COVID-19 morbidity in lower versus higher income populations underscores the need to restore lost biodiversity of eukaryotic symbionts

The avoidance of infectious disease by widespread use of ‘systems hygiene’, defined by hygiene-enhancing technology such as sewage systems, water treatment facilities, and secure food storage containers, has led to a dramatic decrease in symbiotic helminths and protists in high-income human populations. Over a half-century of research has revealed that this ‘biota alteration’ leads to altered immune function and a propensity for chronic inflammatory diseases, including allergic, autoimmune and neuropsychiatric disorders. A recent Ethiopian study (EClinicalMedicine 39: 101054), validating predictions made by several laboratories, found that symbiotic helminths and protists were associated with a reduced risk of severe COVID-19 (adjusted odds ratio = 0.35; p<0.0001). Thus, it is now apparent that ‘biome reconstitution’, defined as the artificial re-introduction of benign, symbiotic helminths or protists into the ecosystem of the human body, is important not only for alleviation of chronic immune disease, but likely also for pandemic preparedness

Wild chimpanzees are infected by Trypanosoma brucei

AbstractAlthough wild chimpanzees and other African great apes live in regions endemic for African sleeping sickness, very little is known about their trypanosome infections, mainly due to major difficulties in obtaining their blood samples. In present work, we established a diagnostic ITS1-based PCR assay that allows detection of the DNA of all four Trypanosoma brucei subspecies (Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense, Trypanosoma brucei gambiense, and Trypanosoma brucei evansi) in feces of experimentally infected mice. Next, using this assay we revealed the presence of trypanosomes in the fecal samples of wild chimpanzees and this finding was further supported by results obtained using a set of primate tissue samples. Phylogenetic analysis of the ITS1 region showed that the majority of obtained sequences fell into the robust T. brucei group, providing strong evidence that these infections were caused by T. b. rhodesiense and/or T. b. gambiense. The optimized technique of trypanosome detection in feces will improve our knowledge about the epidemiology of trypanosomes in primates and possibly also other endangered mammals, from which blood and tissue samples cannot be obtained.Finally, we demonstrated that the mandrill serum was able to efficiently lyse T. b. brucei and T. b. rhodesiense, and to some extent T. b. gambiense, while the chimpanzee serum failed to lyse any of these subspecies

Identification of potentially zoonotic parasites in captive orangutans and semi-captive mandrills: phylogeny and morphological comparison

Cysts and trophozoites of vestibuliferid ciliates and larvae of Strongyloides were found in fecal samples from captive orangutans Pongo pygmaeus and P. abelii from Czech and Slovak zoological gardens. As comparative material, ciliates from semi-captive mandrills Mandrillus sphinx from Gabon were included in the study. Phylogenetic analysis of the detected vestibuliferid ciliates using ITS1-5.8s-rRNA-ITS2 and partial 18S rDNA revealed that the ciliates from orangutans are conspecific with Balantioides coli lineage A, while the ciliates from mandrills clustered with Buxtonella-like ciliates from other primates. Morphological examination of the cysts and trophozoites using light microscopy did not reveal differences robust enough to identify the genera of the ciliates. Phylogenetic analysis of detected L1 larvae of Strongyloides using partial cox1 revealed Strongyloides stercoralis clustering within the cox1 lineage A infecting dogs, humas and other primates. The sequences of 18S rDNA support these results. As both B. coli and S. stercoralis are zoonotic parasites and the conditions in captive and semi-captive settings may facilitate transmission to humans, prophylactic measures should reflect the findings

Helminth Interactions with Bacteria in the Host Gut Are Essential for Its Immunomodulatory Effect

Colonization by the benign tapeworm, Hymenolepis diminuta, has been associated with a reduction in intestinal inflammation and changes in bacterial microbiota. However, the role of microbiota in the tapeworm anti-inflammatory effect is not yet clear, and the aim of this study was to determine whether disruption of the microflora during worm colonization can affect the course of intestinal inflammation. We added a phase for disrupting the intestinal microbiota using antibiotics to the experimental design for which we previously demonstrated the protective effect of H. diminuta. We monitored the immunological markers, clinical parameters, bacterial microbiota, and histological changes in the colon of rats. After a combination of colonization, antibiotics, and colitis induction, we had four differently affected experimental groups. We observed a different course of the immune response in each group, but no protective effect was found. Rats treated with colonization and antibiotics showed a strong induction of the Th2 response as well as a significant change in microbial diversity. The microbial results also revealed differences in the richness and abundance of some bacterial taxa, influenced by various factors. Our data suggest that interactions between the tapeworm and bacteria may have a major impact on its protective effect.Science, Faculty ofNon UBCBotany, Department ofReviewedFacult

Comparison of molecular diagnostic approaches for the detection and differentiation of the intestinal protist

Blastocystis is the most commonly found intestinal protist in the world. Accurate detection and differentiation of Blastocystis including its subtypes (arguably species) are essential to understand its epidemiology and role in human health. We compared (i) the sensitivity of conventional PCR (cPCR) and qPCR in a set of 288 DNA samples obtained from stool samples of gut-healthy individuals, and (ii) subtype diversity as detected by next-generation sequencing (NGS) versus Sanger sequencing. Real-time PCR resulted in more positive samples than cPCR, revealing high fecal load of Blastocystis based on the quantification curve in most samples. In subtype detection, NGS was largely in agreement with Sanger sequencing but showed higher sensitivity for mixed subtype colonization within one host. This fact together with use of the combination of qPCR and NGS and obtaining information on the fecal protist load will be beneficial for epidemiological and surveillance studies

Are Human Intestinal Eukaryotes Beneficial or Commensals? - Fig 1

<p>Representative protist symbionts that are part of the human gut eukaryome: (A) Stramenopile <i>Blastocystis hominis</i>; (B) diplomonadid <i>Enteromonas hominis</i>; (C) retortamonadid <i>Retortamonas intestinalis</i>; (D) trichomonadid <i>Pentratrichomonas hominis</i>; (E) tritrichomonadid <i>Dientamoeba fragilis</i>; (F) retortamonadid <i>Chilomastix mesnili</i>; (G) amoebozoans <i>Entamoeba hartmani</i>; (H) <i>Endolimax nana</i>; (I) <i>Entamoeba coli</i>; (J) <i>Entamoeba dispar</i>; (K) coccidian <i>Isospora belli</i>; (L) amoebozoan <i>Iodamoeba buetschli</i>; (M) microsporidian <i>Encephalitozoon cuniculi</i>; (N) ascomycete <i>Candida albicans</i>. Magnification is to the same scale (scale bar = 5 μm). Living cells (A,J–M), protargol-stained cells (B–D,F), trichrome-stained cell (E), Giemsa-stained cell (G), iodine-stained cell (H), and Gomori trichrome-stained cell (I). Pictures were kindly provided by K. Jirků-Pomajbíková (A,I,L), Ivan Čepička (B,C,E,F) (Charles University, Prague), Jaroslav Kulda (D) (Charles University, Prague), Marianne Lebbad (G,H) (Public Health Agency, Solna, Sweden), Martin Kostka (I) (University of South Bohemia, České Budějovice), Jiří Vávra (K) (Charles University, Prague), Martin Kváč and Bohouš Sak (M) (Institute of Parasitology, České Budějovice), and Miroslav Kolařík (N) (Institute of Microbiology, Prague).</p

A benign helminth alters the host immune system and the gut microbiota in a rat model system

<div><p>Helminths and bacteria are major players in the mammalian gut ecosystem and each influences the host immune system and health. Declines in helminth prevalence and bacterial diversity appear to play a role in the dramatic rise of immune mediated inflammatory diseases (IMIDs) in western populations. Helminths are potent modulators of immune system and their reintroduction is a promising therapeutic avenue for IMIDs. However, the introduction of helminths represents a disturbance for the host and it is important to understand the impact of helminth reintroduction on the host, including the immune system and gut microbiome. We tested the impact of a benign tapeworm, <i>Hymenolepis diminuta</i>, in a rat model system. We find that <i>H</i>. <i>diminuta</i> infection results in increased interleukin 10 gene expression in the beginning of the prepatent period, consistent with induction of a type 2 immune response. We also find induction of humoral immunity during the patent period, shown here by increased IgA in feces. Further, we see an immuno-modulatory effect in the small intestine and spleen in patent period, as measured by reductions in tissue immune cells. We observed shifts in microbiota community composition during the patent period (beta-diversity) in response to <i>H</i>. <i>diminuta</i> infection. However, these compositional changes appear to be minor; they occur within families and genera common to both treatment groups. There was no change in alpha diversity. <i>Hymenolepis diminuta</i> is a promising model for helminth therapy because it establishes long-term, stable colonization in rats and modulates the immune system without causing bacterial dysbiosis. These results suggest that the goal of engineering a therapeutic helminth that can safely manipulate the mammalian immune system without disrupting the rest of the gut ecosystem is in reach.</p></div

List of anti-rat antibodies used in flow cytometry analyses.

<p>List of anti-rat antibodies used in flow cytometry analyses.</p

Flow cytometry boxplot panel figure—general leukocyte populations.

<p>Abundance of leukocyte populations in flow cytometric samples from rats infected with <i>Hymenolepis diminuta</i> (dark grey, n = 4) and control rats (light grey, n = 4). The error bars represent the 95% confidence intervals for the mean cell counts at each sample location for each group. The asterisks represent a significant difference in the mean cell counts at α = 0.05 level for t-tests implemented at each time point. (*): 0.01 ≤ p < 0.05, (**): 0.001< p < 0.01. [the numbers of cells are in the chart are given in 10⁴ in duodenum & ileum, colon, in case of spleen in 10⁶].</p