RESUMO
There is rapidly growing awareness of microbiome assembly and function in early-life gut health. Although many factors, such as antibiotic use and highly processed diets, impinge on this process, most research has focused on people residing in high-income countries. However, much of the world's population lives in low- and middle-income countries (LMICs), where, in addition to erratic antibiotic use and suboptimal diets, these groups experience unique challenges. Indeed, many children in LMICs are infected with intestinal helminths. Although helminth infections are strongly associated with diverse developmental co-morbidities and induce profound microbiome changes, few studies have directly examined whether intersecting pathways between these components of the holobiont shape health outcomes in early life. Here, we summarize microbial colonization within the first years of human life, how helminth-mediated changes to the gut microbiome may affect postnatal growth, and why more research on this relationship may improve health across the lifespan.
Assuntos
Microbioma Gastrointestinal , Helmintíase , Helmintos , Animais , Humanos , Lactente , Helmintíase/microbiologia , Helmintos/fisiologia , Enteropatias ParasitáriasRESUMO
High-throughput 16S rRNA sequencing has allowed the characterization of helminth-uninfected (HU) and helminth-infected (HI) gut microbiomes, revealing distinct profiles. However, there have been no qualitative or quantitative syntheses of these studies, which show marked variation in participant age, diet, pathogen of interest, and study location. A predefined minimally biased search strategy identified 23 studies in humans. For each of these studies, we qualitatively addressed the effects of helminth infection on within-individual (alpha) and between-individual (beta) fecal microbiome diversity, infection-associated microbial taxa, the effect of helminth clearance on microbiome composition, microbiome composition as a predictor of infection status or treatment outcome, and treatment-specific effects on the fecal microbiome. Concomitantly, we performed a meta-analysis on a subset of 7 of these studies containing raw, paired-end 16S reads and individual-level metadata, comprising 424 pretreatment or untreated HI individuals and 497 HU controls. After reducing the batch effect and adjusting for age, our data demonstrated that intestinal helminth parasites can alter the host gut microbiome by increasing alpha diversity and promoting taxonomic reassortment and gradient collapse. Most strongly influencing the microbiome composition were the helminths found in the large intestine, Enterobius vermicularis and Trichuris trichiura, suggesting that this influence appears to be specific to soil-transmitted helminths (STH) species and host anatomical niche. In summary, using a large and diverse sample set captured in the meta-analysis, we were able to evaluate the influence of individual helminth species as well as species-species interactions, each of which explained a significant portion of the variation in the microbiome. IMPORTANCE The gut microbiome has established importance in regulating many aspects of human health, including nutrition and immunity. While many internal and environmental factors are known to influence the microbiome, less is known about the effects of intestinal helminth parasites (worms), which together affect one-sixth of the world's population. Through a comprehensive qualitative systematic review and quantitative meta-analysis of existing literature, we provide strong evidence that helminth infection dynamically shifts the intestinal microbiome structure. Moreover, we demonstrated that such influence seems to be specific to helminth species and host anatomical niche. Our findings suggest that the gut microbiome may underlie some of the pathology associated with intestinal worm infection and support future work to understand the precise nature of the helminth-microbiome relationship.
Assuntos
Bactérias/classificação , Bactérias/isolamento & purificação , Disbiose/microbiologia , Microbioma Gastrointestinal , Helmintíase/microbiologia , Helmintos/fisiologia , Adolescente , Adulto , Idoso , Animais , Bactérias/genética , Criança , Pré-Escolar , Disbiose/parasitologia , Fezes/parasitologia , Feminino , Helmintíase/parasitologia , Helmintos/classificação , Helmintos/genética , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Filogenia , Adulto JovemRESUMO
Helminth infections impact the composition of the mammalian gut microbiota; however, the mechanisms underpinning these interactions are, thus far, unknown. In this article, we propose that microbiota-derived extracellular vesicles might represent key players in host-helminth-microbiome crosstalk, and outline future directions to elucidate their role(s) in host-parasite relationships.
Assuntos
Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/parasitologia , Microbioma Gastrointestinal/fisiologia , Helmintíase/microbiologia , Helmintíase/parasitologia , Interações Hospedeiro-Parasita , Animais , Helmintos/fisiologia , HumanosRESUMO
Infection with Streptococcus pneumoniae is the leading cause of death in children and burden of disease is greatest where helminth infections are also common. We investigated the impact of intestinal helminth co-infection on pneumococcal carriage; a risk factor for invasive disease. We used a mouse co-infection model and clinical data to assess the impact of co-infection on carriage density. Co-infection in mice was associated with increased pneumococcal carriage density and dissemination into lungs. Helminth-infected children also exhibited increased carriage density as compared to uninfected children. Anthelmintic treatment may be a cost-effective method of reducing pneumococcal disease burden in lower-income countries.
Assuntos
Coinfecção/microbiologia , Helmintíase/microbiologia , Enteropatias Parasitárias/microbiologia , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Animais , Criança , Pré-Escolar , Coinfecção/epidemiologia , Equador/epidemiologia , Feminino , Helmintíase/epidemiologia , Humanos , Enteropatias Parasitárias/epidemiologia , Masculino , Camundongos , Infecções Pneumocócicas/epidemiologia , Fatores de RiscoAssuntos
Coinfecção , Gastrite/microbiologia , Infecções por Helicobacter , Helicobacter pylori , Enteropatias Parasitárias/complicações , Gastrite/complicações , Gastrite/imunologia , Microbioma Gastrointestinal , Helmintíase/complicações , Helmintíase/imunologia , Helmintíase/microbiologia , Humanos , Enteropatias Parasitárias/imunologia , Enteropatias Parasitárias/microbiologia , Células Th1/imunologia , Células Th2/imunologiaRESUMO
Intestinal helminth parasites present major challenges to the welfare of humans and threaten the global food supply. While the discovery of anthelminthic drugs empowered our ability to offset these harms to society, the alarming rise of anthelminthic drug resistance mitigates contemporary efforts to treat and control intestinal helminthic infections. Fortunately, emerging research points to potential opportunities to combat anthelminthic drug resistance by harnessing the gut microbiome as a resource for discovering novel therapeutics and informing responsible drug administration. In this review, we highlight research that demonstrates this potential and provide rationale to support increased investment in efforts to uncover and translationally utilize knowledge about how the gut microbiome mediates intestinal helminthic infection and its outcomes.
Assuntos
Anti-Helmínticos/farmacologia , Resistência a Medicamentos , Microbioma Gastrointestinal , Helmintíase/tratamento farmacológico , Helmintos/efeitos dos fármacos , Enteropatias Parasitárias/tratamento farmacológico , Animais , Helmintíase/microbiologia , Helmintíase/parasitologia , Helmintos/genética , Helmintos/fisiologia , Humanos , Enteropatias Parasitárias/microbiologia , Enteropatias Parasitárias/parasitologiaRESUMO
BACKGROUND: The complex network of interactions occurring between gastrointestinal (GI) and extra-intestinal (EI) parasitic helminths of humans and animals and the resident gut microbial flora is attracting increasing attention from biomedical researchers, because of the likely implications for the pathophysiology of helminth infection and disease. Nevertheless, the vast heterogeneity of study designs and microbial community profiling strategies, and of bioinformatic and biostatistical approaches for analyses of metagenomic sequence datasets hinder the identification of bacterial targets for follow-up experimental investigations of helminth-microbiota cross-talk. Furthermore, comparative analyses of published datasets are made difficult by the unavailability of a unique repository for metagenomic sequence data and associated metadata linked to studies aimed to explore potential changes in the composition of the vertebrate gut microbiota in response to GI and/or EI helminth infections. RESULTS: Here, we undertake a meta-analysis of available metagenomic sequence data linked to published studies on helminth-microbiota cross-talk in humans and veterinary species using a single bioinformatic pipeline, and introduce the 'MICrobiome HELminth INteractions database' (MICHELINdb), an online resource for mining of published sequence datasets, and corresponding metadata, generated in these investigations. CONCLUSIONS: By increasing data accessibility, we aim to provide the scientific community with a platform to identify gut microbial populations with potential roles in the pathophysiology of helminth disease and parasite-mediated suppression of host inflammatory responses, and facilitate the design of experiments aimed to disentangle the cause(s) and effect(s) of helminth-microbiota relationships. Video abstract.
Assuntos
Microbioma Gastrointestinal , Helmintos/genética , Helmintos/fisiologia , Microbiota/genética , Microbiota/fisiologia , Software , Animais , Bactérias/genética , Bactérias/metabolismo , Mineração de Dados , Conjuntos de Dados como Assunto , Fezes/microbiologia , Helmintíase/microbiologia , Helmintíase/parasitologia , Helmintíase Animal/microbiologia , Humanos , Enteropatias Parasitárias/parasitologia , Metagenoma , RNA Ribossômico 16S/genéticaRESUMO
Helminth infection and dietary intake can affect the intestinal microbiota, as well as the immune system. Here we analyzed the relationship between fecal microbiota and blood profiles of indigenous Malaysians, referred to locally as Orang Asli, in comparison to urban participants from the capital city of Malaysia, Kuala Lumpur. We found that helminth infections had a larger effect on gut microbial composition than did dietary intake or blood profiles. Trichuris trichiura infection intensity also had the strongest association with blood transcriptional profiles. By characterizing paired longitudinal samples collected before and after deworming treatment, we determined that changes in serum zinc and iron levels among the Orang Asli were driven by changes in helminth infection status, independent of dietary metal intake. Serum zinc and iron levels were associated with changes in the abundance of several microbial taxa. Hence, there is considerable interplay between helminths, micronutrients and the microbiota on the regulation of immune responses in humans.
Assuntos
Dieta , Microbioma Gastrointestinal , Helmintíase/sangue , Helmintíase/microbiologia , Interações Hospedeiro-Parasita/fisiologia , Humanos , Ferro/sangue , Malásia , RNA/sangue , Zinco/sangueRESUMO
Intestinal helminth infections elicit Th2-type immunity, which influences host immune responses to additional threats, such as allergens, metabolic disease, and other pathogens. Th2 immunity involves a shift of the CD4+ T-cell population from type-0 to type-2 (Th2) with increased abundance of interleukin (IL)-4 and IL-13. This study sought to investigate if existing gut-restricted intestinal helminth infections impact bacterial-induced acute airway neutrophil recruitment. C57BL/6 mice were divided into four groups: uninfected; helminth-Heligmosomoides polygyrus infected; Pseudomonas aeruginosa infected; and coinfected. Mice infected with H. polygyrus were incubated for 2 weeks, followed by P. aeruginosa intranasal inoculation. Bronchial alveolar lavage, blood, and lung samples were analyzed. Interestingly, infection with gut-restricted helminths resulted in immunological and structural changes in the lung. These changes include increased lung CD4+ T cells, increased Th2 cytokine expression, and airway goblet cell hyperplasia. Furthermore, coinfected mice exhibited significantly more airspace neutrophil infiltration at 6 hours following P. aeruginosa infection and exhibited an improved rate of survival compared with bacterial infected alone. These results suggest that chronic helminth infection of the intestines can influence and enhance acute airway neutrophil responses to P. aeruginosa infection.
Assuntos
Helmintíase/patologia , Enteropatias Parasitárias/patologia , Pulmão/microbiologia , Nematospiroides dubius/isolamento & purificação , Neutrófilos/imunologia , Pseudomonas aeruginosa/metabolismo , Animais , Helmintíase/imunologia , Helmintíase/microbiologia , Mediadores da Inflamação/metabolismo , Enteropatias Parasitárias/imunologia , Enteropatias Parasitárias/microbiologia , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Nematospiroides dubius/patogenicidade , Células Th2/imunologiaRESUMO
A plethora of data points towards a role of the gastrointestinal (GI) microbiota of neonatal and young vertebrates in supporting the development and regulation of the host immune system. However, knowledge of the impact that infections by GI helminths exert on the developing microbiota of juvenile hosts is, thus far, limited. This study investigates, for the first time, the associations between acute infections by GI helminths and the faecal microbial and metabolic profiles of a cohort of equine youngstock, prior to and following treatment with parasiticides (ivermectin). We observed that high versus low parasite burdens (measured via parasite egg counts in faecal samples) were associated with specific compositional alterations of the developing microbiome; in particular, the faecal microbiota of animals with heavy worm infection burdens was characterised by lower microbial richness, and alterations to the relative abundances of bacterial taxa with immune-modulatory functions. Amino acids and glucose were increased in faecal samples from the same cohort, which indicated the likely occurrence of intestinal malabsorption. These data support the hypothesis that GI helminth infections in young livestock are associated with significant alterations to the GI microbiota, which may impact on both metabolism and development of acquired immunity. This knowledge will direct future studies aimed to identify the long-term impact of infection-induced alterations of the GI microbiota in young livestock.
Assuntos
Disbiose/microbiologia , Disbiose/parasitologia , Helmintíase/microbiologia , Helmintos/parasitologia , Herbivoria/fisiologia , Cavalos/parasitologia , Animais , Disbiose/tratamento farmacológico , Fezes/parasitologia , Feminino , Microbioma Gastrointestinal/fisiologia , Helmintíase/tratamento farmacológico , Helmintos/efeitos dos fármacos , Ivermectina/farmacologia , MasculinoRESUMO
Species richness and composition are central themes in community ecology of helminths because they improve the understanding of factors that determine community structure. Floodplain ecosystems and the environmental alterations induced by hydrological cycles are factors that maintain biodiversity over time, as observed in the Upper Paraná River floodplain, where the individuals of Brycon orbignyanus were collected. The objective of this study was to evaluate whether variables such as the richness and abundance of endoparasites are related to the fish size during different hydrological periods (high and low waters). A total of 163 endoparasites belonging to 13 species were collected in the 104 fish examined. Fish size had a positive correlation with mean diversity and abundance of the endoparasite infracommunity, supporting the idea that larger hosts are able to harbor a more abundant and diverse parasite infracommunity. The diversity of habitats provided by the floodplain can be considered the main factor explaining the differences between these attributes of parasite species. Variations in parasite richness between different hosts provide not only a good model for studies on community diversification but are also of great interest in species conservation. All parasite species found in B. orbignyanus were recorded for the first time in this host, especially in the Upper Paraná River floodplain.
Assuntos
Animais , Characidae/parasitologia , Estações Hidrológicas , Helmintíase/microbiologiaRESUMO
There is increasing attention on the complex interactions occurring between gastrointestinal parasitic helminths and the microbial flora (microbiota) inhabiting the host gut. However, little is known about the occurrence, structure, and function of microbial populations residing within parasite organs and tissues. In this article, we argue that an in-depth understanding of the interplay between parasites and their microbiomes may significantly enhance current knowledge of parasite biology and physiology, and may lead to the discovery of entirely novel, anthelmintic-independent interventions against parasites and parasitic diseases.
Assuntos
Microbioma Gastrointestinal , Helmintíase/microbiologia , Helmintos/microbiologia , Interações Hospedeiro-Parasita , Animais , Humanos , Microbiota/fisiologiaRESUMO
Whilst a wealth of data indicate that infections by gastrointestinal helminths are accompanied by significant alterations in the composition of the vertebrate gut flora, little is known of the immune-molecular mechanisms that regulate host-parasite-microbiota interactions. 'Traditional' experimental models of gastrointestinal helminthiases, in which the role(s) of each of the components of this triad can be tested, provide an opportunity to advance research in this area. In this article, we propose the Echinostoma caproni-mouse system as a potentially useful tool for studies of the role of the host gut microbiota in preventing pathology and inducing parasite clearance via interleukin (IL)-25, an epithelial-derived alarmin with key roles in antihelminth immunity and maintenance of gut homeostasis.
Assuntos
Helmintíase , Interações Hospedeiro-Parasita/imunologia , Modelos Biológicos , Animais , Helmintíase/imunologia , Helmintíase/microbiologia , HumanosRESUMO
Se presentan los casos de dos niños, hermanos, de los cuales se recibieron muestras de heces fecales en el laboratorio de microbiología del municipio Güines, provincia Mayabeque. Las muestras contenían minúsculos proglótides, que resultaron ser de Inermicapsifer madagascariensis. Luego del tratamiento con praziquantel 10 mg/kg en dosis única, orientado por el servicio de pediatría, se confirmó la expulsión de restos del parásito y la curación de dicha infección, tras resultados negativos por controles repetitivos de heces fecales durante seis meses. Se decide publicar estos raros casos diagnosticados y estimular estudios de campo que permitan completar el ciclo evolutivo de este parásito(AU)
We are presenting the cases of two sibling children, from whom samples of faeces were received in the microbiology laboratory of the Güines municipality, Mayabeque province. The samples contained tiny proglottids, which turned out to be from Inermicapsifer madagascariensis. After treatment with Praziquantel 10 mg/kg in a single dose, guided by the pediatric service, the expulsion of parasite remains and the cure of this infection were confirmed, after negative results due to repetitive controls of faecal stools for six months. It is decided to publish these rare diagnosed cases and stimulate field studies to complete the evolutionary cycle of this parasite(AU)
Assuntos
Humanos , Masculino , Lactente , Pré-Escolar , Praziquantel/uso terapêutico , Técnicas de Laboratório Clínico/métodos , Helmintíase/microbiologiaRESUMO
Investigations of the impact that patent infections by soil-transmitted gastrointestinal nematode parasites exert on the composition of the host gut commensal flora are attracting growing interest by the scientific community. However, information collected to date varies across experiments, and further studies are needed to identify consistent relationships between parasites and commensal microbial species. Here, we explore the qualitative and quantitative differences between the microbial community profiles of cohorts of human volunteers from Sri Lanka with patent infection by one or more parasitic nematode species (H+), as well as that of uninfected subjects (H-) and of volunteers who had been subjected to regular prophylactic anthelmintic treatment (Ht). High-throughput sequencing of the bacterial 16S rRNA gene, followed by bioinformatics and biostatistical analyses of sequence data revealed no significant differences in alpha diversity (Shannon) and richness between groups (P = 0.65, P = 0.13 respectively); however, beta diversity was significantly increased in H+ and Ht when individually compared to H-volunteers (P = 0.04). Among others, bacteria of the families Verrucomicrobiaceae and Enterobacteriaceae showed a trend towards increased abundance in H+, whereas the Leuconostocaceae and Bacteroidaceae showed a relative increase in H- and Ht respectively. Our findings add valuable knowledge to the vast, and yet little explored, research field of parasite-microbiota interactions and will provide a basis for the elucidation of the role such interactions play in pathogenic and immune-modulatory properties of parasitic nematodes in both human and animal hosts.
Assuntos
Biodiversidade , Fezes/microbiologia , Microbioma Gastrointestinal , Helmintíase/microbiologia , Helmintíase/parasitologia , Helmintos , Enteropatias Parasitárias/microbiologia , Análise de Variância , Animais , Biologia Computacional/métodos , Humanos , Metagenoma , Metagenômica/métodos , Sri LankaRESUMO
Parasitic nematode infections are widespread in nature, affecting humans as well as wild, companion, and livestock animals. Most parasitic nematodes inhabit the intestines of their hosts living in close contact with the intestinal microbiota. Many species also have tissue migratory life stages in the absence of severe systemic inflammation of the host. Despite the close coexistence of helminths with numerous microbes, little is known concerning these interactions. While the environmental niche is considerably different, the free-living nematode Caenorhabditis elegans (C. elegans) is also found amongst a diverse microbiota, albeit on decaying organic matter. As a very well characterized model organism that has been intensively studied for several decades, C. elegans interactions with bacteria are much more deeply understood than those of their parasitic counterparts. The enormous breadth of understanding achieved by the C. elegans research community continues to inform many aspects of nematode parasitology. Here, we summarize what is known regarding parasitic nematode-bacterial interactions while comparing and contrasting this with information from work in C. elegans. This review highlights findings concerning responses to bacterial stimuli, antimicrobial peptides, and the reciprocal influences between nematodes and their environmental bacteria. Furthermore, the microbiota of nematodes as well as alterations in the intestinal microbiota of mammalian hosts by helminth infections are discussed.
Assuntos
Microbiologia Ambiental , Microbioma Gastrointestinal/fisiologia , Interações Hospedeiro-Parasita/fisiologia , Intestinos/microbiologia , Nematoides/microbiologia , Animais , Fenômenos Fisiológicos Bacterianos , Biodiversidade , Caenorhabditis elegans/microbiologia , Caenorhabditis elegans/fisiologia , Resistência Microbiana a Medicamentos , Fezes/microbiologia , Microbioma Gastrointestinal/imunologia , Helmintíase/microbiologia , Helmintos/microbiologia , Interações Hospedeiro-Parasita/efeitos dos fármacos , Interações Hospedeiro-Parasita/imunologia , Humanos , Modelos Biológicos , Nematoides/classificação , Nematoides/efeitos dos fármacos , Nematoides/imunologia , Transdução de SinaisRESUMO
BACKGROUND: Bidirectional signalling between the brain and the gastrointestinal tract is regulated at neural, hormonal, and immunological levels. Recent studies have shown that helminth infections can alter the normal gut microbiota. Studies have also shown that the gut microbiota is instrumental in the normal development, maturation and function of the brain. The pathophysiological pathways by which helminth infections contribute to altered cognitive function remain poorly understood. DISCUSSION: We put forward the hypothesis that gastrointestinal infections with parasitic worms, such as helminths, induce an imbalance of the gut-brain axis, which, in turn, can detrimentally manifest in brain development. Factors supporting this hypothesis are: 1) research focusing on intelligence and school performance in school-aged children has shown helminth infections to be associated with cognitive impairment, 2) disturbances in gut microbiota have been shown to be associated with important cognitive developmental effects, and 3) helminth infections have been shown to alter the gut microbiota structure. Evidence on the complex interactions between extrinsic (parasite) and intrinsic (host-derived) factors has been synthesised and discussed. While evidence in favour of the helminth-gut microbiota-central nervous system hypothesis is circumstantial, it would be unwise to rule it out as a possible mechanism by which gastrointestinal helminth infections induce childhood cognitive morbidity. Further empirical studies are necessary to test an indirect effect of helminth infections on the modulation of mood and behaviour through its effects on the gut microbiota.
Assuntos
Encéfalo , Desenvolvimento Infantil , Disfunção Cognitiva/psicologia , Disbiose/psicologia , Microbioma Gastrointestinal , Helmintíase/psicologia , Enteropatias Parasitárias/psicologia , Adolescente , Sistema Nervoso Central , Criança , Cognição , Disfunção Cognitiva/microbiologia , Disfunção Cognitiva/parasitologia , Disbiose/microbiologia , Disbiose/parasitologia , Helmintíase/microbiologia , Humanos , Enteropatias Parasitárias/microbiologiaRESUMO
Helminth infections and nutrition can independently alter the composition and abundance of the gastrointestinal microbiota, however, their combined effect is poorly understood. Here, we used the T. retortaeformis-rabbit system to examine how the helminth infection and host restriction from coprophagy/ready-to-absorb nutrients affected the duodenal microbiota, and how these changes related to the acquired immune response at the site of infection. A factorial experiment was performed where the bacterial community, its functionality and the immune response were examined in four treatments (Infect, Infect+Collar, Control+Collar and Control). Helminths reduced the diversity and abundance of the microbiota while the combination of parasites and coprophagic restriction led to a more diversified and abundant microbiota than infected cases, without significantly affecting the intensity of infection. Animals restricted from coprophagy and free from parasites exhibited the richest and most abundant bacterial community. By forcing the individuals to absorb nutrients from less digested food, the coprophagic restriction appears to have facilitated the diversity and proliferation of bacteria in the duodenum. Changes in the microbiota were more clearly associated with changes in the immune response for the infected than the nutrient restricted animals. The functional and metabolic characteristics of the duodenal microbiota were not significantly different between treatments. Overall, infection and diet affect the gut microbiota but their interactions and outcome can be complex. These findings can have important implications for the development of control measures to helminth infections where poor nutrition/malnutrition can also be a concern.
Assuntos
Microbioma Gastrointestinal/genética , Helmintíase/microbiologia , Imunidade Inata/genética , Microbiota/genética , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Coprofagia , Digestão/genética , Ingestão de Alimentos/genética , Helmintíase/genética , Helmintíase/metabolismo , Helmintos/patogenicidade , Interações Hospedeiro-Patógeno/genética , Humanos , Intestino Delgado/microbiologia , CoelhosRESUMO
The intestinal microbiota undergoes active remodeling in the first 6 to 18 months of life, during which time the characteristics of the adult microbiota are developed. This process is strongly influenced by the early diet and enteric pathogens. Enteric infections and malnutrition early in life may favor microbiota dysbiosis and small intestinal bacterial overgrowth, resulting in intestinal barrier dysfunction and translocation of intestinal bacterial products, ultimately leading to low-grade, chronic, subclinical systemic inflammation. The leaky gut-derived low-grade systemic inflammation may have profound consequences on the gut-liver-brain axis, compromising normal growth, metabolism, and cognitive development. This review examines recent data suggesting that early-life enteric infections that lead to intestinal barrier disruption may shift the intestinal microbiota toward chronic systemic inflammation and subsequent impaired cognitive development.