Detangling the Crosstalk Between Ascaris, Trichuris and Gut Microbiota: What´s Next?

Abstract

Helminth infections remain a global public health issue, particularly in low- and middle-income countries, where roundworms from theTrichuris and Ascaris genera are most prevalent. These geohelminths not only impact human health but most importantly also affect animal well-being, in particular the swine industry. Host-helminth parasite interactions are complex and at the same time essential to understand the biology, dynamics and pathophysiology of these infections. Within these interactions, the immunomodulatory capacity of these helminths in the host has been extensively studied. Moreover, in recent years a growing interest on how helminths interact with the intestinal microbiota of the host has sparked, highlighting how this relationship plays an essential role in the establishment of initial infection, survival and persistence of the parasite, as well as in the development of chronic infections. Identifying the changes generated by these helminths on the composition and structure of the host intestinal microbiota constitutes a field of great scientific interest, since this can provide essential and actionable information for designing effective control and therapeutic strategies. Helminths like Trichuris and Ascaris are a focus of special importance due to their high prevalence, higher reinfection rates, resistance to anthelmintic therapy and unavailability of vaccines. Therefore, characterizing interactions between these helminths and the host intestinal microbiota represents an important approach to better understand the nature of this dynamic interface and explore novel therapeutic alternatives based on management of host microbiota. Given the extraordinary impact this may have from a biological, clinical, and epidemiological public health standpoint, this review aims to provide a comprehensive overview of current knowledge and future perspectives examining the parasite-microbiota interplay and its impact on host immunity.

Keywords: Ascaris; Trichuris; helminths; host-parasite interactions; microbiota.

Figure 1

Potential mechanisms of interaction between Trichuris and the host intestinal microbiota. (1) After ingestion of the infective stage of Trichuris, it has been demonstrated that certain bacteria, such as Escherichia coli, can improve the hatching of the eggs, contributing to the establishment of the infection and the development of the parasite. (2) The presence of eggs and released larval stages could cause changes by direct interaction with the host microbiota and by the inflammatory response generated by the parasite (3) Likewise, damage to the intestinal epithelium caused by Trichuris can cause translocation of bacteria into the intestinal lumen that may trigger localized inflammatory responses that could potentially affect certain commensal bacterial community of the microbiota influencing the composition and structures of the host bacterial communities. (4) The presence of the parasite in the intestine, together with the changes previously caused in the microbiota, generate an increase in oxygen availability and cause a decrease in strict anaerobic bacteria essential for intestinal health (such as Faecalibacterium) and facilitate the increase of facultative aerobes such as some Enterobacteriaceae that in turn contribute to the development of the infection. (5) Adult forms of Trichuris can generate Excretory/Secretory (E/S) products that, in addition to having an immunomodulatory effect, can have an impact on certain bacterial groups of the intestinal microbiota, modifying its structure and composition. (6) The adult forms produce eggs that that will be eliminated in the feces. Created with BioRender.com.

Figure 2

Potential mechanisms of interaction between Ascaris and the host intestinal microbiota. (1) After ingestion of the infecting stage of Ascaris, L3 larvae are released from embryonated eggs into the host intestine. (2) These larvae can have an effect by direct interactions on the intestinal microbiota and thus propitiate an increase in oxygen availability that promote the increase of facultative aerobic bacteria and the decrease of strict anaerobic bacteria necessary for an adequate intestinal health, generating a disruption of the host microbiota. (3) Additionally, within the life cycle of Ascaris, damage to the intestinal epithelium caused to continue its migration produces the translocation of bacteria into the intestinal lumen, that may trigger localized inflammatory responses that could potentially affect certain commensal bacterial community of the microbiota influencing the composition and structures of the host bacterial communities (4) Migration of Ascaris L3 larvae to the liver and subsequently (5) from the liver to the lungs, allowing Ascaris to complete later phases of its life cycle, generating, among other things, inflammatory processes at the level of the pulmonary tissue characterized by a high infiltration of eosinophils and clinical symptoms such as those evidenced in Loeffler’s Syndrome. (6) Larvae released from the lung can migrate back to the intestine and transform into L4, for later completing their development into adult forms. (7) These adult forms have the property of generating Excretory/Secretory (E/S) products and other metabolites with great immunomodulatory capacity, and also with antimicrobial function, such as ASABF inducers and Cecropin P1 to P4 proteins, that can modify the structure and composition of the host intestinal microbiota. (8) Finally, in an environment with now beneficial conditions for Ascaris, the adult forms have the ability to produce eggs that will be eliminated in the feces to continue its life cycle and infection process. Created with BioRender.com.

Figure 3

Methodological approaches for the study of parasite-microbiota-host interactions. Studies in humans and in animal models, such as murine and porcine models, facilitate the evaluation of helminth-host microbiota interactions from different approaches such as: (i) metagenomic approaches by means of second and third generation sequencing, (ii) approaches based on transcriptomics and spatial transcriptomics and (iii) metabolomic approaches based on techniques such as mass spectrometry.