ANTIPARASITIC PRODUCTS AND THE GUT MICROBIOME By Dr. Michael W. Fox
Addressing the widespread use of parasiticides and advocating oral or injectable rather than topical products in companion animals on a case-by-case rather than routine, blanket approach, because of concerns over environmental contamination, as reported by Loeb and Scally (1) is a positive initiative. The potential risks to the environment are considerable, however, even with the oral and injectable products. (2).
But oral and injectable parasiticides, including some known to cause seizures and unprovoked aggression in dogs, may cause other health and behavioral issue by adversely impacting the gut microbiome. (3). Conspecific aggression has been correlated with changes in the gut microbiome in rescued dogs. (4). Some dogs are reported to have become aggressive after treatment with parasiticides which was theorized several years ago by veterinarian Dr. Margo Roman (personal communication) to have been caused by oxytocin depletion, and improved after she provided microbiome restorative therapy. More research is called for on this issue considering the widespread use of antiparasitic drugs in companion animals.
Research has found that certain gut microbiota in the intestinal microbiome can affect the production of oxytocin in the intestinal epithelium. Oxytocin regulates social behavior and feeding, and is usually produced in the hypothalamus. However, gut bacteria can stimulate the production of oxytocin through the gut hormone secretin, which is produced in enteroendocrine cells. This process has been called “upregulation” of endogenous oxytocin. The probiotic Limosilactobacillus reuteri (formerly known as Lactobacillus reuteri) has been shown to not only increase circulating oxytocin levels but also oxytocin expression in the brain in rodents, effects which have been linked with metabolism, wound healing, sociability, and behavior. (5, 6, 7).
It is notable that treatment with probiotics to boost oxytocin levels helped reduce obesity, an all-too-common problem in dogs. (8). Prescribing probiotics, therefore, to dogs being given parasiticides on a case-by-case basis is a hypothetical proposition that might prove beneficial in maintaining a healthy gut microbiome and gut-brain axis and in preventing aggression and other behavioural problems. The benefits including so-called postbiotics in fermented foods in the human and canine diets should also be considered. (9, 10).
Microbiome restorative therapy for various behavioural and health issues in human and non-human patients is also being recognized more widely (11,12,13), notably the finding that overweight cats have changes in their gut microbiome like how diet affects the human gut, potentially helping researchers better understand how gut bacteria influence diseases like obesity and type 2 diabetes. (14). Of course, dietary ingredients, additives, and contaminants such as Bisphenol A impact the biodiversity of the gut microbiome. (15).
Also, since glyphosate and other herbicide residues harm the gut-brain-microbiome (16), current widespread agricultural use calls for more restricted applications, and screening especially of corn and soy products. Repeated treatments with ivermectin to prevent heart worm disease can alter the microbiome, facilitating the proliferation of beneficial bacteria. (17). However, the antibacterial properties of ivermectin, although evidence of this is based mainly on in vitro tests, are of concern as prolonged use may lead to gut dysbiosis. In-depth studies are need to be done to determine the effect prolonged use has on gut microbiota and the possibility of developing resistant strains. (18). Our understanding of the gut microbiome and its role in physical and mental health-maintenance is progressing significantly (19), calling for the precautionary principle and more research on the influence of various medications.
References 1. Loeb J, Scally P. Corporate advises against spot-on treatment. Vet Rec 2014; 195: 4. 2. Wells C, Collins C.M.T. A rapid evidence assessment of the potential risk to the environment presented by active ingredients in the UK’s most commonly sold companion animal parasiticides. Environ Sci Pollut Res 2022; 29: 45070–45088 3. Doolin ML, Dearing MD. Differential Effects of Two Common Antiparasitics on Microbiota Resilience. J Infect Dis. 2024: 14;229(3):908-917. 4. Kirchoff NS, Udell MAR, Sharpton TJ. The gut microbiome correlates with conspecific aggression in a small population of rescued dogs (Canis familiaris). PeerJ. 2019 9;7:e61033 5. Cuesta-Marti C, Uhgil F, Muguerza B, et al et al Microbes, oxytocin and stress: Converging players regulating eating behavior. J. Neuroendocrinology 15 February 2023 https://doi.org/10.1111/jne.13243 6. Erdman SE, Poutahidis T. Microbes and Oxytocin: Benefits for Host Physiology and Behavior. Int Rev Neurobiol. 2016; 131: 91-126. 7. Buffington SA, Di Prisco GV, Auchtung TA, et al. Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring. Cell. 2016; 165(7): 1762-1775. 8. Varian BJ, Levkovich T, Poutahidis T, et al. Beneficial dog bacteria up-regulate oxytocin and lower risk of obesity. J Probiotics Health. 2016; 4: 1-9. 9. Liang B, Xing D. The Current and Future Perspectives of Postbiotics. Probiotics Antimicrob Proteins. 2023;15(6):1626-1643. 10. Sabahi S, Homayouni Rad A, Aghebati-Maleki L, et al. Postbiotics as the new frontier in food and pharmaceutical research. Critical Reviews in Food Science and Nutrition, 2022; 63:(26), 8375–8402. 11. Chinna Meyyappan A, Forth E, Wallace CJK, et al. Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review. BMC Psychiatry 2020; 20, 299.https://doi.org/10.1186/s12888-020-02654-5 12. Tan Q, Orsso CE, Deehan EC, Kung JY, et al. Probiotics, prebiotics, symbiotic, and fecal microbiota transplantation in the treatment of behavioral symptoms of autism spectrum disorder: A systematic review. Autism Research 2021; 14:(9), 1820–1836. 13. Collier AJ, Gomez DE, Monteith G, et al Investigating fecal microbial transplant as a novel therapy in dogs with inflammatory bowel disease: A preliminary study. PLoS One. 2022; 17:(10):e0276295. 14. Rowe JC, Winston JA, Parker VJ. et al. Gut microbiota promoting propionic acid production accompanies caloric restriction-induced intentional weight loss in cats. Sci Rep 2024; 14:11901. 15. Lopez-Moreno A, Cerk K, Rodrigo L. et al. Bisphenol A exposure affects specific gut taxa and drives microbiota dynamics in childhood obesity. mSystems 2024; 9:e00957-23.https://doi.org/10.1128/msystems.00957-23