Text Box 4.

Therapeutic perspectives.

Targeting the GM and tweaking the cross talk between bacteria, protozoans and helminths is regarded as a prospective therapeutic strategy for the treatment of several pathologies. In the case of pathogenic protozoan invasions, for example, E. histolytica, G. duodenalis, Cryptosporidium spp. or Toxoplasma spp., interventions such as probiotics, prebiotics or fecal microbiota transplantation (FMT) can be introduced to enhance microbiota diversity and change the course of pathogenesis and the disease outcomes in the host. 76 In addition, protozoans such as Blastocystis spp. can be a likely therapeutic choice in treating chronic inflammatory conditions as they exhibit the anti-inflammatory potential and is seen to increase the bacterial diversity. 28 Lately, the therapeutic use of helminths has gained a lot of attention. This is popularly known as “helminth therapy” (HT) which demonstrates the innate ability of helminths to alter immune response from Th1 to Th2/Treg. 77 HT and helminth-derived product therapy (HDPT) utilizes live helminths and ESP components for immuno-modulation. Many animal studies have shown promising results to treat or prevent inflammatory diseases such as IBD, T1D, MS, rheumatoid arthritis (RA) and asthma. For example, schistosome glutathione S-transferase (P28GST) improves intestinal inflammation in experimental colitis and Fasciola hepatica mitigates experimental autoimmune encephalomyelitis (EAE) and MS. 77 Similarly, ES-62, a glycoprotein from the filarial nematode Acanthocheilonema vitae, is a potent pharmacological molecule that can be used for asthma, lung fibrosis and RA. 78 Likewise, metabolism and weight regulation are in part immunologically regulated, hence helminth infections such as Nippostrongylus brasiliensis and S. mansoni, once again display a therapeutic perspective since it was shown that they prevent glucose intolerance through adipose tissue eosinophils and type 2 macrophages activation. 37 Furthermore, a number of animal studies have evidenced that helminth infections (S. mansoni, Trichinella spiralis and Filaria spp.,) and helminth derived products can prevent onset or cure T1D, possibly by repressing Th1 immune response. 79 In cases where parasite worms worsen the diagnosis, such as H. polygyrus in Citrobacter colitis, 26 the parasite itself could be targeted in therapy. Another interesting scenario is the proposition of T. musculis as a “protistic antibiotic” as its protection against Salmonella infection through IL-18 pathways has already been shown.58,31 Although helminth based therapies seem transcendental and few human trials are underway, several hurdles remain. 77 One of the major shortcoming is the tumor promoting activity of ESPs. 80 Moreover, the use of live helminths remain contentious because of the lack of comprehensive understanding of mechanism of disease prevention and inhibition.