Gut microbial signatures associated with moxidectin treatment efficacy of Haemonchus contortus in infected goats
Graphical abstract
Introduction
The barber's pole worm Haemonchus contortus, a voracious blood sucking parasite of the abomasum of ruminants, represents the primary constraint to profitable sheep and goat production in many regions of the world. The economic cost of the infection is enormous; and it is estimated that the annual cost of roundworms in Australia ranges from $5.80 to $11.09 per ewe, depending on management schemes (https://rune.une.edu.au/web/handle/1959.11/10927). Approximately 80 % of the cost is related to lost production while the remaining 20 % represents the cost of parasite controls. Adult H. contortus worms can consume up to 30 μl of blood per day, rapidly causing severe anemia, affecting feed efficiency and increasing mortality in young animals (Zajac, 2006). Furthermore, the rapid emergence of anthelmintic resistant strains in this parasite species is becoming a serious global concern (Gilleard, 2013). Recent findings suggest that the widespread use of anthelmintics and adaptation to climate changes are shaping genetic diversity in H. contortus (Salle et al., 2019). Evolutionary divergence facilitates the development of a different set of strategies to regulate parasitic infections in small ruminants (Hoste et al., 2010). A direct comparison of eggs per gram of feces (EPG) from sheep and goats grazing together on the same pasture suggests that the mechanisms of resistance in goats are different from those in sheep (Pomroy et al., 1986). Moreover, worldwide production of goats is increasing at a more rapid rate than that of sheep. However, the bulk of our scientific data on host-Haemonchus interactions in small ruminants has been accumulated from ovine studies. As a result, emphasis on specific caprine studies is warranted.
Parasitic infections are known to be associated with profound changes in the structure and function of the host gut microbiome (Afrin et al., 2019; Clark et al., 2018; Li et al., 2016, 2012b; Pan et al., 2019; Wang et al., 2019; Wu et al., 2012). Recently, pathophysiological relevance of the microbiome of different stages of H. contortus under in vitro and in vivo conditions has been recognized (El-Ashram and Suo, 2017; Sinnathamby et al., 2018). Our previous study showed that an experimental H. contortus infection in parasite-naïve Alpine goats reduces bodyweight gain and results in a significant increase in abosamal pH values (Li et al., 2016). The infection causes a profound change in microbial composition at the site of infection, the abomasum. The infection alters the balance of archaea and bacteria and the abundance of ∼ 25 % of the OTUs detected in the abomasal microbiome. The infection-induced alterations in the abomasal microbial community may negatively influence host protein metabolism and immune function. Furthermore, parasitic infections increase the abundance of pathogenic bacteria, such as those in the genus Campylobacter (Li et al., 2012b; Wang et al., 2019), and the family Pasteurellaceae (Li et al., 2016), which may increase the risk of subsequent bacterial and viral disease particularly in parasite susceptible animals (Clark et al., 2018).
While it is generally accepted that parasitic infections are associated with significant alterations in gut microbial composition and function, many other questions remain to be answered. For example, can parasite-induced disruptions in the gut microbiome be restored using anthelmintics? Are there any ecological consequences of a partial drug clearance of parasite worms to the gut microbial community? In this study, we investigated the host-parasite-microbiome interactions using 16S rRNA gene-based approaches and global network algorithms in a goat model. Further, we focused on the potential negative consequences of an ineffective anthelmintic treatment on microbial communities along the gastrointestinal tract in goats infected with H. contortus.
Section snippets
Animal experiment
Sixteen male kid goats [breed: Sire (Boer) x Dam (Kiko x Savanna x Boer)] at an age of 19–28 weeks were purchased locally. All animal care procedures were strictly followed according to a protocol approved by the USDA Beltsville Area Institutional Animal Care Committee (Animal Protocol #12-025). The goats were dewormed with moxidectin at the recommended dose and vaccinated with Clostridium perfringens types C and D and tetanus (CDT vaccine) prior to arrival in Beltsville. The efficacy of
Anthelmintic treatment reduced microbial richness in the proximal colon
Oral administration of a single dose of moxidectin, a milbemycin macrocyclic lactone, to goats experimentally inoculated with H. contortus L3 significantly reduced EPG and worm burden by 83.9 % and 61.8 %, respectively (Fig. 1, P < 0.01) at 16 days after dosing. The treatment led to a marginal improvement in abomasal pH, from 2.97 to 2.54. Unlike in naïve goats, where a primary Haemonchus infection significantly elevated abomasal pH (Li et al., 2016), the goats used in this study had prior
Author contributions
Conceived and designed the experiment: JFU, RVA, RWL
Performed the experiment: FL, YX, AMZ, YH, JFU
Analyzed the data: FL
Wrote the manuscript: FL, RWL
Declaration of Competing Interest
The authors declare that they have no conflict of interest.
Acknowledgments
Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U. S. Department of Agriculture (USDA). The USDA is an equal opportunity provider and employer. YH and RVA were supported by maintenance. The study was supported by National Institutes of Health- National Institute of Allergy and Infectious Diseases (R.V.A., grant number R01 AI056189); Agriculture and Food Research
References (43)
- et al.
Trichuris suis: detection of antibacterial activity in excretory-secretory products from adults
Exp. Parasitol.
(2001) - et al.
Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system
Cell
(2007) - et al.
Goat-nematode interactions: think differently
Trends Parasitol.
(2010) - et al.
Proteobacteria: microbial signature of dysbiosis in gut microbiota
Trends Biotechnol.
(2015) - et al.
Ascaris suum infection was associated with a worm-independent reduction in microbial diversity and altered metabolic potential in the porcine gut microbiome
Int. J. Parasitol.
(2019) Gastrointestinal nematodes of small ruminants: life cycle, anthelmintics, and diagnosis
Vet. Clin. North Am. Food Anim. Pract.
(2006)- et al.
Sequential Changes in the Host Gut Microbiota During Infection With the Intestinal Parasitic Nematode Strongyloides venezuelensis
Front. Cell. Infect. Microbiol.
(2019) - et al.
Deciphering microbial interactions and detecting keystone species with co-occurrence networks
Front. Microbiol.
(2014) - et al.
QIIME allows analysis of high-throughput community sequencing data
Nat. Methods
(2010) - et al.
Molecular diversity of the Planctomycetes in the human gut microbiota in France and Senegal
APMIS
(2013)
Strongyle infection and gut microbiota: profiling of resistant and susceptible horses over a grazing season
Front. Physiol.
Planctomycetes DNA in febrile aplastic patients with leukemia, rash, diarrhea, and micronodular pneumonia
J. Clin. Microbiol.
Exploring the microbial community (microflora) associated with ovine Haemonchus contortus (macroflora) field strains
Sci. Rep.
Unifying the analysis of high-throughput sequencing datasets: characterizing RNA-seq, 16S rRNA gene sequencing and selective growth experiments by compositional data analysis
Microbiome
Haemonchus contortus as a paradigm and model to study anthelmintic drug resistance
Parasitology
Microbiome analysis as a platform R&D tool for parasitic nematode disease management
ISME J.
Chronic trichuris muris infection in C57BL/6 mice causes significant changes in host microbiota and metabolome: effects reversed by pathogen clearance
PLoS One
Parasite-microbiota interactions with the vertebrate gut: synthesis through an ecological Lens
Front. Microbiol.
Butyrate induces profound changes in gene expression related to multiple signal pathways in bovine kidney epithelial cells
BMC Genomics
Metagenome plasticity of the bovine abomasal microbiota in immune animals in response to Ostertagia ostertagi infection
PLoS One
Alterations in the Porcine Colon microbiota induced by the Gastrointestinal Nematode &span class="named-content genus-species" id="named-content-1"&Trichuris suis&/span>
Infect. Immun.
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