Search

This study examined the effectiveness of the Carolina College Advising Corps (CCAC) on two college readiness outcomes: advanced college preparatory course enrollment and SAT test-taking behaviors. The focus of this study is on concrete college readiness measures beyond mere college aspirations, as these measures more accurately predict college success. We utilized a difference-in-differences research design, which compares treatment and comparison schools over time using pre- and post-intervention panel data. The treatment group consisted of partner high schools in North Carolina that received the CCAC treatment, and the comparison group included public schools in the state that do not have this resource. We found that the introduction of a CCAC adviser increased schools' SAT participation rate but lowered their overall average score. The results of this work add to the growing literature on the impact of college advising professionals and may help inform goal-setting for the CCAC and similar interventions.

ABSTRACTEmerging evidence indicates that antibiotic-induced dysbiosis can play an etiological role in the pathogenesis of neuropsychiatric disorders. However, most of this evidence comes from rodent models. The objective of this study was to evaluate if antibiotic-induced gut dysbiosis can elicit changes in gut metabolites and behavior indicative of gut-brain axis disruption in common marmosets (Callithrix jacchus) – a nonhuman primate model often used to study sociability and stress. We were able to successfully induce dysbiosis in marmosets using a custom antibiotic cocktail (vancomycin, enrofloxacin and neomycin) administered orally for 28 days. This gut dysbiosis altered gut metabolite profiles, behavior, and stress reactivity. Increase in gut Fusobacterium spp. post-antibiotic administration was a novel dysbiotic response and has not been observed in any rodent or human studies to date. There were significant changes in concentrations of several gut metabolites which are either neurotransmitters (e.g., GABA and serotonin) or have been found to be moderators of gut-brain axis communication in rodent models (e.g., short-chain fatty acids and bile acids). There was an increase in affiliative behavior and sociability in antibiotic-administered marmosets, which might be a coping mechanism in response to gut dysbiosis-induced stress. Increase in urinary cortisol levels after multiple stressors provides more definitive proof that this model of dysbiosis may cause disrupted communication between gut and brain in common marmosets. This study is a first attempt to establish common marmosets as a novel model to study the impact of severe gut dysbiosis on gut-brain axis cross-talk and behavior.

Initial urologic management of pediatric neurogenic lower urinary tract dysfunction (NLUTD) includes clean intermittent catheterization (CIC) regimen and use of anticholinergic or beta3 agonist medications. Historically, NLUTD that did not respond to these initial management strategies received open surgical procedures such as augmentation cystoplasty (AC) to increase bladder capacity and create a lower-pressure reservoir. Since its first reported use in 2002, intradetrusor onabotulinumtoxinA (BTX-A) injections has developed an emerging role in management of pediatric NLUTD, culminating in its recent FDA-approval in 2021. In this review, the current evidence regarding the safety, tolerability, and efficacy of BTX-A use in pediatric NLUTD will be summarized. Additionally, we will attempt to define the current role of BTX-A in the management of patients with NLUTD, discuss limitations to the current body of literature, and suggest future avenues of study.

Abstract The urinary bladder harbors a community of microbes termed the urobiome, which remains understudied. In this study, we present the urobiome of healthy infant males from samples collected by transurethral catheterization. Using a combination of enhanced culture and amplicon sequencing, we identify several common bacterial genera that can be further investigated for their effects on urinary health across the lifespan. Many genera were shared between all samples suggesting a consistent urobiome composition among this cohort. We note that, for this cohort, early life exposures including mode of birth (vaginal vs. Cesarean section), or prior antibiotic exposure did not influence urobiome composition. In addition, we report the isolation of culturable bacteria from the bladders of these infant males, including Actinotignum spp., a bacterial genus that has been associated with urinary tract infections in older male adults. Herein, we isolate and sequence 9 distinct strains of Actinotignum spp. enhancing the genomic knowledge surrounding this genus and opening avenues for delineating the microbiology of this urobiome constituent. Furthermore, we present a framework for using the combination of culture-dependent and sequencing methodologies for uncovering mechanisms in the urobiome.

There are previous epidemiological studies reporting associations between antibiotic use and psychiatric symptoms. Antibiotic-induced gut dysbiosis and alteration of microbiota-gut-brain axis communication has been proposed to play a role in this association. In this systematic review and meta-analysis, we reviewed published articles that have presented results on changes in cognition, emotion, and behavior in rodents (rats and mice) after antibiotic-induced gut dysbiosis. We searched three databases—PubMed, Web of Science, and SCOPUS to identify such articles using dedicated search strings and extracted data from 48 articles. Increase in anxiety and depression-like behavior was reported in 32.7 and 40.7 percent of the study-populations, respectively. Decrease in sociability, social novelty preference, recognition memory and spatial cognition was found in 18.1, 35.3, 26.1, and 62.5 percent of the study-populations, respectively. Only one bacterial taxon (increase in gut Proteobacteria) showed statistically significant association with behavioral changes (increase in anxiety). There were no consistent findings with statistical significance for the potential biomarkers [Brain-derived neurotrophic factor (BDNF) expression in the hippocampus, serum corticosterone and circulating IL-6 and IL-1β levels]. Results of the meta-analysis revealed a significant association between symptoms of negative valence system (including anxiety and depression) and cognitive system (decreased spatial cognition) with antibiotic intake (p

Abstract The gut microbiome of primates is known to be influenced by both host genetic background and subsistence strategy. However, these inferences have been made mainly based on adaptations in bacterial composition - the bacteriome and have commonly overlooked the fungal fraction - the mycobiome. To further understand the factors that shape the gut mycobiome of primates and mycobiome-bacteriome interactions, we sequenced 16 S rRNA and ITS2 markers in fecal samples of four different nonhuman primate species and three human groups under different subsistence patterns (n = 149). The results show that gut mycobiome composition in primates is still largely unknown but highly plastic and weakly structured by primate phylogeny, compared with the bacteriome. We find significant gut mycobiome overlap between captive apes and human populations living under industrialized subsistence contexts; this is in contrast with contemporary hunter-gatherers and agriculturalists, who share more mycobiome traits with diverse wild-ranging nonhuman primates. In addition, mycobiome-bacteriome interactions were specific to each population, revealing that individual, lifestyle and intrinsic ecological factors affect structural correspondence, number, and kind of interactions between gut bacteria and fungi in primates. Our findings indicate a dominant effect of ecological niche, environmental factors, and diet over the phylogenetic background of the host, in shaping gut mycobiome composition and mycobiome-bacteriome interactions in primates.

Abstract Background Intrabolus pressure (IBP) recorded by high-resolution manometry (HRM) portrays the compartmentalized force on a bolus during esophageal peristalsis. HRM may be a reliable screening tool for esophageal dysmotility in patients with elevated average maximum IBP (AM-IBP). Timed barium esophagram (TBE) is a validated measure of esophageal emptying disorders, such as esophagogastric junction outflow obstruction and achalasia. This study aimed to determine if an elevated AM-IBP correlates with esophageal dysmotility on HRM and/or delayed esophageal emptying on TBE. Methods A retrospective analysis of all HRM (unweighted sample n = 155) performed at a tertiary referral center from 09/2015–03/2017 yielded a case group (n = 114) with abnormal AM-IBP and a control group (n = 41) with a normal AM-IBP (pressure

Abstract Background and Aim This review investigates the role of gastrointestinal and hepatic manifestations in COVID‐19, particularly with regard to the prevalence of isolated gastrointestinal (GI) symptoms. Methods We searched PubMed, Embase, and Cochrane library for COVID‐19 publications from 1 December 2019 to 18 May 2020. We included any study that reported the presence of GI symptoms in a sample of >5 COVID‐19 patients. Data collection and risk of bias assessment were performed independently by two reviewers. Where ≥3 studies reported data sufficiently similar to allow calculation of a pooled prevalence, we performed random effects meta‐analysis. Results This review included 17 776 COVID‐19 patients from 108 studies. Isolated GI symptoms only occurred in 1% (95% confidence interval [CI] 0–6%) of patients. GI symptoms were reported in 20% (95% CI 15–24%) of patients. The most common were anorexia (21%, 95% CI 15–27%), diarrhea (13%, 95% CI 11–16%), nausea or vomiting (8%, 95% CI 6–11%), and abdominal pain (4%, 95% CI 2–6%). Transaminase elevations were present in 24% (95% CI 17–31%) of patients. Higher prevalence of GI symptoms were reported in studies published after 1st April, with prevalence of diarrhea 16% (95% CI 13–20), nausea or vomiting 12% (95% CI 8–16%), and any GI symptoms 24% (95% CI 18–34%). GI symptoms were associated with severe COVID‐19 disease (odds ratio [OR] 2.1, 95% CI 1.3–3.2), but not mortality (OR 0.90, 95% CI 0.52–1.54). Conclusions Patients with isolated GI symptoms may represent a small but significant portion of COVID‐19 cases. When testing resources are abundant, clinicians should still consider testing patients with isolated GI symptoms or unexplained transaminase elevations for COVID‐19. More recent studies estimate higher overall GI involvement in COVID‐19 than was previously recognized.

Abstract Background Combining impedance with pH monitoring improves the detection and characterization of gastro-oesophageal reflux (GOR), yet the two modalities frequently differ in GOR quantification. Ambulatory 24-h pH-impedance monitoring often reveals more significant oesophageal acid exposure than impedance-measured reflux activity in patients with symptomatic gastro-oesophageal reflux disease (GORD). The purpose of this study is to elucidate the discrepancies between these modalities by assessing the predictive accuracy of impedance compared to acid exposure standards. Methods A single-institution, retrospective review of sequential 24-h pH-impedance results of 72 patients with symptomatic GOR off anti-secretory therapy was conducted. Reflux events measured by impedance were stratified by patient position and compared to oesophageal acid exposure time (AET). Oesophageal AET limits for GORD detection were utilized as gold standards to generate serial receiver operator characteristics (ROC) curves to assess the sensitivity and specificity of current impedance GORD detection limits and identify optimized impedance standards based on area under the curve (AUC) analysis. Results Mean total AET time was 10.5% (± 9.9%), and 63.8% of patients had elevated AET. By impedance, median GOR frequency was 43 (IQR 21–68), and 22.2% exceeded conventional GOR frequency limits of normal. ROC curve analysis revealed the current impedance standard of > 73 GOR events has a sensitivity of 32.6% and specificity of 96.5% (AUC 0.74) for GORD detection. By AUC analysis, an impedance threshold of > 41 GOR events is optimal for GORD detection (sensitivity 69.6%, specificity 80.7%, AUC 0.83). Conclusion Conventional impedance standards for abnormal GOR frequency are weakly sensitive for the detection of GORD, providing a possible explanation to discrepancies in AET and impedance interpretation. Lowering impedance-measured GOR frequency limits to > 41 optimizes sensitivity and specificity while increasing congruence between pH and impedance metrics.

Abstract Background The gut microbiome harbors trillions of bacteria that play a major role in dietary nutrient extraction and host metabolism. Metabolic diseases such as obesity and diabetes are associated with shifts in microbiome composition and have been on the rise in Westernized or highly industrialized countries. At the same time, Westernized diets low in dietary fiber have been shown to cause loss of gut microbial diversity. However, the link between microbiome composition, loss of dietary fiber, and obesity has not been well defined. Results To study the interactions between gut microbiota, dietary fiber, and weight gain, we transplanted captive and wild douc gut microbiota into germ-free mice and then exposed them to either a high- or low-fiber diet. The group receiving captive douc microbiota gained significantly more weight, regardless of diet, while mice receiving a high-fiber diet and wild douc microbiota remained lean. In the presence of a low-fiber diet, the wild douc microbiota partially prevented weight gain. Using 16S rRNA gene amplicon sequencing we identified key bacterial taxa in each group, specifically a high relative abundance of Bacteroides and Akkermansia in captive douc FMT mice and a higher relative abundance of Lactobacillus and Clostridium in the wild douc FMT mice. Conclusions In the context of our germ-free mouse experiment, wild douc microbiota could serve as a reservoir for microbes for cross-species transplants. Our results suggest that wild douc microbiota are tailored to diverse fiber diets and can prevent weight gain when exposed to a native diet. Graphical abstract

The conditions under which social media use impacts well-being and mental health are complex. The current 10-day longitudinal quasi-experiment (student sample, N = 111) applied an entertainment theory lens to explore the effects of active posting and engaging with hedonic or inspiring Facebook content (vs. passive browsing) on young people’s eudaimonic well-being (levels of connectedness to humanity, love, compassion, presence of meaning) and mental health (anxiety and depressive symptoms). The results provide tentative evidence that finding and sharing inspiring content to a Facebook group increased love and compassion toward others over time. It also led to more compassion at the end of the study compared to participants who shared hedonic content. Although we did not find an increase in connectedness and meaningfulness over time for participants sharing content that they found inspiring, the latter also did not take away from those experiences, regardless of how they used it. Similarly, no decrease—but also no increase—in anxiety and depressive symptoms were found over time, regardless of condition. The study stresses the importance of better understanding the content young adults engage with on social media for their mental health and well-being.

The social facilitation of eating plays a significant role in influencing individuals’ eating decisions. However, how social eating cues are processed in health promotion messages is unclear. This study examined individuals’ food craving in response to social cues in images (Experiment 1) and emotional experiences, perceived threat, perceived efficacy, behavioral intentions, and motivational coactivation elicited by social eating cues in obesity prevention fear appeals (Experiment 2). Results suggested that the presence of a group of people eating in an image facilitated food craving for the presented foods. Moreover, fear appeals that presented obesity and its consequences with more social eating cues, versus individual eating cues, generated greater positive emotional responses, perceived threat severity, response and self-efficacy, and motivational coactivation indicating more attention and threat vigilance. However, these cues also generated fewer self-reported intentions to change unhealthy eating behaviors. Implications and suggestions for future research are discussed.

The lemurs of Madagascar include numerous species characterized by folivory across several families. Many extant lemuriform folivores exist in sympatry in Madagascar’s remaining forests. These species avoid feeding competition by adopting different dietary strategies within folivory, reflected in behavioral, morphological, and microbiota diversity across species. These conditions make lemurs an ideal study system for understanding adaptation to leaf-eating. Most folivorous lemurs are also highly endangered. The significance of folivory for conservation outlook is complex. Though generalist folivores may be relatively well equipped to survive habitat disturbance, specialist folivores occupying narrow dietary niches may be less resilient. Characterizing the genetic bases of adaptation to folivory across species and lineages can provide insights into their differential physiology and potential to resist habitat change. We recently reported accelerated genetic change in RNASE1, a gene encoding an enzyme (RNase 1) involved in molecular adaptation in mammalian folivores, including various monkeys and sifakas (genus Propithecus; family Indriidae). Here, we sought to assess whether other lemurs, including phylogenetically and ecologically diverse folivores, might show parallel adaptive change in RNASE1 that could underlie a capacity for efficient folivory. We characterized RNASE1 in 21 lemur species representing all five families and members of the three extant folivorous lineages: (1) bamboo lemurs (family Lemuridae), (2) sportive lemurs (family Lepilemuridae), and (3) indriids (family Indriidae). We found pervasive sequence change in RNASE1 across all indriids, a dN/dS value > 3 in this clade, and evidence for shared change in isoelectric point, indicating altered enzymatic function. Sportive and bamboo lemurs, in contrast, showed more modest sequence change. The greater change in indriids may reflect a shared strategy emphasizing complex gut morphology and microbiota to facilitate folivory. This case study illustrates how genetic analysis may reveal differences in functional traits that could influence species’ ecology and, in turn, their resilience to habitat change. Moreover, our results support the body of work demonstrating that not all primate folivores are built the same and reiterate the need to avoid generalizations about dietary guild in considering conservation outlook, particularly in lemurs where such diversity in folivory has probably led to extensive specialization via niche partitioning.

Abstract Background Colonoscopy requires colon cleansing. For this, many polyethylene glycol (PEG)-based preparations still require a high preparation-volume intake. Using an increased osmotic load with ascorbate (Asc), five new low-volume PEG-based bowel preparations (LVPEG) were tested for clinical proof of concept. Methods This two-part, open-label study examined preparation-volumes of 1–1.25 L and total required fluid volumes of 2–3 L. Part 1, in healthy volunteers, used mean cumulative 24-h stool weight (target > 2750 g) to identify a lead candidate. Part 2 was endoscopist-blinded: patients undergoing screening colonoscopy were randomized before treatment with the selected lead, one of two variants of it, or the control 2 L PEG + Asc. Two primary endpoints were used for proof of concept demonstration: mean 24-h stool weight and bowel cleansing success (Harefield Cleansing Scale). Results A total of 120 subjects (30 per group) were enrolled/randomized 1:1:1:1 (max 40:60 gender ratio) per completed Part. In Part 1, LVPEG-3 achieved the largest mean stool weight (3399 g: P

Vast numbers of microorganisms inhabit the mammalian gastrointestinal tract in a complex community referred to as the gut microbiome. An individual’s microbiome may be impacted by genetics, diet, and various environmental factors, and has been associated with many health states and diseases, though specific explanations are lacking. While these communities are well-studied in human populations, non-human primates (NHPs), in particular zoo-resident or captive NHPs, offer distinct advantages to increasing our understanding of factors that influence gut microbiome composition. Here, we characterize the gut microbiome composition of a phylogenetically diverse cohort of NHPs residing in the same urban zoo. We show that despite overlapping and controlled environmental contexts, gut microbiomes are still distinguished between NHP host species. However, when comparing the zoo cohort to wild NHPs, we show that captivity status strongly distinguishes zoo-resident NHPs from their wild counterparts, regardless of host phylogeny. Microbial orders unique to captive NHPs include taxa commonly present in human gut microbiomes. Together, these results demonstrate that differences between NHP species are strongly associated with gut microbiome composition and diversity, suggesting that species-specific approaches should be considered when investigating environmental factors’ influence on gut microbiome composition.

Childhood obesity is a serious public health problem worldwide. Perturbations in the gut microbiota composition have been associated with the development of obesity in both children and adults. Probiotics, on the other hand, are proven to restore the composition of the gut microbiome which helps reduce the development of obesity. However, data on the effect of probiotics on gut microbiota and its association with childhood obesity is limited. This study aims to determine the effect of probiotics supplement intervention on gut microbiota profiles in obese and normal-weight children. A total of 37 children, 17 normal weight, and 20 overweight school children from a government school in Selangor were selected to participate in this study. Participants were further divided into intervention and control groups. The intervention groups received daily probiotic drinks while the control groups continued eating their typical diet. Fecal samples were collected from the participants for DNA extraction. The hypervariable V3 and V4 regions of 16S rRNA gene were amplified and sequenced using the Illumina MiSeq platform. No significant differences in alpha diversity were observed between normal weight and obese children in terms of the Shannon Index for evenness or species richness. However, a higher intervention effect on alpha diversity was observed among normal-weight participants compared to obese. The participants’ microbiome was found to fluctuate throughout the study. Analysis of the taxa at species level showed an increase in Bacteroides ovatus among the normal weight cohort. Genus-level comparison revealed a rise in genus Lachnospira and Ruminococcus in the overweight participants after intervention, compared to the normal-weight participants. The probiotics intervention causes an alteration in gut microbiota composition in both normal and overweight children. Though the association could not be defined statistically, this study has provided an improved understanding of the intervention effect of probiotics on gut microbiome dysbiosis in an underrepresented population.

ABSTRACT Fluoroquinolones and cephalosporins are critically important antimicrobial classes for both human and veterinary medicine. We previously found a drastic increase in enrofloxacin resistance in clinical Escherichia coli isolates collected from diseased pigs from the United States over 10 years (2006 to 2016). However, the genetic determinants responsible for this increase have yet to be determined. The aim of the present study was to identify and characterize the genetic basis of resistance against fluoroquinolones (enrofloxacin) and extended-spectrum cephalosporins (ceftiofur) in swine E. coli isolates using whole-genome sequencing (WGS). blaCMY-2 (carried by IncA/C2, IncI1, and IncI2 plasmids), blaCTX-M (carried by IncF, IncHI2, and IncN plasmids), and blaSHV-12 (carried by IncHI2 plasmids) genes were present in 87 (82.1%), 19 (17.9%), and 3 (2.83%) of the 106 ceftiofur-resistant isolates, respectively. Of the 110 enrofloxacin-resistant isolates, 90 (81.8%) had chromosomal mutations in gyrA, gyrB, parA, and parC genes. Plasmid-mediated quinolone resistance genes [qnrB77, qnrB2, qnrS1, qnrS2, and aac-(6)-lb′-cr] borne on ColE, IncQ2, IncN, IncF, and IncHI2 plasmids were present in 24 (21.8%) of the enrofloxacin-resistant isolates. Virulent IncF plasmids present in swine E. coli isolates were highly similar to epidemic plasmids identified globally. High-risk E. coli clones, such as ST744, ST457, ST131, ST69, ST10, ST73, ST410, ST12, ST127, ST167, ST58, ST88, ST617, ST23, etc., were also found in the U.S. swine population. Additionally, the colistin resistance gene (mcr-9) was present in several isolates. This study adds valuable information regarding resistance to critical antimicrobials with implications for both animal and human health. IMPORTANCE Understanding the genetic mechanisms conferring resistance is critical to design informed control and preventive measures, particularly when involving critically important antimicrobial classes such as extended-spectrum cephalosporins and fluoroquinolones. The genetic determinants of extended-spectrum cephalosporin and fluoroquinolone resistance were highly diverse, with multiple plasmids, insertion sequences, and genes playing key roles in mediating resistance in swine Escherichia coli. Plasmids assembled in this study are known to be disseminated globally in both human and animal populations and environmental samples, and E. coli in pigs might be part of a global reservoir of key antimicrobial resistance (AMR) elements. Virulent plasmids found in this study have been shown to confer fitness advantages to pathogenic E. coli strains. The presence of international, high-risk zoonotic clones provides worrisome evidence that resistance in swine isolates may have indirect public health implications, and the swine population as a reservoir for these high-risk clones should be continuously monitored.

This article provides a reusable dataset describing detailed phenotypic and associated clinical parameters in n=303 clinical isolates of urinary Escherichia coli collected at Vanderbilt University Medical Center. De-identified clinical data collected with each isolate are detailed here and correlated to biofilm abundance and metabolomics data. Biofilm-abundance data were collected for each isolate under different in vitro conditions along with datasets quantifying biofilm abundance of each isolate under different conditions. Metabolomics data were collected from a subset of bacterial strains isolated from uncomplicated cases of cystitis or cases with no apparent symptoms accompanying colonization. For more insight, please see “Defining a Molecular Signature for Uropathogenic versus Urocolonizing Escherichia coli: The Status of the Field and New Clinical Opportunities” [1].

ABSTRACT Social behavior can alter the microbiome composition via transmission among social partners, but there have been few controlled experimental studies of gut microbiome transmission among social partners in primates. We collected longitudinal fecal samples from eight unrelated male-female pairs of marmoset monkeys prior to pairing and for 8 weeks following pairing. We then sequenced 16S rRNA to characterize the changes in the gut microbiome that resulted from the pairing. Marmoset pairs had a higher similarity in gut microbiome communities after pairing than before pairing. We discovered sex differences in the degrees of change in gut microbiome communities following pairing. Specifically, the gut microbiome communities in males exhibited greater dissimilarity from the prepairing stage (baseline) than the gut microbiome communities in females. Conversely, females showed a gradual stabilization in the rate of the gut microbiome community turnover. Importantly, we found that the male fecal samples harbored more female-source gut microbes after pairing, especially early in pairing (paired test, P

The last few decades have seen an outpouring of gastrointestinal (GI) microbiome studies across diverse host species. Studies have ranged from assessments of GI microbial richness and diversity to classification of novel microbial lineages. Assessments of the “normal” state of the GI microbiome composition across multiple host species has gained increasing importance for distinguishing healthy versus diseased states. This study aimed to determine baselines and trends over time to establish “typical” patterns of GI microbial richness and diversity, as well as inter-individual variation, in three populations of western lowland gorillas (Gorilla gorilla gorilla) under human care at three zoological institutions in North America. Fecal samples were collected from 19 western lowland gorillas every two weeks for seven months (n = 248). Host identity and host institution significantly affected GI microbiome community composition (p < 0.05), although host identity had the most consistent and significant effect on richness (p = 0.03) and Shannon diversity (p = 0.004) across institutions. Significant changes in microbial abundance over time were observed only at Denver Zoo (p < 0.05). Our results suggest that individuality contributes to most of the observed GI microbiome variation in the study populations. Our results also showed no significant changes in any individual’s microbial richness or Shannon diversity during the 7-month study period. While some microbial taxa (Prevotella, Prevotellaceae and Ruminococcaceae) were detected in all gorillas at varying levels, determining individual baselines for microbial composition comparisons may be the most useful diagnostic tool for optimizing non-human primate health under human care.

ABSTRACT The microbiome is important to all animals, including poultry, playing a critical role in health and performance. Low-dose antibiotics have historically been used to modulate food production animals and their microbiome. Identifying alternatives to antibiotics conferring similar modulatory properties has been elusive. The purpose of this study was to determine if a host-tailored probiotic could recapitulate effects of a low-dose antibiotic on host response and the developing microbiome. Over 13 days of life, turkey poults were supplemented continuously with a low-dose antibiotic or oral supplementation of a prebiotic with or without two different probiotics (8 cage units, n = 80 per group). Gastrointestinal bacterial and fungal communities of poults were characterized by 16S rRNA gene and ITS2 amplicon sequencing. Localized and systemic host gene expression was assessed using transcriptome sequencing (RNA-Seq), kinase activity was assessed by avian-specific kinome peptide arrays, and performance parameters were assessed. We found that development of the early-life microbiome of turkey poults was tightly ordered in a tissue- and time-specific manner. Low-dose antibiotic and turkey-tailored probiotic supplementation, but not nontailored probiotic supplementation, elicited similar shifts in overall microbiome composition during development compared to controls. Treatment-induced bacterial changes were accompanied by parallel shifts in the fungal community and host gene expression and enhanced performance metrics. These results were validated in pen trials that identified further additive effects of the turkey-tailored probiotic combined with different prebiotics. Alternative approaches to low-dose antibiotic use in poultry are feasible and can be optimized utilizing the indigenous poultry microbiome. Similar approaches may also be beneficial for humans. IMPORTANCE Alternative approaches are greatly needed to reduce the need for antibiotic use in food animal production. This study utilized a pipeline for the development of a host-tailored probiotic to enhance performance in commercial turkeys and modulate their microbiota, similar to the effects of low-dose antibiotic administration. We determined that a host-tailored probiotic, developed in the context of the commercial turkey gut microbiome, was more effective at modulating these parameters than a nontailored probiotic cocktail. Furthermore, the host-tailored probiotic mimicked many of the effects of a low-dose antibiotic growth promoter. Surprisingly, the effects of the antibiotic growth promoter and host-tailored probiotic were observed across kingdoms, illustrating the coordinated interkingdom effects of these approaches. This work suggests that tailored approaches to probiotic development hold promise for modulating the avian host and its microbiota.

ABSTRACT Biofilms are multicellular bacterial communities encased in a self-secreted extracellular matrix comprised of polysaccharides, proteinaceous fibers, and DNA. Organization of these components lends spatial organization to the biofilm community such that biofilm residents can benefit from the production of common goods while being protected from exogenous insults. Spatial organization is driven by the presence of chemical gradients, such as oxygen. Here we show that two quinol oxidases found in Escherichia coli and other bacteria organize along the biofilm oxygen gradient and that this spatially coordinated expression controls architectural integrity. Cytochrome bd, a high-affinity quinol oxidase required for aerobic respiration under hypoxic conditions, is the most abundantly expressed respiratory complex in the biofilm community. Depletion of the cytochrome bd-expressing subpopulation compromises biofilm complexity by reducing the abundance of secreted extracellular matrix as well as increasing cellular sensitivity to exogenous stresses. Interrogation of the distribution of quinol oxidases in the planktonic state revealed that ∼15% of the population expresses cytochrome bd at atmospheric oxygen concentration, and this population dominates during acute urinary tract infection. These data point toward a bet-hedging mechanism in which heterogeneous expression of respiratory complexes ensures respiratory plasticity of E. coli across diverse host niches. IMPORTANCE Biofilms are multicellular bacterial communities encased in a self-secreted extracellular matrix comprised of polysaccharides, proteinaceous fibers, and DNA. Organization of these components lends spatial organization in the biofilm community. Here we demonstrate that oxygen gradients in uropathogenic Escherichia coli (UPEC) biofilms lead to spatially distinct expression programs for quinol oxidases—components of the terminal electron transport chain. Our studies reveal that the cytochrome bd-expressing subpopulation is critical for biofilm development and matrix production. In addition, we show that quinol oxidases are heterogeneously expressed in planktonic populations and that this respiratory heterogeneity provides a fitness advantage during infection. These studies define the contributions of quinol oxidases to biofilm physiology and suggest the presence of respiratory bet-hedging behavior in UPEC.