMPORTANCEThe intestinal colonization of carbapenem-resistant Klebsiella pneumoniae (CRKP) is an important source of clinical infection. Our research showed that even single-day dose use of carbapenems caused CRKP colonization and continuous bacterial shedding, which reminds clinical doctors to prescribe carbapenems cautiously. Whenever possible, ertapenem should be the preferred choice over other carbapenems especially when the identified or highly suspected pathogens can be effectively targeted by ertapenem.

ABSTRACTChanges in the composition of gut-associated microbial communities are associated with many human illnesses, but the factors driving dysbiosis remain incompletely understood. One factor governing the microbiota composition in the gut is bile. Bile acids shape the microbiota composition through their antimicrobial activity and by activating host signaling pathways that maintain gut homeostasis. Although bile acids are host-derived, their functions are integrally linked to bacterial metabolism, which shapes the composition of the intestinal bile acid pool. Conditions that change the size or composition of the bile acid pool can trigger alterations in the microbiota composition that exacerbate inflammation or favor infection with opportunistic pathogens. Therefore, manipulating the composition or size of the bile acid pool might be a promising strategy to remediate dysbiosis.

ABSTRACTL-arginine (L-arg) is a versatile amino acid and a central intestinal metabolite in mammalian and microbial organisms. Thus, L-arg participates as precursor of multiple metabolic pathways in the regulation of cell division and growth. It also serves as a source of carbon, nitrogen, and energy or as a substrate for protein synthesis. Consequently, L-arg can simultaneously modify mammalian immune functions, intraluminal metabolism, intestinal microbiota, and microbial pathogenesis. While dietary intake, protein turnover or de novo synthesis usually supply L-arg in sufficient amounts, the expression of several key enzymes of L-arg metabolism can change rapidly and dramatically following inflammation, sepsis, or injury. Consequently, the availability of L-arg can be restricted due to increased catabolism, transforming L-arg into an essential amino acid. Here, we review the enzymatic pathways of L-arg metabolism in microbial and mammalian cells and their role in immune function, intraluminal metabolism, colonization resistance, and microbial pathogenesis in the gut.

ABSTRACTCandida albicans is a commensal yeast present in the gut of most healthy individuals but with highly variable concentrations. However, little is known about the host factors that influence colonization densities. We investigated how microbiota, host lifestyle factors, and genetics could shape C. albicans intestinal carriage in 695 healthy individuals from the Milieu Intérieur cohort. C. albicans intestinal carriage was detected in 82.9% of the subjects using quantitative PCR. Using linear mixed models and multiway-ANOVA, we explored C. albicans intestinal levels with regard to gut microbiota composition and lifestyle factors including diet. By analyzing shotgun metagenomics data and C. albicans qPCR data, we showed that Intestinimonas butyriciproducens was the only gut microbiota species whose relative abundance was negatively correlated with C. albicans concentration. Diet is also linked to C. albicans growth, with eating between meals and a low-sodium diet being associated with higher C. albicans levels. Furthermore, by Genome-Wide Association Study, we identified 26 single nucleotide polymorphisms suggestively associated with C. albicans colonization. In addition, we found that the intestinal levels of C. albicans might influence the host immune response, specifically in response to fungal challenge. We analyzed the transcriptional levels of 546 immune genes and the concentration of 13 cytokines after whole blood stimulation with C. albicans cells and showed positive associations between the extent of C. albicans intestinal levels and NLRP3 expression, as well as secreted IL-2 and CXCL5 concentrations. Taken together, these findings open the way for potential new interventional strategies to curb C. albicans intestinal overgrowth.

Multispecies community composition and dynamics are key to health and disease across biological systems, a prominent example being microbial ecosystems. Explaining the forces that govern diversity and resilience in the microbial consortia making up our body’s defences remains a challenge. In this, theoretical models are crucial, to bridge the gap between species dynamics and underlying mechanisms and to develop analytic insight. Here we propose a replicator equation framework to model multispecies dynamics where an explicit notion of invasion resistance of a system emerges and can be studied explicitly. For illustration, we derive the conceptual link between such replicator equation and N microbial species’ growth and interaction traits, stemming from micro-scale environmental modification. Within this replicator framework, mean invasion fitness arises, evolves dynamically, and may undergo critical predictable shifts with global environmental changes. This mathematical approach clarifies the key role of this resident system trait for invader success, and highlights interaction principles among N species that optimize their collective resistance to invasion. We propose this model based on the replicator equation as a powerful new avenue to study, test and validate mechanisms of invasion resistance and colonization in multispecies microbial ecosystems and beyond.

Antibiotics found in and inspired by nature are life-saving cures for bacterial infections and have enabled modern medicine. However, the rise in resistance necessitates the discovery and development of novel antibiotics and alternative treatment strategies to prevent the return to a pre-antibiotic era. Once again, nature can serve as a source for new therapies in the form of natural product antibiotics and microbiota-based therapies. Screening of soil bacteria, particularly actinomycetes, identified most of the antibiotics used in the clinic today, but the rediscovery of existing molecules prompted a shift away from natural product discovery. Next-generation sequencing technologies and bioinformatics advances have revealed the untapped metabolic potential harbored within the genomes of environmental microbes. In this review, we first highlight current strategies for mining this untapped chemical space, including approaches to activate silent biosynthetic gene clusters and in situ culturing methods. Next, we describe how using live microbes in microbiota-based therapies can simultaneously leverage many of the diverse antimicrobial mechanisms found in nature to treat disease and the impressive efficacy of fecal microbiome transplantation and bacterial consortia on infection. Nature-provided antibiotics are some of the most important drugs in human history, and new technologies and approaches show that nature will continue to offer valuable inspiration for the next generation of antibacterial therapeutics. [ABSTRACT FROM AUTHOR]

Abstract Background The worldwide dissemination of extended spectrum beta-lactamase producing Enterobacteriales (ESBL-E) is of major concern. Microbiota may play a role in the host resistance to colonization with ESBL-E, but the underlying mechanisms remain unknown. We aimed to compare the gut microbiota composition between ESBL-producing E. coli or K. pneumoniae carriers and ESBL-E non-carriers according to the bacterial species. Results Among 255 patients included, 11 (4,3%) were colonized with ESBL-producing E. coli and 6 (2,4%) with ESBL-producing K. pneumoniae, which were compared with age- and sex-matched ESBL-E non carriers. While no significant differences were found between ESBL-producing E. coli carriers and non-carriers, gut bacteriobiota α-diversity was decreased in ESBL-K. pneumoniae faecal carriers compared both with non-carriers (p = 0.05), and with ESBL-producing E. coli carriers. The presence of Sellimonas intestinalis was associated with the absence of ESBL-producing E. coli fecal carriage. Campylobacter ureolyticus, Campylobacter hominis, bacteria belonging to Clostridium cluster XI and Saccharomyces sp. were associated with the absence of ESBL-producing K. pneumoniae faecal carriage. Conclusions The composition of the gut microbiota differs between ESBL-producing E. coli and K. pneumoniae faecal carriers suggesting that microbial species should be taken into account when investigating the role of gut microbiota in resistance to gut colonization with ESBL-E. Trial registration number: NCT04131569, date of registration: October 18, 2019.

Vibrio cholerae is a non-invasive enteric pathogen known to cause a major public health problem called cholera. The pathogen inhabits the aquatic environment while outside the human host, it is transmitted into the host easily through ingesting contaminated food and water containing the vibrios, thus causing diarrhoea and vomiting. V. cholerae must resist several layers of colonization resistance mechanisms derived from the host or the gut commensals to successfully survive, grow, and colonize the distal intestinal epithelium, thus causing an infection. The colonization resistance mechanisms derived from the host are not specific to V. cholerae but to all invading pathogens. However, some of the gut commensal-derived colonization resistance may be more specific to the pathogen, making it more challenging to overcome. Consequently, the pathogen has evolved well-coordinated mechanisms that sense and utilize the anti-colonization factors to modulate events that promote its survival and colonization in the gut. This review is aimed at discussing how V. cholerae interacts and resists both host- and microbe-specific colonization resistance mechanisms to cause infection.

Abstract Background The oral and colonic microbiota are distinct in healthy individuals. However, this distinction is diminished in common diseases such as colon cancer and inflammatory bowel disease, suggesting a potential pathogenic role for oral bacteria when ectopically colonized in the gut. A key mechanism for the segregation of oral and colonic microbiota niches is thought to be microbiota-mediated colonization resistance whereby the commensal gut microbiota outcompete and eliminate the ingested oral bacteria. Methods We tested this theory by analyzing exact amplicon sequence variants generated from concurrent fecal and oral samples from healthy volunteers exposed to a brief course of a single antibiotic (cohort 1), acute leukemia patients (cohort 2), and stem cell transplant recipients (cohort 3). Cohorts 2 and 3 represent extreme clinical scenarios with respect to antibiotic pressure and severity of gut microbiota injury. Results While mild antibiotic exposure in cohort 1 was not sufficient for colonization of any oral bacteria in the gut, even with extreme antibiotic pressure and severe gut microbiota disruptions in cohorts 2 and 3, only one oral species in each cohort colonized the gut. Conclusions Colonization resistance is dispensable for segregation of oral and colonic microbiota in humans. This finding implies that the presence of oral bacteria in the distal gut in diseases such as colon cancer and inflammatory bowel disease is not driven by impaired colonization resistance.

Simple Summary: Insects live in an incredibly complex environment and are constantly exposed to different microbiota, and some of them are beneficial while some are harmful to hosts. Colonization of some beneficial symbionts can increase host resistance against exogenous pathogens. This review summarizes the mechanisms by which symbionts contribute to the host's immune capacity. Adaptations of symbionts and their insect hosts to maintain such symbiotic relationships, and the significance of such relationships in the coevolution of symbiotic systems are also discussed to provide insights into the in-depth study of the contribution of symbionts to host physiology and behavior. The symbiotic microbiome is critical in promoting insect resistance against colonization by exogenous microorganisms. The mechanisms by which symbionts contribute to the host's immune capacity is referred to as colonization resistance. Symbionts can protect insects from exogenous pathogens through a variety of mechanisms, including upregulating the expression of host immune-related genes, producing antimicrobial substances, and competitively excluding pathogens. Concordantly, insects have evolved fine-tuned regulatory mechanisms to avoid overactive immune responses against symbionts or specialized cells to harbor symbionts. Alternatively, some symbionts have evolved special adaptations, such as the formation of biofilms to increase their tolerance to host immune responses. Here, we provide a review of the mechanisms about colonization resistance of symbionts in their insect hosts. Adaptations of symbionts and their insect hosts that may maintain such symbiotic relationships, and the significance of such relationships in the coevolution of symbiotic systems are also discussed to provide insights into the in-depth study of the contribution of symbionts to host physiology and behavior. [ABSTRACT FROM AUTHOR]

ABSTRACT The microbiota mediate multiple aspects of skin barrier function, including colonization resistance to pathogens such as Staphylococcus aureus. The endogenous skin microbiota limits S. aureus colonization via competition and direct inhibition. Novel mechanisms of colonization resistance are promising therapeutic targets for drug-resistant infections, such as those caused by methicillin-resistant S. aureus (MRSA). Here, we developed and characterized a swine model of topical microbiome perturbation and MRSA colonization. As in other model systems, topical antimicrobial treatment had a little discernable effect on community diversity though the overall microbial load was sensitive to multiple types of intervention, including swabbing. In parallel, we established a porcine skin culture collection and screened 7,700 isolates for MRSA inhibition. Using genomic and phenotypic criteria, we curated three isolates to investigate whether prophylactic colonization would inhibit MRSA colonization in vivo. The three-member consortium together, but not individually, provided protection against MRSA colonization, suggesting cooperation and/or synergy among the strains. Inhibitory isolates were represented across all major phyla of the pig skin microbiota and did not have a strong preference for inhibiting closely related species, suggesting that relatedness is not a condition of antagonism. These findings reveal the porcine skin as an underexplored reservoir of skin commensal species with the potential to prevent MRSA colonization and infection. IMPORTANCE The skin microbiota is protective against pathogens or opportunists such as S. aureus, the most common cause of skin and soft tissue infections. S. aureus can colonize normal skin and nasal passages, and colonization is a risk factor for infection, especially on breach of the skin barrier. Here, we established a pig model to study the competitive mechanisms of the skin microbiota and their role in preventing colonization by MRSA. This drug-resistant strain is also a livestock pathogen, and swine herds can be reservoirs of MRSA carriage. From 7,700 cultured skin isolates, we identified 37 unique species across three phyla that inhibited MRSA. A synthetic community of three inhibitory isolates provided protection together, but not individually, in vivo in a murine model of MRSA colonization. These findings suggest that antagonism is widespread in the pig skin microbiota, and these competitive interactions may be exploited to prevent MRSA colonization.

Background: The worldwide dissemination of extended spectrum beta-lactamase producing Enterobacteriales (ESBL-E) is of major concern. Microbiota may play a role in the host resistance to colonization with ESBL-E, but the underlying mechanisms remain unknown. We aimed to compare the gut microbiota composition between ESBL-producing E. coli or K. pneumoniae carriers and ESBL-E non-carriers according to the bacterial species. Results: Among 255 patients included, 11 (4,3%) were colonized with ESBL-producing E. coli and 6 (2,4%) with ESBL-producing K. pneumoniae, which were compared with age- and sex-matched ESBL-E non carriers. While no significant differences were found between ESBL-producing E. coli carriers and non-carriers, gut bacteriobiota α-diversity was decreased in ESBL-K. pneumoniae faecal carriers compared both with non-carriers (p = 0.05), and with ESBL-producing E. coli carriers. The presence of Sellimonas intestinalis was associated with the absence of ESBL-producing E. coli fecal carriage. Campylobacter ureolyticus, Campylobacter hominis, bacteria belonging to Clostridium cluster XI and Saccharomyces sp. were associated with the absence of ESBL-producing K. pneumoniae faecal carriage. Conclusions: The composition of the gut microbiota differs between ESBL-producing E. coli and K. pneumoniae faecal carriers suggesting that microbial species should be taken into account when investigating the role of gut microbiota in resistance to gut colonization with ESBL-E. Trial registration number: NCT04131569, date of registration: October 18, 2019. [ABSTRACT FROM AUTHOR]

Vibrio cholerae is a non-invasive enteric pathogen known to cause a major public health problem called cholera. The pathogen inhabits the aquatic environment while outside the human host, it is transmitted into the host easily through ingesting contaminated food and water containing the vibrios, thus causing diarrhoea and vomiting. V. cholerae must resist several layers of colonization resistance mechanisms derived from the host or the gut commensals to successfully survive, grow, and colonize the distal intestinal epithelium, thus causing an infection. The colonization resistance mechanisms derived from the host are not specific to V. cholerae but to all invading pathogens. However, some of the gut commensal-derived colonization resistance may be more specific to the pathogen, making it more challenging to overcome. Consequently, the pathogen has evolved wellcoordinated mechanisms that sense and utilize the anti-colonization factors to modulate events that promote its survival and colonization in the gut. This review is aimed at discussing how V. cholerae interacts and resists both host- and microbe-specific colonization resistance mechanisms to cause infection. [ABSTRACT FROM AUTHOR]

Gut microbiota‐mediated colonization resistance (CR) is crucial in protecting the host from intestinal infections. Sleep deprivation (SD) is an important contributor in the disturbances of intestinal homeostasis. However, whether and how SD affects host CR remains largely unknown. Here, it is shown that SD impairs intestinal CR in mice, whereas nicotinamide mononucleotide (NMN) supplementation restores it. Microbial diversity and metabolomic analyses suggest that gut microbiota and metabolite profiles in SD‐treated mice are highly shaped, whereas NMN reprograms these differences. Specifically, the altered gut microbiota in SD mice further incurs the disorder of secondary bile acids pool accompanied by a decrease in deoxycholic acid (DCA). Conversely, NMN supplementation retakes the potential benefits of DCA, which is associated with specific gut microbiota involved in primary bile acids metabolic flux. In animal models of infection, DCA is effective in preventing and treating bacterial infections when used alone or in combination with antibiotics. Mechanistically, DCA alone disrupts membrane permeability and aggravates oxidative damage, thereby reducing intestinal pathogen burden. Meanwhile, exogenous DCA promotes antibiotic accumulation and destroys oxidant–antioxidant system, thus potentiating antibiotic efficacy. Overall, this work highlights the important roles of gut microbiota and bile acid metabolism in the maintenance of intestinal CR. [ABSTRACT FROM AUTHOR]

Background: The oral and colonic microbiota are distinct in healthy individuals. However, this distinction is diminished in common diseases such as colon cancer and inflammatory bowel disease, suggesting a potential pathogenic role for oral bacteria when ectopically colonized in the gut. A key mechanism for the segregation of oral and colonic microbiota niches is thought to be microbiota-mediated colonization resistance whereby the commensal gut microbiota outcompete and eliminate the ingested oral bacteria. Methods: We tested this theory by analyzing exact amplicon sequence variants generated from concurrent fecal and oral samples from healthy volunteers exposed to a brief course of a single antibiotic (cohort 1), acute leukemia patients (cohort 2), and stem cell transplant recipients (cohort 3). Cohorts 2 and 3 represent extreme clinical scenarios with respect to antibiotic pressure and severity of gut microbiota injury. Results: While mild antibiotic exposure in cohort 1 was not sufficient for colonization of any oral bacteria in the gut, even with extreme antibiotic pressure and severe gut microbiota disruptions in cohorts 2 and 3, only one oral species in each cohort colonized the gut. Conclusions: Colonization resistance is dispensable for segregation of oral and colonic microbiota in humans. This finding implies that the presence of oral bacteria in the distal gut in diseases such as colon cancer and inflammatory bowel disease is not driven by impaired colonization resistance. [ABSTRACT FROM AUTHOR]

Avian malaria infection has been known to affect host microbiota, but the impact of Plasmodium infection on the colonization resistance in bird gut microbiota remains unexplored. This study investigated the dynamics of Plasmodium relictum infection in canaries, aiming to explore the hypothesis that microbiota modulation by P. relictum would reduce colonization resistance. Canaries were infected with P. relictum, while a control group was maintained. The results revealed the presence of P. relictum in the blood of all infected canaries. Analysis of the host microbiota showed no significant differences in alpha diversity metrics between infected and control groups. However, significant differences in beta diversity indicated alterations in the microbial taxa composition of infected birds. Differential abundance analysis identified specific taxa with varying prevalence between infected and control groups at different time points. Network analysis demonstrated a decrease in correlations and revealed that P. relictum infection compromised the bird microbiota’s ability to resist the removal of taxa but did not affect network robustness with the addition of new nodes. These findings suggest that P. relictum infection reduces gut microbiota stability and has an impact on colonization resistance. Understanding these interactions is crucial for developing strategies to enhance colonization resistance and maintain host health in the face of parasitic infections.

Antibiotic resistance is currently one of the greatest threats to human health. Widespread use and residues of antibiotics in humans, animals, and the environment can exert selective pressure on antibiotic resistance bacteria (ARB) and antibiotic resistance gene (ARG), accelerating the flow of antibiotic resistance. As ARG spreads to the population, the burden of antibiotic resistance in humans increases, which may have potential health effects on people. Therefore, it is critical to mitigate the spread of antibiotic resistance to humans and reduce the load of antibiotic resistance in humans. This review briefly described the information of global antibiotic consumption information and national action plans (NAPs) to combat antibiotic resistance and provided a set of feasible control strategies for the transmission of ARB and ARG to humans in three areas including (a) Reducing the colonization capacity of exogenous ARB, (b) Enhancing human colonization resistance and mitigating the horizontal gene transfer (HGT) of ARG, (c) Reversing ARB antibiotic resistance. With the hope of achieving interdisciplinary one-health prevention and control of bacterial resistance.

Metabolic labeling with clickable noncanonical amino acids has enabled nascent proteome profiling, which can be performed in a cell‐type‐specific manner. However, nascent proteomics in an intercellular communication‐dependent manner remains challenging. Here we develop communication‐activated profiling of protein expression (CAPPEX), which integrates the LuxI/LuxR quorum sensing circuit with the cell‐type‐specific nascent proteomics method to enable selective click‐labeling of newly synthesized proteins in a specific bacterium upon receiving chemical signals from another reporter bacterium. CAPPEX reveals that E. coli competes with Salmonella for tryptophan as the precursor for indole, and the resulting indole suppressed the expression of virulence factors in Salmonella. This tryptophan‐indole axis confers attenuation of Salmonella invasion in host cells and living mice. The CAPPEX strategy should be widely applicable for investigating various interbacterial communication processes. [ABSTRACT FROM AUTHOR]

The gut microbiota of honeybees is highly diverse at the strain level and essential to the proper function and development of the host. Interactions between the host and its gut microbiota, such as specific microbes regulating the innate immune system, protect the host against pathogen infections. However, little is known about the capacity of these strains deposited in one colony to inhibit pathogens. In this study, we assembled a defined microbial community based on phylogeny analysis, the ‘Core-20’ community, consisting of 20 strains isolated from the honeybee intestine. The Core-20 community could trigger the upregulation of immune gene expressions and reduce Hafnia alvei prevalence, indicating immune priming underlies the microbial protective effect. Functions related to carbohydrate utilization and the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS systems) are represented in genomic analysis of the defined community, which might be involved in manipulating immune responses. Additionally, we found that the defined Core-20 community is able to colonize the honeybee gut stably through passages. In conclusion, our findings highlight that the synthetic gut microbiota could offer protection by regulating the host immune system, suggesting that the strain collection can yield insights into host-microbiota interactions and provide solutions to protect honeybees from pathogen infections. [ABSTRACT FROM AUTHOR]