Ascaris suum Nutrient Uptake and Metabolic Release, and Modulation of Host Intestinal Nutrient Transport by Excretory-Secretory and Cuticle Antigens In Vitro

Abstract

Ascaris suum, the most important pig parasite, also infects humans as a zoonotic pathogen. Malabsorption upon infection probably results from impaired nutrient transport, presumably mediated by the parasite’s excretory-secretory (ES) or cuticle somatic (CSO) antigens. The present study investigated the electrogenic transport (ΔIsc) of glucose, alanine and the dipeptide glycyl-l-glutamine (glygln), as well as glucose net flux rates in pig jejunal tissue after in vitro exposure to adult A. suum total ES or CSO antigens in Ussing chambers. ΔIsc of glucose, alanine and glucose net flux rate were significantly decreased after one hour of exposure to total ES antigen. In contrast, CSO antigens increased the transport of glygln. Additionally, nutrient uptake and ES antigen pattern were compared in culture medium from untreated adult worms and those with sealed mouth and anal openings. Untreated worms completely absorbed glucose, while cuticular absorption in sealed worms led to 90% reduction. Amino acid absorption was 30% less effective in sealed worms, and ammonia excretion decreased by 20%. Overall, the results show that A. suum total ES antigen rapidly impairs nutrient transport in vitro. Future studies confirming the results in vivo, narrowing down the ES components responsible and investigating underlying molecular mechanisms are needed.

Impact of helminth–microbiome interactions on childhood health and development—A clinical perspective

“…In rats, infection with the roundworm N. brasiliensis directly impaired glucose absorption in intestinal epithelial cells 119 . An in vitro study in pigs demonstrated that Ascaris suum not only directly absorbs glucose and amino acids into its own body, but also exposing porcine intestinal cells to A. suum excretory‐secretory products alone is sufficient to inhibit their absorption of glucose and alanine 120 . Intriguingly, treatment of roundworm‐infected pigs with the probiotic Bifidobacterium lactis attenuated the nutrient malabsorption induced by A. suum , 121 strongly implying that the Bifidobacterium genus has a universal beneficial effect on malnourishment.…”

“…119 An in vitro study in pigs demonstrated that Ascaris suum not only directly absorbs glucose and amino acids into its own body, but also exposing porcine intestinal cells to A. suum excretory-secretory products alone is sufficient to inhibit their absorption of glucose and alanine. 120 Intriguingly, treatment of roundworm-infected pigs with the probiotic Bifidobacterium lactis attenuated the nutrient malabsorption induced by A. suum, 121 strongly implying that the Bifidobacterium genus has a universal beneficial effect on malnourishment. Further investigation of the intersectionality of helminth infection and the GM in the context of malnutrition could unveil interesting, novel and cost-effective pre/pro-biotic co-therapies in an effort to combat the morbidities associated with global undernutrition.…”

Effects of adultAscaris suumand their antigens (total and trans-cuticular excretory–secretory antigen, cuticular somatic antigen) on intestinal nutrient transportin vivo

“…For Ussing chamber experiments, intestinal segments measuring 50 cm in length were taken directly distal of the aforementioned sampling sites, rinsed with ice-cold 0.9% NaCl and stored in Ussing buffer as previously described (Koehler et al, 2021a(Koehler et al, , 2021b.…”

“…at the end of the pre-patent period and therefore at a time point comparable to day 49 pi for A. suum (Schwarz et al ., 2011 ). When excretory–secretory (ES) antigens of adult A. suum were added to porcine jejunal mucosa in an in vitro set-up, an immediate impairment of glucose and alanine transport was evident (Koehler et al ., 2021 b ). Therefore, adult parasites may exhibit a stronger modulatory effect on the porcine mucosa as compared to larval or pre-adult parasite stages; however, this has not been investigated yet in vivo .…”

Modulation of the porcine intestinal microbiota in the course of Ascaris suum infection

“…For example, a 12% reduction in live weight gain was found in A. suum-infected versus anthelminthic-treated pigs in an outdoor system [10]. Reduced feed utilization efficiency is presumably due to a parasite-induced reduction in sodium-coupled intestinal glucose resorption [11][12][13][14]; however, alterations of the intestinal microbiota might also play a role. It has been suggested that A. suum actively manipulates its microbial environment by the release of potent antimicrobial proteins and peptides, thereby creating a favourable metabolic environment and immunoregulatory state [2,15].…”