scholarly journals Omadacycline Gut Microbiome Exposure Does Not InduceClostridium difficileProliferation or Toxin Production in a Model That Simulates the Proximal, Medial, and Distal Human Colon

2018 ◽  
Vol 63 (2) ◽  
pp. e01581-18 ◽  
Author(s):  
Ines B. Moura ◽  
Anthony M. Buckley ◽  
Duncan Ewin ◽  
Sharie Shearman ◽  
Emma Clark ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Human Colon ◽  
Toxin Production ◽  
Parallel Study ◽  
Broad Spectrum Antibiotic ◽  
Once Daily ◽  
Content Type ◽  
Pcr Ribotype 027

ABSTRACTA clinically reflective model of the human colon was used to investigate the effects of the broad-spectrum antibiotic omadacycline on the gut microbiome and the subsequent potential to induce simulatedClostridium difficileinfection (CDI). Triple-stage chemostat gut models were inoculated with pooled human fecal slurry from healthy volunteers (age, ≥60 years). Models were challenged twice with 107CFUC. difficilespores (PCR ribotype 027). Omadacycline effects were assessed in a single gut model. Observations were confirmed in a parallel study with omadacycline and moxifloxacin. Antibiotic instillation was performed once daily for 7 days. The models were observed for 3 weeks postantibiotic challenge. Gut microbiota populations andC. difficiletotal viable and spore counts were enumerated daily by culture. Cytotoxin titers and antibiotic concentrations were also measured. Gut microbiota populations were stable before antibiotic challenge. Moxifloxacin instillation caused an ∼4 log10CFU/ml decline in enterococci andBacteroides fragilisgroup populations and an ∼3 log10CFU/ml decline in bifidobacteria and lactobacilli, followed by simulated CDI (vegetative cell proliferation and detectable toxin). In both models, omadacycline instillation decreased populations of bifidobacteria (∼8 log10CFU/ml),B. fragilisgroup populations (7 to 8 log10CFU/ml), lactobacilli (2 to 6 log10CFU/ml), and enterococci (4 to 6 log10CFU/ml). Despite these microbial shifts, there was no evidence ofC. difficilebacteria germination or toxin production. In contrast to moxifloxacin, omadacycline exposure did not facilitate simulated CDI, suggesting this antibiotic may have a low propensity to induce CDI in the clinical setting.

scholarly journals An Attenuated Salmonella enterica Serovar Typhimurium Strain and Galacto-Oligosaccharides Accelerate Clearance of Salmonella Infections in Poultry through Modifications to the Gut Microbiome

2017 ◽  
Vol 84 (5) ◽  
Author(s):  
M. Andrea Azcarate-Peril ◽  
Natasha Butz ◽  
Maria Belen Cadenas ◽  
Matthew Koci ◽  
Anne Ballou ◽  
...  
Keyword(s):  
United States ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Salmonella Enterica ◽  
The United States ◽  
Wild Type ◽  
Content Type ◽  
Salmonella Infections ◽  
Serovar Typhimurium ◽  
The Impact

ABSTRACT Salmonella is estimated to cause one million foodborne illnesses in the United States every year. Salmonella -contaminated poultry products are one of the major sources of salmonellosis. Given the critical role of the gut microbiota in Salmonella transmission, a manipulation of the chicken intestinal microenvironment could prevent animal colonization by the pathogen. In Salmonella , the global regulator gene fnr ( f umarate n itrate r eduction) regulates anaerobic metabolism and is essential for adapting to the gut environment. This study tested the hypothesis that an attenuated Fnr mutant of Salmonella enterica serovar Typhimurium (attST) or prebiotic galacto-oligosaccharides (GOS) could improve resistance to wild-type Salmonella via modifications to the structure of the chicken gut microbiome. Intestinal samples from a total of 273 animals were collected weekly for 9 weeks to evaluate the impact of attST or prebiotic supplementation on microbial species of the cecum, duodenum, jejunum, and ileum. We next analyzed changes to the gut microbiome induced by challenging the animals with a wild-type Salmonella serovar 4,[5],12:r:− (Nal r ) strain and determined the clearance rate of the virulent strain in the treated and control groups. Both GOS and the attenuated Salmonella strain modified the gut microbiome but elicited alterations of different taxonomic groups. The attST produced significant increases of Alistipes and undefined Lactobacillus , while GOS increased Christensenellaceae and Lactobacillus reuteri . The microbiome structural changes induced by both treatments resulted in a faster clearance after a Salmonella challenge. IMPORTANCE With an average annual incidence of 13.1 cases/100,000 individuals, salmonellosis has been deemed a nationally notifiable condition in the United States by the Centers for Disease Control and Prevention (CDC). Earlier studies demonstrated that Salmonella is transmitted by a subset of animals (supershedders). The supershedder phenotype can be induced by antibiotics, ascertaining an essential role for the gut microbiota in Salmonella transmission. Consequently, modulation of the gut microbiota and modification of the intestinal microenvironment could assist in preventing animal colonization by the pathogen. Our study demonstrated that a manipulation of the chicken gut microbiota by the administration of an attenuated Salmonella strain or prebiotic galacto-oligosaccharides (GOS) can promote resistance to Salmonella colonization via increases of beneficial microorganisms that translate into a less hospitable gut microenvironment.

scholarly journals Effects of Exposure of Clostridium difficile PCR Ribotypes 027 and 001 to Fluoroquinolones in a Human Gut Model

2008 ◽  
Vol 53 (2) ◽  
pp. 412-420 ◽  
Author(s):  
Katie Saxton ◽  
Simon D. Baines ◽  
Jane Freeman ◽  
Rachael O'Connor ◽  
Mark H. Wilcox
Keyword(s):  
Clostridium Difficile ◽  
Gut Microbiota ◽  
Spore Germination ◽  
Toxin Production ◽  
Human Gut ◽  
Ribotype 027 ◽  
Resistant Mutants ◽  
High Level ◽  
Pcr Ribotype 027

ABSTRACT The incidence of Clostridium difficile infection is increasing, with reports implicating fluoroquinolone use. A three-stage chemostat gut model was used to study the effects of three fluoroquinolones (ciprofloxacin, levofloxacin, and moxifloxacin) on the gut microbiota and two epidemic C. difficile strains, strains of PCR ribotypes 027 and 001, in separate experiments. C. difficile total viable counts, spore counts, and cytotoxin titers were determined. The emergence of C. difficile isolates with reduced antibiotic susceptibility was monitored with fluoroquinolone-containing medium, and molecular analysis of the quinolone resistance-determining region was performed. C. difficile spores were quiescent in the absence of fluoroquinolones. Instillation of each fluoroquinolone led to C. difficile spore germination and high-level cytotoxin production. High-level toxin production occurred after detectable spore germination in all experiments except those with C. difficile PCR ribotype 027 and moxifloxacin, in which marked cytotoxin production preceded detectable germination, which coincided with isolate recovery on fluoroquinolone-containing medium. Three C. difficile PCR ribotype 027 isolates and one C. difficile PCR ribotype 001 isolate from fluoroquinolone-containing medium exhibited elevated MICs (80 to ≥180 mg/liter) and possessed mutations in gyrA or gyrB. These in vitro results suggest that all fluoroquinolones have the propensity to induce C. difficile infection, regardless of their antianaerobe activities. Resistant mutants were seen only following moxifloxacin exposure.

scholarly journals Oral Administration ofPorphyromonas gingivalisAlters the Gut Microbiome and Serum Metabolome

mSphere ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Tamotsu Kato ◽  
Kyoko Yamazaki ◽  
Mayuka Nakajima ◽  
Yasuhiro Date ◽  
Jun Kikuchi ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Periodontal Disease ◽  
Oral Administration ◽  
Gut Microbiome ◽  
Metabolic Diseases ◽  
Microbiota Composition ◽  
Content Type ◽  
Increased Risk ◽  
Metabolite Profiles ◽  
Gut Microbiota Composition

ABSTRACTPeriodontal disease induced by periodontopathic bacteria likePorphyromonas gingivalisis demonstrated to increase the risk of metabolic, inflammatory, and autoimmune disorders. Although precise mechanisms for this connection have not been elucidated, we have proposed mechanisms by which orally administered periodontopathic bacteria might induce changes in gut microbiota composition, barrier function, and immune system, resulting in an increased risk of diseases characterized by low-grade systemic inflammation. Accumulating evidence suggests a profound effect of altered gut metabolite profiles on overall host health. Therefore, it is possible thatP. gingivaliscan affect these metabolites. To test this, C57BL/6 mice were administered withP. gingivalisW83 orally twice a week for 5 weeks and compared with sham-inoculated mice. The gut microbial communities were analyzed by pyrosequencing the 16S rRNA genes. Inferred metagenomic analysis was used to determine the relative abundance of KEGG pathways encoded in the gut microbiota. Serum metabolites were analyzed using nuclear magnetic resonance (NMR)-based metabolomics coupled with multivariate statistical analyses. Oral administration ofP. gingivalisinduced a change in gut microbiota composition. The distributions of metabolic pathways differed between the two groups, including those related to amino acid metabolism and, in particular, the genes for phenylalanine, tyrosine, and tryptophan biosynthesis. Also, alanine, glutamine, histidine, tyrosine, and phenylalanine were significantly increased in the serum ofP. gingivalis-administered mice. In addition to altering immune modulation and gut barrier function, oral administration ofP. gingivalisaffects the host’s metabolic profile. This supports our hypothesis regarding a gut-mediated systemic pathology resulting from periodontal disease.IMPORTANCEIncreasing evidence suggest that alterations of the gut microbiome underlie metabolic disease pathology by modulating gut metabolite profiles. We have shown that orally administeredPorphyromonas gingivalis, a representative periodontopathic bacterium, alters the gut microbiome; that may be a novel mechanism by which periodontitis increases the risk of various diseases. Given the association between periodontal disease and metabolic diseases, it is possible thatP. gingivaliscan affect the metabolites. Metabolite profiling analysis demonstrated that several amino acids related to a risk of developing diabetes and obesity were elevated inP. gingivalis-administered mice. Our results revealed that the increased risk of various diseases byP. gingivalismight be mediated at least in part by alteration of metabolic profiles. The findings should add new insights into potential links between periodontal disease and systemic disease for investigators in periodontal disease and also for investigators in the field of other diseases, such as metabolic diseases.

scholarly journals Multiple-Ascending-Dose Phase 1 Clinical Study of the Safety, Tolerability, and Pharmacokinetics of CRS3123, a Narrow-Spectrum Agent with Minimal Disruption of Normal Gut Microbiota

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
Barbara K. Lomeli ◽  
Hal Galbraith ◽  
Jared Schettler ◽  
George A. Saviolakis ◽  
Wael El-Amin ◽  
...  
Keyword(s):  
Adverse Events ◽  
Gut Microbiota ◽  
Phase 1 ◽  
Toxin Production ◽  
Trna Synthetase ◽  
Serious Adverse Events ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Clinically Significant ◽  
Microbiome Data

ABSTRACT CRS3123 is a novel small molecule that potently inhibits methionyl-tRNA synthetase of Clostridioides difficile, inhibiting C. difficile toxin production and spore formation. CRS3123 has been evaluated in a multiple-ascending-dose placebo-controlled phase 1 trial. Thirty healthy subjects, ages 18 to 45 years, were randomized into three cohorts of 10 subjects each, receiving either 200, 400, or 600 mg of CRS3123 (8 subjects per cohort) or placebo (2 subjects per cohort) by oral administration twice daily for 10 days. CRS3123 was generally safe and well tolerated, with no serious adverse events (SAEs) or severe treatment-emergent adverse events (TEAEs) reported. All subjects completed their assigned treatment and follow-up visits, and there were no trends in systemic, vital sign, or laboratory TEAEs. There were no QTcF interval changes or any clinically significant changes in other electrocardiogram (ECG) intervals or morphology. CRS3123 showed limited but detectable systemic uptake; although absorption increased with increasing dose, the increase was less than dose proportional. Importantly, the bulk of the oral dose was not absorbed, and fecal concentrations were substantially above the MIC90 value of 1 μg/ml at all dosages tested. Subjects receiving either of the two lower doses of CRS3123 exhibited minimal disruption of normal gut microbiota after 10 days of twice-daily dosing. CRS3123 was inactive against important commensal anaerobes, including Bacteroides, bifidobacteria, and commensal clostridia. Microbiome data showed favorable differentiation compared to other CDI therapeutics. These results support further development of CRS3123 as an oral agent for the treatment of CDI. (This study has been registered at Clinicaltrials.gov under identifier NCT02106338.)

scholarly journals An In Vitro Protocol to Study the Modulatory Effects of a Food or Biocompound on Human Gut Microbiome and Metabolome

Foods ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3020
Author(s):  
Carles Rosés ◽  
Juan Antonio Nieto ◽  
Blanca Viadel ◽  
Elisa Gallego ◽  
Ana Romo-Hualde ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Treatment Period ◽  
Gut Microbiome ◽  
Human Colon ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
16S Rrna Gene Analysis ◽  
Physiological Conditions ◽  
Metabolic Functions

The gut microbiota plays a key role in gastrointestinal immune and metabolic functions and is influenced by dietary composition. An in vitro protocol simulating the physiological conditions of the digestive system helps to study the effects of foods/biocompounds on gut microbiome and metabolome. The Dynamic-Colonic Gastrointestinal Digester consists of five interconnected compartments, double jacket vessels that simulate the physiological conditions of the stomach, the small intestine and the three colonic sections, which are the ascending colon, transverse colon and descending colon. Human faeces are required to reproduce the conditions and culture medium of the human colon, allowing the growth of the intestinal microbiota. After a stabilization period of 12 days, a food/biocompound can be introduced to study its modulatory effects during the next 14 days (treatment period). At the end of the stabilization and treatment period, samples taken from the colon compartments are analysed. The 16S rRNA gene analysis reveals the microbiota composition. The untargeted metabolomics analysis gives more than 10,000 features (metabolites/compounds). The present protocol allows in vitro testing of the modulatory effects of foods or biocompounds on gut microbiota composition and metabolic activity.

scholarly journals Sleep and the gut microbiome: antibiotic-induced depletion of the gut microbiota reduces nocturnal sleep in mice

2017 ◽  
Author(s):  
Jonathan Lendrum ◽  
Bradley Seebach ◽  
Barrett Klein ◽  
Sumei Liu
Keyword(s):  
Cell Wall ◽  
Locomotor Activity ◽  
Gut Microbiota ◽  
Broad Spectrum ◽  
Gut Microbiome ◽  
Bacterial Cell ◽  
Broad Spectrum Antibiotic ◽  
Nocturnal Sleep ◽  
Sleep Behavior ◽  
Diurnal Sleep

AbstractSeveral bacterial cell wall components such as peptidoglycan and muramyl peptide are potent inducers of mammalian slow-wave sleep when exogenously administered to freely behaving animals. It has been proposed that the native gut microflora may serve as a quasi-endogenous pool of somnogenic bacterial cell wall products given their quantity and close proximity to the intestinal portal. This proposal suggests that deliberate manipulation of the host's intestinal flora may elicit changes in host sleep behavior. To test this possibility, we evaluated 24 h of sleep-wake behavior after depleting the gut microbiota with a 14 d broad-spectrum antibiotic regimen containing high doses of ampicillin, metronidazole, neomycin, and vancomycin. High-throughput sequencing of the bacterial 16S rDNA gene was used to confirm depletion of fecal bacteria and sleep-wake vigilance states were determined using videosomnography techniques based on previously established behavioral criteria shown to highly correlate with standard polysomnography-based methods. Additionally, considering that germ-free and antibiotic-treated mice have been earlier shown to display increased locomotor activity, and since locomotor activity has been used as a reliable proxy of sleep, we suspected that the elevated locomotor activity previously reported in these animals may reflect an unreported reduction in sleep behavior. To examine this potential relationship, we also quantified locomotor activity on a representative subsample of the same 24 h of video recordings using the automated video-tracking software ANY-maze. We found that antibiotic-induced depletion of the gut microbiota reduced nocturnal sleep, but not diurnal sleep. Likewise, antibiotic-treated mice showed increased nocturnal locomotor activity, but not diurnal locomotor activity. Taken together, these results support a link between the gut microbiome and nocturnal sleep and locomotor physiology in adult mice. Additionally, our findings indicate that antibiotics may be insomnogenic via their ability to diminish gut-derived bacterial somnogens. Given that antibiotics are among the most commonly prescribed drugs in human medicine, these findings have important implications for clinical practice with respect to prolonged antibiotic therapy, insomnia, and other idiopathic sleep-wake and circadian-rhythm disorders affecting an estimated 50-70 million people in the United States alone.Highlights-14 d broad-spectrum antibiotic treatment effectively depletes the gut microbiota.-Gut microbiota depletion reduces nocturnal sleep, but not diurnal sleep.-Gut microbiota depletion increases nocturnal locomotion, but not diurnal locomotion.-Antibiotics may be insomnogenic: implications for idiopathic sleep disorders.

scholarly journals The Impact of Anthelmintic Treatment on Human Gut Microbiota Based on Cross-Sectional and Pre- and Postdeworming Comparisons in Western Kenya

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Alice V. Easton ◽  
Mariam Quiñones ◽  
Ivan Vujkovic-Cvijin ◽  
Rita G. Oliveira ◽  
Stella Kepha ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Intestinal Parasites ◽  
Fold Change ◽  
Rrna Gene ◽  
Human Gut ◽  
Microbial Composition ◽  
Content Type ◽  
Average Fold Change ◽  
The Impact

ABSTRACT Murine studies suggest that the presence of some species of intestinal helminths is associated with changes in host microbiota composition and diversity. However, studies in humans have produced varied conclusions, and the impact appears to vary widely depending on the helminth species present. To demonstrate how molecular approaches to the human gut microbiome can provide insights into the complex interplay among disparate organisms, DNA was extracted from cryopreserved stools collected from residents of 5 rural Kenyan villages prior to and 3 weeks and 3 months following albendazole (ALB) therapy. Samples were analyzed by quantitative PCR (qPCR) for the presence of 8 species of intestinal parasites and by MiSeq 16S rRNA gene sequencing. Based on pretreatment results, the presence of neither Ascaris lumbricoides nor Necator americanus infection significantly altered the overall diversity of the microbiota in comparison with age-matched controls. Following ALB therapy and clearance of soil-transmitted helminths (STH), there were significant increases in the proportion of the microbiota made up by Clostridiales (P = 0.0002; average fold change, 0.57) and reductions in the proportion made up by Enterobacteriales (P = 0.0004; average fold change, −0.58). There was a significant posttreatment decrease in Chao1 richness, even among individuals who were uninfected pretreatment, suggesting that antimicrobial effects must be considered in any posttreatment setting. Nevertheless, the helminth-associated changes in Clostridiales and Enterobacteriales suggest that clearance of STH, and of N. americanus in particular, alters the gut microbiota. IMPORTANCE The gut microbiome is an important factor in human health. It is affected by what we eat, what medicines we take, and what infections we acquire. In turn, it affects the way we absorb nutrients and whether we have excessive intestinal inflammation. Intestinal worms may have an important impact on the composition of the gut microbiome. Without a complete understanding of the impact of mass deworming programs on the microbiome, it is impossible to accurately calculate the cost-effectiveness of such public health interventions and to guard against any possible deleterious side effects. Our research examines this question in a “real-world” setting, using a longitudinal cohort, in which individuals with and without worm infections are treated with deworming medication and followed up at both three weeks and three months posttreatment. We quantify the impact of roundworms and hookworms on gut microbial composition, suggesting that the impact is small, but that treatment of hookworm infection results in significant changes. This work points to the need for follow-up studies to further examine the impact of hookworm on the gut microbiota and determine the health consequences of the observed changes.

scholarly journals The Core Gut Microbiome of the American Cockroach, Periplaneta americana, Is Stable and Resilient to Dietary Shifts

2016 ◽  
Vol 82 (22) ◽  
pp. 6603-6610 ◽  
Author(s):  
Kara A. Tinker ◽  
Elizabeth A. Ottesen
Keyword(s):  
Microbial Community ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Periplaneta Americana ◽  
Community Change ◽  
American Cockroach ◽  
Core Microbiome ◽  
Content Type ◽  
Stable Core ◽  
Dietary Shifts

ABSTRACTThe omnivorous cockroachPeriplaneta americanahosts a diverse hindgut microbiota encompassing hundreds of microbial species. In this study, we used 16S rRNA gene sequencing to examine the effect of diet on the composition of theP. americanahindgut microbial community. Results show that the hindgut microbiota ofP. americanaexhibit a highly stable core microbial community with low variance in compositions between individuals and minimal community change in response to dietary shifts. This core hindgut microbiome is shared between laboratory-hosted and wild-caught individuals, although wild-caught specimens exhibited a higher diversity of low-abundance microbes that were lost following extended cultivation under laboratory conditions. This taxonomic stability strongly contrasts with observations of the gut microbiota of mammals, which have been shown to be highly responsive to dietary change. A comparison ofP. americanahindgut samples with human fecal samples indicated that the cockroach hindgut community exhibited higher alpha diversity but a substantially lower beta diversity than the human gut microbiome. This suggests that cockroaches have evolved unique mechanisms for establishing and maintaining a diverse and stable core microbiome.IMPORTANCEThe gut microbiome plays an important role in the overall health of its host. A healthy gut microbiota typically assists with defense against pathogens and the digestion and absorption of nutrients from food, while dysbiosis of the gut microbiota has been associated with reduced health. In this study, we examined the composition and stability of the gut microbiota from the omnivorous cockroachPeriplaneta americana.We found thatP. americanahosts a diverse core gut microbiome that remains stable after drastic long-term changes in diet. While other insects, notably ant and bee species, have evolved mechanisms for maintaining a stable association with specific gut microbiota, these insects typically host low-diversity gut microbiomes and consume specialized diets. In contrast,P. americanahosts a gut microbiota that is highly species rich and consumes a diverse solid diet, suggesting that cockroaches have evolved unique mechanisms for developing and maintaining a stable gut microbiota.

scholarly journals Precise Manipulation of the Clostridium difficile Chromosome Reveals a Lack of Association between thetcdCGenotype and Toxin Production

2012 ◽  
Vol 78 (13) ◽  
pp. 4683-4690 ◽  
Author(s):  
Stephen T. Cartman ◽  
Michelle L. Kelly ◽  
Daniela Heeg ◽  
John T. Heap ◽  
Nigel P. Minton
Keyword(s):  
Clostridium Difficile ◽  
Diarrheal Disease ◽  
Genetic Manipulation ◽  
Toxin Production ◽  
Negative Regulator ◽  
Toxin B ◽  
Content Type ◽  
Ribotype 027 ◽  
High Level ◽  
Pcr Ribotype 027

ABSTRACTClostridium difficilecauses a potentially fatal diarrheal disease through the production of its principal virulence factors, toxin A and toxin B. ThetcdCgene is thought to encode a negative regulator of toxin production. Therefore, increased toxin production, and hence increased virulence, is often inferred in strains with an aberranttcdCgenotype. This report describes the first allele exchange system for precise genetic manipulation ofC. difficile, using thecodAgene ofEscherichia colias a heterologous counterselection marker. It was used to systematically restore the Δ117 frameshift mutation and the 18-nucleotide deletion that occur naturally in thetcdCgene ofC. difficileR20291 (PCR ribotype 027). In addition, the naturally intacttcdCgene ofC. difficile630 (PCR ribotype 012) was deleted and then subsequently restored with a silent nucleotide substitution, or “watermark,” so the resulting strain was distinguishable from the wild type. Intriguingly, there was no association between thetcdCgenotype and toxin production in eitherC. difficileR20291 orC. difficile630. Therefore, an aberranttcdCgenotype does not provide a broadly applicable rationale for the perceived notion that PCR ribotype 027 strains are “high-level” toxin producers. This may well explain why several studies have reported that an aberranttcdCgene does not predict increased toxin production or, indeed, increased virulence.

scholarly journals Heritable Gut Microbiome Associated with Salmonella enterica Serovar Pullorum Infection in Chickens

mSystems ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jinmei Ding ◽  
Hao Zhou ◽  
Lingxiao Luo ◽  
Lu Xiao ◽  
Kaixuan Yang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Microbial Diversity ◽  
Gut Microbiome ◽  
Genetic Variants ◽  
Salmonella Enterica ◽  
Genome Wide Association Study ◽  
Genetic Mutations ◽  
Content Type ◽  
Gut Microbes ◽  
Host Genetic

ABSTRACT Pullorum disease is one of the most common diarrhea-related diseases caused by Salmonella enterica subspecies enterica serovar Gallinarum biovar Pullorum (S. Pullorum); it negatively affects the poultry industry. However, limited studies have explored the association between the gut microbiota and S. Pullorum infection in chickens. In the present study, we performed a microbiome comparison and a microbiome genome-wide association study (mGWAS) to investigate the association among the host genetics, the gut microbiota, and pullorum disease in chickens. We found that S. Pullorum infection in chickens could alter the abundance of 39 bacterial genera (P < 0.05). The altered structure and composition of the gut microbiota were also detected in the offspring. mGWAS results revealed host genetic variants to be prominently associated with gut microbial diversity and individual microbes. The pathogens Pelomonas and Brevundimonas, which had a high abundance in positive parent chickens and their offspring, were significantly associated with several genetic mutations in immunity-related genes, such as TGIF1, TTLL12, and CCR7. This finding explained why Pelomonas and Brevundimonas were heritable in S. Pullorum-infected chickens. The heritable gut microbes and identified genetic variants could provide references for the selection of resistant chickens and the elimination of pullorum disease. IMPORTANCE The present study investigated the association among the host genome, the gut microbiome, and S. Pullorum infection in chickens. The results suggested that the gut microbial structure is altered in S. Pullorum-infected chickens. The diversity and abundance of the gut microbiota remarkably differed between the offspring coming from S. Pullorum-positive and S. Pullorum-negative chickens. Heritable gut microbiota were detected in the offspring. Moreover, host genetic variants were associated with microbial diversity and individual gut microbes. The pathogens Pelomonas and Brevundimonas, which exhibited a high heritability in S. Pullorum-positive parents and their offspring, were associated with several genetic mutations in immunity-related genes.

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