Giardiasis is the most common waterborne parasitic infection of the human intestine worldwide. The etiological agent, Giardia duodenalis (syn. G. intestinalis, G. lamblia), is a flagellated, ...binucleated protozoan parasite which infects a wide array of mammalian hosts. Human giardiasis is a true cosmopolitan pathogen, with highest prevalence in developing countries. Giardiasis can present with a broad range of clinical manifestations from asymptomatic, to acute or chronic diarrheal disease associated with abdominal pain and nausea. Most infections are self-limiting, although re-infection and chronic infection can occur. Recent evidence indicating that Giardia may cause chronic post-infectious gastrointestinal complications have made it a topic of intense research. The causes of the post-infectious clinical manifestations due to Giardia, even after complete elimination of the parasite, remain obscure. This review offers a state-of-the-art discussion on the long-term consequences of Giardia infections, from extra-intestinal manifestations, growth and cognitive deficiencies, to post-infectious irritable bowel syndrome. The discussion also sheds light on some of the novel mechanisms recently implicated in the production of these post-infectious manifestations.
Giardiasis has been implicated in failure to thrive and growth retardation in children (Rogawski et al., 2017; Kosek et al., 2017). Because of its detrimental impact on health, giardiasis was ...included in the World Health Organization's "neglected disease initiative" (Savioli et al., 2006). Giardia may cause disease during the acute phase of the infection as well as post-infectiously, where it presents as post-infectious irritable bowel syndrome and chronic fatigue (Robertson et al., 2010; Hanevik et al., 2014). ...giardiasis can initiate a variety of extra-intestinal complications, including allergies, lower cognitive function, ocular pathologies, arthritis, and hypokalemic myopathy, and it has been associated with the development of cancer (Hardin et al., 1997; Halliez and Buret, 2013). ...mixed infections with different Giardia assemblages may worsen enterocyte apoptosis and tight junctional disruptions (Koh et al., 2013). Subsequent research then demonstrated that in patients with inflammatory bowel disease, the development of enhanced virulence by commensal bacteria required iron uptake from the gut lumen, allowing us to design novel therapeutic strategies (Motta et al., 2015, 2018).
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Exogenous factors that may influence the pathophysiology of Giardia infection remain incompletely understood. We have investigated the role of dietary fat in the pathogenesis of Giardia infection. ...Male 3 to 4-week-old C57BL/6 mice were fed either a low fat (LF) or a high fat (HF) diet for 12 days and challenged with G. duodenalis. In infected animals, the trophozoite burden was higher in HF + Giardia mice compared to the LF + Giardia group at day 7 post infection. Fatty acids exerted direct pro-growth effects on Giardia trophozoites. Analysis of disease parameters showed that HF + Giardia mice exhibited more mucosal infiltration by inflammatory cells, decreased villus/crypt ratios, goblet cell hyperplasia, mucus disruption, increased gut motility, and elevated fecal water content compared with LF + Giardia. HF diet-dependent exacerbation of Giardia-induced goblet cell hyperplasia was associated with elevated Atoh1 and Muc2 gene expression. Gut microbiota analysis revealed that the HF diet alone induces a taxonomic shift. HF + Giardia mice exhibited microbiota dysbiosis characterized by an increase of Firmicutes and a decrease of Bacteroidetes and significant changes in α- and β-diversity metrics. Taken together, the findings suggest that a HF diet exacerbates the outcome of Giardia infection. The data demonstrate that elevated dietary fat represents an important exogenous factor promoting the pathophysiology of giardiasis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Studies on the inhibition of inflammation by infection with helminth parasites have, until recently, overlooked a key determinant of health: the gut microbiota. Infection with helminths evokes ...changes in the composition of their host's microbiota: one outcome of which is an altered metabolome (e.g., levels of short-chain fatty acids (SCFAs)) in the gut lumen. The functional implications of helminth-evoked changes in the enteric microbiome (composition and metabolites) are poorly understood and are explored with respect to controlling enteric inflammation.
Antibiotic-treated wild-type, germ-free (GF) and free fatty-acid receptor-2 (ffar2) deficient mice were infected with the tapeworm Hymenolepis diminuta, then challenged with DNBS-colitis and disease severity and gut expression of the il-10 receptor-α and SCFA receptors/transporters assessed 3 days later. Gut bacteria composition was assessed by 16 s rRNA sequencing and SCFAs were measured. Other studies assessed the ability of feces or a bacteria-free fecal filtrate from H. diminuta-infected mice to inhibit colitis.
Protection against disease by infection with H. diminuta was abrogated by antibiotic treatment and was not observed in GF-mice. Bacterial community profiling revealed an increase in variants belonging to the families Lachnospiraceae and Clostridium cluster XIVa in mice 8 days post-infection with H. diminuta, and the transfer of feces from these mice suppressed DNBS-colitis in GF-mice. Mice treated with a bacteria-free filtrate of feces from H. diminuta-infected mice were protected from DNBS-colitis. Metabolomic analysis revealed increased acetate and butyrate (both or which can reduce colitis) in feces from H. diminuta-infected mice, but not from antibiotic-treated H. diminuta-infected mice. H. diminuta-induced protection against DNBS-colitis was not observed in ffar2
mice. Immunologically, anti-il-10 antibodies inhibited the anti-colitic effect of H. diminuta-infection. Analyses of epithelial cell lines, colonoids, and colon segments uncovered reciprocity between butyrate and il-10 in the induction of the il-10-receptor and butyrate transporters.
Having defined a feed-forward signaling loop between il-10 and butyrate following infection with H. diminuta, this study identifies the gut microbiome as a critical component of the anti-colitic effect of this helminth therapy. We suggest that any intention-to-treat with helminth therapy should be based on the characterization of the patient's immunological and microbiological response to the helminth.
Gastrointestinal biofilms in health and disease Motta, Jean-Paul; Wallace, John L; Buret, André G ...
Nature reviews. Gastroenterology & hepatology,
05/2021, Volume:
18, Issue:
5
Journal Article
Peer reviewed
Microorganisms colonize various ecological niches in the human habitat, as they do in nature. Predominant forms of multicellular communities called biofilms colonize human tissue surfaces. The ...gastrointestinal tract is home to a profusion of microorganisms with intertwined, but not identical, lifestyles: as isolated planktonic cells, as biofilms and in biofilm-dispersed form. It is therefore of major importance in understanding homeostatic and altered host-microorganism interactions to consider not only the planktonic lifestyle, but also biofilms and biofilm-dispersed forms. In this Review, we discuss the natural organization of microorganisms at gastrointestinal surfaces, stratification of microbiota taxonomy, biogeographical localization and trans-kingdom interactions occurring within the biofilm habitat. We also discuss existing models used to study biofilms. We assess the contribution of the host-mucosa biofilm relationship to gut homeostasis and to diseases. In addition, we describe how host factors can shape the organization, structure and composition of mucosal biofilms, and how biofilms themselves are implicated in a variety of homeostatic and pathological processes in the gut. Future studies characterizing biofilm nature, physical properties, composition and intrinsic communication could shed new light on gut physiology and lead to potential novel therapeutic options for gastrointestinal diseases.
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GEOZS, IJS, IMTLJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Gastrointestinal motility and transport of water and electrolytes play key roles in the pathophysiology of diarrhea upon exposure to enteric parasites. These processes are actively modulated by the ...enteric nervous system (ENS), which includes efferent, and afferent neurons, as well as interneurons. ENS integrity is essential to the maintenance of homeostatic gut responses. A number of gastrointestinal parasites are known to cause disease by altering the ENS. The mechanisms remain incompletely understood. Cryptosporidium parvum, Giardia duodenalis (syn. Giardia intestinalis, Giardia lamblia), Trypanosoma cruzi, Schistosoma species and others alter gastrointestinal motility, absorption, or secretion at least in part via effects on the ENS. Recent findings also implicate enteric parasites such as C. parvum and G. duodenalis in the development of post-infectious complications such as irritable bowel syndrome, which further underscores their effects on the gut-brain axis. This article critically reviews recent advances and the current state of knowledge on the impact of enteric parasitism on the neural control of gut functions, and provides insights into mechanisms underlying these abnormalities.
Irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal disorder. It is characterized by abdominal hypersensitivity, leading to discomfort and pain, as well as altered bowel ...habits. While it is common for IBS to develop following the resolution of infectious gastroenteritis then termed postinfectious IBS (PI-IBS), the mechanisms remain incompletely understood. Giardia duodenalis is a cosmopolitan water-borne enteropathogen that causes intestinal malabsorption, diarrhea, and postinfectious complications. Cause-and-effect studies using a human enteropathogen to help investigate the mechanisms of PI-IBS are sorely lacking. In an attempt to establish causality between giardiasis and postinfectious visceral hypersensitivity, this study describes a new model of PI-IBS in neonatal rats infected with G. duodenalis At 50 days postinfection with G. duodenalis (assemblage A or B), long after the parasite was cleared, rats developed visceral hypersensitivity to luminal balloon distension in the jejunum and rectum, activation of the nociceptive signaling pathway (increased c-fos expression), histological modifications (villus atrophy and crypt hyperplasia), and proliferation of mucosal intraepithelial lymphocytes and mast cells in the jejunum, but not in the rectum. G. duodenalis infection also disrupted the intestinal barrier, in vivo and in vitro, which in turn promoted the translocation of commensal bacteria. Giardia-induced bacterial paracellular translocation in vitro correlated with degradation of the tight junction proteins occludin and claudin-4. The extensive observations associated with gut hypersensitivity described here demonstrate that, indeed, in this new model of postgiardiasis IBS, alterations to the gut mucosa and c-fos are consistent with those associated with PI-IBS and, hence, offer avenues for new mechanistic research in the field.
(syn.
) is the protozoan parasite responsible for giardiasis, the most common and widely spread intestinal parasitic disease worldwide, affecting both humans and animals. After cysts ingestion ...(through either contaminated food or water),
excysts in the upper intestinal tract to release replicating trophozoites that are responsible for the production of symptoms. In the gut,
cohabits with the host's microbiota, and several studies have revealed the importance of this gut ecosystem and/or some probiotic bacteria in providing protection against
infection through mechanisms that remain incompletely understood. Recent findings suggest that Bile-Salt-Hydrolase (BSH)-like activities from the probiotic strain of
La1 may contribute to the anti-giardial activity displayed by this strain. Here, we cloned and expressed each of the three
genes present in the
La1 genome to study their enzymatic and biological properties. While BSH47 and BSH56 were expressed as recombinant active enzymes, no significant enzymatic activity was detected with BSH12.
assays allowed determining the substrate specificities of both BSH47 and BSH56, which were different. Modeling of these BSHs indicated a strong conservation of their 3-D structures despite low conservation of their primary structures. Both recombinant enzymes were able to mediate anti-giardial biological activity against
trophozoites
. Moreover, BSH47 exerted significant anti-giardial effects when tested in a murine model of giardiasis. These results shed new light on the mechanism, whereby active BSH derived from the probiotic strain
La1 may yield anti-giardial effects
and
. These findings pave the way toward novel approaches for the treatment of this widely spread but neglected infectious disease, both in human and in veterinary medicine.
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