Chromosome-length genome assembly of Teladorsagia circumcincta - a globally important helminth parasite in livestock.

BACKGROUND: Gastrointestinal (GIT) helminthiasis is a global problem that affects livestock health, especially in small ruminants. One of the major helminth parasites of sheep and goats, Teladorsagia circumcincta, infects the abomasum and causes production losses, reductions in weight gain, diarrhoea and, in some cases, death in young animals. Control strategies have relied heavily on the use of anthelmintic medication but, unfortunately, T. circumcincta has developed resistance, as have many helminths. Vaccination offers a sustainable and practical solution, but there is no commercially available vaccine to prevent Teladorsagiosis. The discovery of new strategies for controlling T. circumcincta, such as novel vaccine targets and drug candidates, would be greatly accelerated by the availability of better quality, chromosome-length, genome assembly because it would allow the identification of key genetic determinants of the pathophysiology of infection and host-parasite interaction. The available draft genome assembly of T. circumcincta (GCA_002352805.1) is highly fragmented and thus impedes large-scale investigations of population and functional genomics. RESULTS: We have constructed a high-quality reference genome, with chromosome-length scaffolds, by purging alternative haplotypes from the existing draft genome assembly and scaffolding the result using chromosome conformation, capture-based, in situ Hi-C technique. The improved (Hi-C) assembly resulted in six chromosome-length scaffolds with length ranging from 66.6 Mbp to 49.6 Mbp, 35% fewer sequences and reduction in size. Substantial improvements were also achieved in both the values for N50 (57.1 Mbp) and L50 (5 Mbp). A higher and comparable level of genome and proteome completeness was achieved for Hi-C assembly on BUSCO parameters. The Hi-C assembly had a greater synteny and number of orthologs with a closely related nematode, Haemonchus contortus. CONCLUSION: This improved genomic resource is suitable as a foundation for the identification of potential targets for vaccine and drug development.

Quantitative PCR of string-test collected gastric material: A feasible approach to detect Helicobacter pylori and its resistance against clarithromycin and levofloxacin for susceptibility-guided therapy.

BACKGROUND: As the reduced eradication rate of Helicobacter pylori (H. pylori), we introduced string-test and quantitative PCR (qPCR) for susceptibility-guided therapy innovatively. The practicality of the string test was evaluated. METHODS: It was an open-label, non-randomized, parallel, single-center study, in which subjects tested by 13 C- urea breath test (UBT) and string-qPCR were enrolled. Based on the results of string-qPCR, we calculated clarithromycin and levofloxacin resistance rates and gave 13 C-UBT positive patients 14 days susceptibility-guided bismuth quadruple therapy. In the empirical therapy group, we retrospectively analyzed the treatment results of 13 C-UBT positive patients also treated with bismuth quadruple at Shenzhen Luohu People's Hospital from January 2021 to May 2022. The eradication rate was compared between susceptibility-guided therapy and empirical therapy groups. RESULTS: The diagnosis of H. pylori infection using the string-qPCR had an overall concordance rate of 95.9% with the 13 C-UBT results. Based on the results of string-qPCR, the clarithromycin and levofloxacin resistance rates were 26.1% and 31.8%, respectively. The patients who were given 14 days susceptibility-guided bismuth-based quadruple therapy achieved a high H. pylori eradication rate of 91.8%. Retrospective analysis of patient treatment data from January 2021 to May 2022 available in the hospital database revealed an overall success rate of 82.3% for those who received empirical bismuth-based quadruple therapies, which is marginally significantly lower than that of the string-qPCR susceptibility-guided group (p = 0.084). CONCLUSION: The high treatment success rate of 91.8% indicates that the string-qPCR test is a valuable and feasible approach for clinical practice to help improve H. pylori treatment success rate.

Savory, Oregano and Thyme Essential Oil Mixture (HerbELICO®) Counteracts Helicobacter pylori.

Fifty percent of the world's population is infected with Helicobacter pylori, which can trigger many gastrointestinal disorders. H. pylori eradication therapy consists of two to three antimicrobial medicinal products, but they exhibit limited efficacy and may cause adverse side effects. Alternative therapies are urgent. It was assumed that an essential oil mixture, obtained from species from genera Satureja L., Origanum L. and Thymus L. and called the HerbELICO® essential oil mixture, could be useful in H. pylori infection treatment. HerbELICO® was analyzed by GC-MS and assessed in vitro against twenty H. pylori clinical strains isolated from patients of different geographical origins and with different antimicrobial medicinal products resistance profiles, and for its ability to penetrate the artificial mucin barrier. A customer case study included 15 users of HerbELICO®liquid/HerbELICO®solid dietary supplements (capsulated HerbELICO® mixture in liquid/solid form). Carvacrol and thymol were the most dominant compounds (47.44% and 11.62%, respectively), together with p-cymene (13.35%) and γ-terpinene (18.20%). The minimum concentration required to inhibit in vitro H. pylori growth by HerbELICO® was 4-5% (v/v); 10 min exposure to HerbELICO® was enough to kill off the examined H. pylori strains, while HerbELICO® was able to penetrate through mucin. A high eradication rate (up to 90%) and acceptance by consumers was observed.

Contribution of the Immune Response in the Ileum to the Development of Diarrhoea caused by Helminth Infection: Studies with the Sheep Model.

Gastrointestinal helminths are a global health issue, for humans as well as domestic animals. Most studies focus on the tissues that are infected with the parasite, but here we studied the ileum, a tissue that is rarely infected by helminths. We tested whether inflammation in the ileum contributes to the development and severity of diarrhoea, by comparing sheep that are susceptible (n = 4) or resistant (n = 4) to the disease. We analyzed the ileum transcriptome using RNASeq sequencing approach and various bioinformatics tools including FastQC, STAR, featureCounts, DESeq2, DAVID, clusterProfiler, Cytoscape (ClusterONE) and EnrichR. We identified 243 differentially expressed genes (DEGs), of which 118 were up-regulated and 125 were down-regulated DEGs in the diarrhoea-susceptible animals compared to the diarrhoea-resistant animals. The resulting DEGs were functionally enriched for biological processes, pathways and gene set enrichment analysis. The up-regulated DEGs suggested that an inflammatory immune response was coupled with genes involved in 'Th2 immune response' and 'anti-inflammatory response'. The down-regulated DEGs were related to ion transport, muscle contraction and pathways preventing inflammation. We conclude that i) susceptibility to helminth-induced diarrhoea involves an inflammatory response at a non-infectious site; ii) down-regulation of pathways preventing inflammation can contribute to the severity of diarrhoea; and iii) genes involved in anti-inflammatory responses can reduce the inflammation and diarrhoea.

Microbiome data reveal significant differences in the bacterial diversity in freshwater rohu (Labeo rohita) across the supply chain in Dhaka, Bangladesh.

The present study aimed to characterize and compare the skin and gut microbial communities of rohu at various post-harvest stages of consumption using quantitative real-time polymerase chain reaction and 16S rRNA-based amplicon sequencing. Real-time PCR amplification detected higher copy numbers for coliform bacteria-Escherichia coli, Salmonella enterica and Shigella spp. in the marketed fish-compared to fresh and frozen samples. The 16S rRNA data revealed higher alpha diversity measurements in the skin of fish from different retail markets of Dhaka city. Beta ordination revealed distinct clustering of bacterial OTUs for the skin and gut samples from three different groups. At the phylum level, Proteobacteria was most abundant in all groups except the Fusobacteria in the control fish gut. Although Aeromonas was found ubiquitous in all types of samples, diverse bacterial genera were identified in the marketed fish samples. Nonetheless, low species richness was observed for the frozen fish. Most of the differentially abundant bacteria in the skin samples of marketed fish are opportunistic human pathogens enriched at different stages of postharvest handling and processing. Therefore, considering the microbial contamination in the aquatic environment in Bangladesh, post-harvest handling should be performed with proper methods and care to minimize bacterial transmission into fish.

Mutations of Helicobacter pylori RdxA are mainly related to the phylogenetic origin of the strain and not to metronidazole resistance.

OBJECTIVES: Drug resistance of Helicobacter pylori is a major clinical problem worldwide. The objective of the present study was to investigate the prevalence of antibiotic-resistant H. pylori in the city of Shenzhen in China, as well as to identify the genetic mutations specifically associated with drug resistance rather than unrelated phylogenetic signals. METHODS: Antibiotic susceptibility testing was performed on 238 clinical strains successfully isolated from H. pylori-positive dyspeptic patients who underwent gastroscopy at the Department of Gastroenterology in Shenzhen People's Second Hospital. Following WGS of all strains using Illumina technology, mutation and phylogenetic analyses were performed. RESULTS: The resistance rates were 84.9%, 35.3%, 25.2% and 2.1% for metronidazole, clarithromycin, ciprofloxacin and rifampicin, respectively. An A2143G conversion in the 23S rRNA gene was the primary mutation observed in clarithromycin-resistant strains, whilst N87K/I and D91G/N/Y in GyrA were detected in ciprofloxacin-resistant strains. In RdxA, our results demonstrated that only R16H/C and M21A are significant contributors to metronidazole resistance; there were 15 other sites, but these are phylogenetically related and thus unrelated to metronidazole resistance. CONCLUSIONS: There is a high prevalence of metronidazole, clarithromycin and ciprofloxacin resistance and a low prevalence of rifampicin resistance in H. pylori from Shenzhen, China. Omission of phylogenetically related sites will help to improve identification of sites genuinely related to antibiotic resistance in H. pylori and, we believe, other species.

Helicobacter pylori gene silencing in vivo demonstrates urease is essential for chronic infection.

Helicobacter pylori infection causes chronic active gastritis that after many years of infection can develop into peptic ulceration or gastric adenocarcinoma. The bacterium is highly adapted to surviving in the gastric environment and a key adaptation is the virulence factor urease. Although widely postulated, the requirement of urease expression for persistent infection has not been elucidated experimentally as conventional urease knockout mutants are incapable of colonization. To overcome this constraint, conditional H. pylori urease mutants were constructed by adapting the tetracycline inducible expression system that enabled changing the urease phenotype of the bacteria during established infection. Through tight regulation we demonstrate that urease expression is not only required for establishing initial colonization but also for maintaining chronic infection. Furthermore, successful isolation of tet-escape mutants from a late infection time point revealed the strong selective pressure on this gastric pathogen to continuously express urease in order to maintain chronic infection. In addition to mutations in the conditional gene expression system, escape mutants were found to harbor changes in other genes including the alternative RNA polymerase sigma factor, fliA, highlighting the genetic plasticity of H. pylori to adapt to a changing niche. The tet-system described here opens up opportunities to studying genes involved in the chronic stage of H. pylori infection to gain insight into bacterial mechanisms promoting immune escape and life-long infection. Furthermore, this genetic tool also allows for a new avenue of inquiry into understanding the importance of various virulence determinants in a changing biological environment when the bacterium is put under duress.

Corrigendum to "Phenotypic Detection of Metallo-ß-Lactamase in Imipenem-Resistant Pseudomonas aeruginosa".

[This corrects the article DOI: 10.1100/2012/654939.].

Functional characterizations of effector protein BipC, a type III secretion system protein, in Burkholderia pseudomallei pathogenesis.

OBJECTIVES: The bsa locus of Burkholderia pseudomallei encodes several proteins that are components of the type III secretion system (TTSS). BipC was postulated as one of the TTSS-3 effector proteins, but its role in the pathogenesis of B. pseudomallei infection is not well understood. Thus, the aim of this study was to determine its role(s) in the virulence of B. pseudomallei pathogenesis. METHODS: A bipC TTSS-3-deficient strain of B. pseudomallei and complemented strains were generated to assess the role of BipC as a type III translocation apparatus. Human cell lines and a mouse model of melioidosis were used for in vitro and in vivo assays, respectively. RESULTS: A significant 2-fold reduction was demonstrated in the percentage of adherence, invasion, intracellular survival, and phagosomal escape of the bipC mutant. Interestingly, microscopic studies have shown that BipC was capable of delayed B. pseudomallei actin-based motility. The virulence of the mutant strain in a murine model of melioidosis demonstrated that the bipC mutant was less virulent, compared with the wild type. CONCLUSION: The results suggested that BipC possesses virulence determinants that play significant roles in host cell invasion and immune evasion.

The complete methylome of Helicobacter pylori UM032.

BACKGROUND: The genome of the human gastric pathogen Helicobacter pylori encodes a large number of DNA methyltransferases (MTases), some of which are shared among many strains, and others of which are unique to a given strain. The MTases have potential roles in the survival of the bacterium. In this study, we sequenced a Malaysian H. pylori clinical strain, designated UM032, by using a combination of PacBio Single Molecule, Real-Time (SMRT) and Illumina MiSeq next generation sequencing platforms, and used the SMRT data to characterize the set of methylated bases (the methylome). RESULTS: The N4-methylcytosine and N6-methyladenine modifications detected at single-base resolution using SMRT technology revealed 17 methylated sequence motifs corresponding to one Type I and 16 Type II restriction-modification (R-M) systems. Previously unassigned methylation motifs were now assigned to their respective MTases-coding genes. Furthermore, one gene that appears to be inactive in the H. pylori UM032 genome during normal growth was characterized by cloning. CONCLUSION: Consistent with previously-studied H. pylori strains, we show that strain UM032 contains a relatively large number of R-M systems, including some MTase activities with novel specificities. Additional studies are underway to further elucidating the biological significance of the R-M systems in the physiology and pathogenesis of H. pylori.

Determinants of Proteolysis and Cell-Binding for the Shigella flexneri Cytotoxin, SigA.

Shigella flexneri secretes an enterotoxic, SPATE family autotransporter (AT), SigA, which has cytopathic activity towards cultured epithelial cells. Its cytopathic activity is due to its ability to degrade the cytoskeletal protein, α-fodrin. The mechanisms by which AT toxins target cells and tissues differ and the details of how SigA acts are not known. In the current study, the determinants of proteolysis and cell-targeting for SigA were determined. We demonstrate that the SigA passenger or α-domain consists of two functionally distinct domains, designated α1 and α2, which are sufficient to specify proteolytic and cell-binding activities, respectively.

Revealing the associated microflora hosted by the globally significant parasite Trichostrongylus colubriformis.

Trichostrongylus colubriformis is a parasitic helminth that primarily infects small ruminants, causing substantial economic losses in the livestock industry. Exploring the microbiome of this helminth might provide insights into the potential influence of its microbial community on the parasite's survival. We characterised the intestinal microbiome of T. colubriformis that had been collected from the duodenum of sheep, and compared the helminth microbiome with the duodenal microbiome of its host, aiming to identify contributions from the helminth's environment. At the same time, we explored the isolation of fastidious organisms from the harvested helminth. Primary alpha and beta diversity analyses of bacterial species revealed statistically significant differences between the parasite and the host, in terms of species richness and ecological composition. 16S rRNA differential abundance analysis showed that Mycoplasmoides and Stenotrophomonas were significantly present in T. colubriformis but not in the duodenal microbiome of the sheep. Furthermore, two bacteria, Aeromonas caviae and Aeromonas hydrophila, were isolated from T. colubriformis. Examinations of the genome highlight differences in genome size and profiles of antimicrobial resistance genes. Our results suggest that T. colubriformis carries a specific bacterial community that could be supporting the helminth's long-term survival in the host's digestive system.

Association Between Biofilm Formation and Structure and Antibiotic Resistance in H. pylori.

Background: Persistent infections caused by Helicobacter pylori (H. pylori), which are resistant to antibiotic treatment, pose a growing global public health concern. Biofilm formation is known to be associated with persistent infections due to its role in enhancing antimicrobial resistance and the tolerance of many pathogenic bacteria. Objective: This study aims to evaluate the biofilm formation of clinical isolates of H. pylori and its impact on antibiotic eradication. Methods: The thickness, morphology, and structure of biofilms derived from nine H. pylori strains were examined using confocal laser scanning microscopy, scanning electron microscopy, and transmission electron microscopy. Subsequently, the susceptibility of both planktonic and biofilm bacteria was assessed through the determination of minimum inhibitory concentration and minimum biofilm eradication concentration for amoxicillin, clarithromycin, levofloxacin, and tetracycline. Results: The results revealed varying biofilm thicknesses and densities among the strains, characterised by the presence of numerous filaments intertwining and connecting bacterial cells. Additionally, several cases exhibited susceptibility based on MIC measurements but resistance according to MBEC measurements, with MBEC indicating a higher resistance rate. Pearson Correlation analysis demonstrated a positive correlation between biofilm thickness and MBEC results (0 < r < 1), notably significant for amoxicillin (r = 0.801, P = 0.009) and tetracycline (r = 0.696, P = 0.037). Conclusion: Different strains of H. pylori exhibit variations in their capacity to release outer membrane vesicles (OMVs) and form biofilms. Biofilm formation can influence the effectiveness of amoxicillin and tetracycline in eradicating susceptible bacterial strains.

Polymorphism of virulence genes and biofilm associated with in vitro induced resistance to clarithromycin in Helicobacter pylori.

BACKGROUND: Clarithromycin-containing triple therapy is commonly used to treat Helicobacter pylori infections. Clarithromycin resistance is the leading cause of H. pylori treatment failure. Understanding the specific mutations that occur in H. pylori strains that have evolved antibiotic resistance can help create a more effective and individualised antibiotic treatment plan. However, little is understood about the genetic reprogramming linked to clarithromycin exposure and the emergence of antibiotic resistance in H. pylori. Therefore, this study aims to identify compensatory mutations and biofilm formation associated with the development of clarithromycin resistance in H. pylori. Clarithromycin-sensitive H. pylori clinical isolates were induced to develop clarithromycin resistance through in vitro exposure to incrementally increasing concentration of the antibiotic. The genomes of the origin sensitive isolates (S), isogenic breakpoint (B), and resistant isolates (R) were sequenced. Single nucleotide variations (SNVs), and insertions or deletions (InDels) associated with the development of clarithromycin resistance were identified. Growth and biofilm production were also assessed. RESULTS: The S isolates with A2143G mutation in the 23S rRNA gene were successfully induced to be resistant. According to the data, antibiotic exposure may alter the expression of certain genes, including those that code for the Cag4/Cag protein, the vacuolating cytotoxin domain-containing protein, the sel1 repeat family protein, and the rsmh gene, which may increase the risk of developing and enhances virulence in H. pylori. Enhanced biofilm formation was detected among R isolates compared to B and S isolates. Furthermore, high polymorphism was also detected among the genes associated with biofilm production. CONCLUSIONS: Therefore, this study suggests that H. pylori may acquire virulence factors while also developing antibiotic resistance due to clarithromycin exposure.

Draft genome sequences of Helicobacter pylori isolates from Malaysia, cultured from patients with functional dyspepsia and gastric cancer.

Helicobacter pylori is the main bacterial causative agent of gastroduodenal disorders and a risk factor for gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. The draft genomes of 10 closely related H. pylori isolates from the multiracial Malaysian population will provide an insight into the genetic diversity of isolates in Southeast Asia. These isolates were cultured from gastric biopsy samples from patients with functional dyspepsia and gastric cancer. The availability of this genomic information will provide an opportunity for examining the evolution and population structure of H. pylori isolates from Southeast Asia, where the East meets the West.

Phenotypic detection of metallo-ß-lactamase in imipenem-resistant Pseudomonas aeruginosa.

Carbapenems are the primary choice of treatment for severe Pseudomonas aeruginosa infection. However, the emergence of carbapenem resistance due to the production of metallo-ß-lactamases (MBLs) is of global concern. In this study, 90 imipenem- (IPM- or IP-) resistant P. aeruginosa (IRPA) isolates, including 32 previously tested positive and genotyped for MBL genes by PCR, were subjected to double-disk synergy test (DDST), combined disk test (CDT), and imipenem/imipenem-inhibitor (IP/IPI) E-test to evaluate their MBLs detection capability. All three methods were shown to have a sensitivity of 100%. However, DDST was the most specific of the three (96.6%), followed by IP/IPI E-test interpreted based on the single criteria of IP/IPI ≥8 as positive (62.1%), and CDT was the least specific (43.1%). Based on the data from this evaluation, we propose that only IRPA with IP MIC >16 µg/mL and IP/IPI ≥8 by IP/IPI E-test should be taken as positive for MBL activity. With the new dual interpretation criteria, the MBL IP/IPI E-test was shown to achieve 100% sensitivity as well as specificity for the IRPA in this study. Therefore, the IP/IPI E-test is a viable alternative phenotypic assay to detect MBL production in IRPA in our population in circumstances where PCR detection is not a feasible option.

Investigating the development of diarrhoea through gene expression analysis in sheep genetically resistant to gastrointestinal helminth infection.

Gastrointestinal helminths infect livestock causing health problems including severe diarrhoea. To explore the underlying biological mechanisms relating to development and control of diarrhoea, we compared 4 sheep that were susceptible to development of diarrhoea with 4 sheep that were diarrhoea-resistant. Transcriptomes in the tissues where the parasites were located were analyzed using RNASeq. By considering low-diarrhoea sheep as control, we identified 114 genes that were down-regulated and 552 genes that were up-regulated genes in the high-diarrhoea phenotype. Functional analysis of DEGs and PPI sub-network analysis showed that down-regulated genes in the high-diarrhoea phenotype were linked to biological processes and pathways that include suppression of 'antigen processing and presentation', 'immune response', and a list of biological functional terms related to 'suppression in immune tolerance'. On the other hand, up-regulated genes in the high-diarrhoea phenotype probably contribute to repair processes associated with tissue damage, including 'extracellular matrix organization', 'collagen fibril organization', 'tissue morphogenesis', 'circulatory system development', 'morphogenesis of an epithelium', and 'focal adhesion'. The genes with important roles in the responses to helminth infection could be targeted in breeding programs to prevent diarrhoea.

Changes in the rodent gut microbiome following chronic restraint stress and low-intensity rTMS.

Gut microbiome composition is associated with mood-relating behaviours, including those reflecting depression-like phenotypes. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, is an effective treatment for depression, but its effects on the gut microbiome remain largely unknown. This study assessed microbial changes from rat faecal samples longitudinally following chronic restraint stress (CRS) and 10 Hz low-intensity rTMS treatment. CRS increased abundance within the Proteobacteria (Deltaproteobacteria, Desulfovibrionales) and Firmicutes (Anaerostipes, Frinsingococcus), with decreases in Firmicutes family (Acidaminococcaceae) and genera (Roseburia, Phascolarctobacterium and Fusicatenibacter) persisting for up to 4 weeks post CRS. The decrease in Firmicutes was not observed in the handling control and LI-rTMS groups, suggesting that handling alone may have sustained changes in gut microbiome associated with CRS. Nonetheless, LI-rTMS was specifically associated with an increase in Roseburia genus that developed 2 weeks after treatment, and the abundance of both Roseburia and Fusicatenibacter genera was significantly correlated with rTMS behavioural and MRI outcomes. In addition, LI-rTMS treated rats had a reduction in apoptosis pathways and several indicators of reduced inflammatory processes. These findings provide evidence that the brain can influence the gut microbiome in a "top-down" manner, presumably via stimulation of descending pathways, and/or indirectly via behavioural modification.

Bacterial communities in the gastrointestinal tract segments of helminth-resistant and helminth-susceptible sheep.

BACKGROUND: Helminth parasitism is a world-wide problem in livestock industries, with major impacts on health, welfare and productivity. The role of the gut microbiota in host-helminth interactions in ruminants has been extensively examined and the present study added to this body of knowledge by assessing the effects of resistance and susceptibility to helminth infection in the gastro-intestinal tract (GIT). Australian Sheep Breeding Values (ASBVs) for faecal egg count (FEC) were used to select the 10 highly helminth-susceptible (High-FEC) and 10 highly helminth-resistant (Low-FEC) sheep. FEC status was confirmed during the experiment. Using samples from the faeces and the lumen of the rumen, abomasum, duodenum, jejunum, ileum, caecum, and colon, DNA was extracted and used for 16 rRNA gene amplicon sequencing. RESULTS: The most frequent genera identified along the GIT were Eubacterium, Oscillibacter, and Ruminococcus. Intersectoral-specialization zones were identified along the GIT, with the duodenum displaying major differences between the High-FEC and Low-FEC animals in values for alpha and beta diversity. After taking all samples into account and adjusting for GIT segment, the High-FEC and Low-FEC sheep differed significantly for four genera Butyrivibrio, Mycoplasma, Lachnoclostridium and Succiniclasticum. In the duodenum, the abundances of Aminipila, Lachnoclostridium and Mogibacterium differed significantly between the High-FEC and Low-FEC sheep. In the ileum, on the other hand, the genus Mycoplasma was significantly depleted in the Low-FEC group. CONCLUSIONS: The gastro-intestinal microbial profile varies widely between helminth-resistant and helminth-susceptible sheep. Each GIT section appears to support a particular bacterial composition leading to inter-sectoral differences among the various microbial communities. The microbial populations were most rich and diverse in the duodenum of helminth-resistant sheep, comprising bacterial genera that generally ferment carbohydrates. This observation suggests that helminth-resistant sheep can reorganize the duodenal microbiome taxa which may restrict the development of parasites.

Changes in the Gut Microbiome and Predicted Functional Metabolic Effects in an Australian Parkinson's Disease Cohort.

Background: There has been increasing recognition of the importance of the gut microbiome in Parkinson's disease (PD), but the influence of geographic location has received little attention. The present study characterized the gut microbiota and associated changes in host metabolic pathways in an Australian cohort of people with PD (PwP). Methods: The study involved recruitment and assessment of 87 PwP from multiple Movement Disorders Clinics in Australia and 47 healthy controls. Illumina sequencing of the V3 and V4 regions of the 16S rRNA gene was used to distinguish inter-cohort differences in gut microbiota; KEGG analysis was subsequently performed to predict functional changes in host metabolic pathways. Results: The current findings identified significant differences in relative abundance and diversity of microbial operational taxonomic units (OTUs), and specific bacterial taxa between PwP and control groups. Alpha diversity was significantly reduced in PwP when compared to controls. Differences were found in two phyla (Synergistetes and Proteobacteria; both increased in PwP), and five genera (Colidextribacter, Intestinibacter, Kineothrix, Agathobaculum, and Roseburia; all decreased in PwP). Within the PD cohort, there was no association identified between microbial composition and gender, constipation or use of gastrointestinal medication. Furthermore, KEGG analysis identified 15 upregulated and 11 downregulated metabolic pathways which were predicted to be significantly altered in PwP. Conclusion: This study provides the first comprehensive characterization of the gut microbiome and predicted functional metabolic effects in a southern hemisphere PD population, further exploring the possible mechanisms whereby the gut microbiota may exert their influence on this disease, and providing evidence for the incorporation of such data in future individualized therapeutic strategies.