Location: Animal Parasitic Diseases Laboratory
2022 Annual Report
Objectives
Objective 1. Determine the change in the intestinal metabolome and microbiome during parasitic nematode infection and after anti-parasitic clearance.
Sub-objective #1. Characterize parasite-induced molecular mechanisms that modulate intestinal inflammation.
Sub-objective #2. Evaluate the potential impact of Cry5B on the native and parasitized gut microbiome.
Objective 2. Identify pan-nematode secretome products with immune modulating activity that along with nutritional supplements eliminate parasites and enhance enteric health.
Sub-objective #1. Use antibodies from parasite infected pigs and goats to select for immunogenic cloned parasite products that have been computationally identified as vaccine targets.
Sub-objective #2: Test for cloned parasite products that induce innate immune responses at the mucosal surface of explanted intestinal tissues from pigs and goats.
Approach
Objective 1. Determine the change in the intestinal metabolome and microbiome during parasitic nematode infection and after anti-parasitic clearance.
Sub-objective #1. Characterize parasite-induced molecular mechanisms that modulate intestinal inflammation.
Hypothesis #1: Parasitic infections alter the relative abundance of butyrate-producing bacteria in the gut and change the composition and concentration of total short-chain fatty acids (SCFA) as well as anti-inflammatory butyrate, which in turn modulates intestinal inflammation and host immunity.
Sub-objective #2. Evaluate the potential impact of Cry5B on the native and parasitized gut microbiome.
Hypothesis #2: The administration of the Cry5B anthelmintic will have minimal effects on the native microbial community in the gut due to its transient nature and invertebrate gut targets.
Hypothesis #3: Parasite-induced changes in the microbiome will be restored to the native structure and function after treatment with Cry5B that reduces worm burden.
Experimental design: Quantifying changes in the intestinal metabolome and gut microbiome induced by parasitic infection, and characterizing the abilities of anti-parasitic treatments to restore altered gut microbiota, are important in dissecting mechanisms of host pathophysiology and immunity. We will conduct an in-depth comparison of the gut metabolome and microbiome between animals randomly assigned to two conditions (naive and infected) and exposed to Cry5B in an optimally determined delivery system.
Objective 2. Identify pan-nematode secretome products with immune modulating activity that along with nutritional supplements eliminate parasites and enhance enteric health.
Sub-objective #1. Use antibodies from parasite infected pigs and goats to select for immunogenic cloned parasite products that have been computationally identified as vaccine targets.
Hypothesis #1: Immunization of target host species with computationally selected immunogenic cloned parasite products will disrupt parasitism and prevent infections.
Sub-objective #2: Test for cloned parasite products that induce innate immune responses at the mucosal surface of explanted intestinal tissues from pigs and goats.
Hypothesis #2: Selected cloned immunogens that also have innate immune features defined by responses in intestinal explants will enhance vaccine efficacy and disrupt parasitism.
Experimental design:
Powerful new technologies to characterize the transcriptomes from multiple life stages of parasitic nematodes (Heizer et al., 2013) can be used to predict secreted peptides common to the pan-secretome. Combining this bioinformatics approach with antibody detection systems of immune peptides and innate responses of intestinal explanted tissues from pigs and goats will be used to identify vaccine candidates for immunization in the target host species of interest.
Progress Report
Evaluating novel alternatives to dewormers for animal and human parasites. Parasitic Infestation is a serious problem in public health in developing countries and animal production around the globe. Traditional dewormers become less effective due to the rapid spread of anthelmintic resistance. Novel classes of alternative parasitic drugs can have transforming impacts on both human and livestock health. As an FDA approved drug to fight fungal infections, fluconazole has been on the World Health Organization (WHO) List of Essential Medicines. ARS researchers in Beltsville, Maryland, in collaboration with scientists from several domestic and international institutions, screened novel fluconazole analogs for their efficacy against multiple parasite species using in vitro assays and identified at least three candidate compounds with potency against parasitic worms. Animal studies for these compounds are currently under way. Once validated, these candidate compounds will be developed as novel alternatives to dewormers.
Accomplishments
1. Butyrogenic natural products promotes gut health. Butyrate is a short-chain fatty acid produced by microbes and plays a critical role in maintaining gut health. It also helps prevent obesity, stabilize blood sugar levels, and alleviate age-related brain disorders. Approaches that promote a sustained production of butyrate in the intestine are urgently needed. ARS scientists in Beltsville, Maryland, worked with university researchers and evaluated the role of fructo-oligosaccharides (FOS), carbohydrates proven to increase butyrate biosynthesis, in repairing gut barrier function. The research team discovered that FOS is effective in relieving excessive exercise induced stress and maintaining the integrity of gut barriers in animal trials. If translated to humans, these findings suggest that the consumption of FOS-rich butyrogenic foods, such as scallion, onion, garlic, and artichoke, can promote gut health, including alleviating intestinal inflammation and preventing colon cancer.
Review Publications
Cao, W., Liu, F., Li, R.W., Wang, Y. 2022. Transcriptome analysis unravels that triacylglycerol bound docosahexaenoic acid regulates appetite via the mediation of leptin and intestinal epithelial function in animal models. Journal of Nutritional Biochemistry. https://doi.org/10.1016/j.jnutbio.2021.108856.
Pozio, E., Zarlenga, D.S. 2021. Taxonomy of the Trichinella genus. In: Bruschi, Fabrizio, editor. Trichinella and Trichinellosis. London, UK: Elsevier Academic Press. 395-415.
Cao, W., Li, R.W., Chin, Y., Wang, Y., Xue, C., Tang, Q. 2021. Docosahexaenoic acid prevented insulin resistance by modulating gut microbiome and promoting colonic peptide YY expression in diet-induced obesity mice. Food Science and Human Wellness. https://doi.org/10.1016/j.fshw.2021.07.018.
Gao, Y., Liu, F., Li, R.W., Xue, C., Tang, Q. 2022. Microbial composition and co-occurrence patterns in the gut microbial community of healthy and obese mice in response to astaxanthin in its native and lipid emulsion forms. Frontiers in Microbiology. https://doi.org/10.3389/fmicb.2021.671271.
Soto, E., Rus, F., Li, H., Garceau, C., Chicca, J., Elfawal, M., Gazzola, D., Nielsen, M., Urban Jr., J.F., Aroian, R., Ostroff, G. 2021. Yeast particle encapsulation of scaffolded terpene compounds for controlled terpene release. Foods. https://doi.org/10.3390/foods10061207.
Rosa, B.A., Snowden, C., Martin, J., Fisher, K., Kupritz, J., Beshah, E., Supali, T., Gankpala, L., Fisher, P.U., Urban Jr, J.F., Mitreva, M. 2021. Whipworm-associated intestinal microbiome members consistent across both human and mouse hosts. Frontiers in Cellular and Infection Microbiology. https://doi.org/10.3389/fcimb.2021.637570.
