Early life: gut microbiota and immune development in infancy

The immune system of infants is actively downregulated during pregnancy and therefore the first months of life represent a period of heightened susceptibility to infection. After birth, there is an age-dependent maturation of the immune system. Exposure to environmental microbial components is suggested to play an important role in the maturation process. The gastrointestinal tract is the major site of interaction between the host immune system and microorganisms, both commensal as well as potentially pathogenic. It is well established that the mammalian immune system is designed to help protect the host from invading microorganisms and other danger signals. However, recent research is emerging in the field of host-microbe interactions showing that commensal microorganisms (microbiota) are most likely one of the drivers of immune development and, in turn the immune system shapes the composition of the microbiota. Specific early microbial exposure of the gut is thought to dramatically reduce the incidence of inflammatory, autoimmune and atopic diseases further fuelling the scientific view that microbial colonisation plays an important role in regulating and fine-tuning the immune system throughout life. Therefore, the use of pre-, pro- and synbiotics may result in a beneficial microbiota composition that might have a pivotal role on the prevention of several important diseases that develop in early life such as necrotizing enterocolitis and atopic eczema.

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Expression of heat shock proteins 27 and 72 correlates with specific commensal microbes in different regions of porcine gastrointestinal tract

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00299.2013 ◽

2014 ◽

Vol 306 (12) ◽

pp. G1033-G1041 ◽

Cited By ~ 17

Author(s):

Hao-Yu Liu ◽

Johan Dicksved ◽

Torbjörn Lundh ◽

Jan Erik Lindberg

Keyword(s):

Immune System ◽

Heat Shock ◽

Heat Shock Proteins ◽

Bacterial Species ◽

Host Immune System ◽

Gi Tract ◽

Microbe Interactions ◽

Cell Type Specific ◽

Host Microbe Interactions ◽

Shock Proteins

The gastrointestinal (GI) tract of mammals is inhabited by trillions of microorganisms, resulting in exceedingly complex networking. The interaction between distinct bacterial species and the host immune system is essential in maintaining homeostasis in the gut ecosystem. For instance, the gut commensal microbiota dictates intestinal mucosa maturation and its abundant immune components, such as cytoprotective heat shock proteins (HSP). Here we examined physiological expression of HSP in the normal porcine GI tract and found it to be gut region- and cell type-specific in response to dietary components, microbes, and microbial metabolites to which the mucosa surface is exposed. Correlations between HSP72 expression and ileal Lactobacillus spp. and colonic clostridia species, and between HSP27 expression and uronic acid ingestion, were important interplays identified here. Thus this study provides novel insights into host-microbe interactions shaping the immune system that are modifiable by dietary regime.

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Glycans in Virus-Host Interactions: A Structural Perspective

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.666756 ◽

2021 ◽

Vol 8 ◽

Author(s):

Nathaniel L. Miller ◽

Thomas Clark ◽

Rahul Raman ◽

Ram Sasisekharan

Keyword(s):

Immune System ◽

Host Cells ◽

Host Immune System ◽

Host Interactions ◽

Viral Glycoproteins ◽

Microbe Interactions ◽

Host Microbe Interactions ◽

Anti Hiv ◽

Structural Perspective

Many interactions between microbes and their hosts are driven or influenced by glycans, whose heterogeneous and difficult to characterize structures have led to an underappreciation of their role in these interactions compared to protein-based interactions. Glycans decorate microbe glycoproteins to enhance attachment and fusion to host cells, provide stability, and evade the host immune system. Yet, the host immune system may also target these glycans as glycoepitopes. In this review, we provide a structural perspective on the role of glycans in host-microbe interactions, focusing primarily on viral glycoproteins and their interactions with host adaptive immunity. In particular, we discuss a class of topological glycoepitopes and their interactions with topological mAbs, using the anti-HIV mAb 2G12 as the archetypical example. We further offer our view that structure-based glycan targeting strategies are ready for application to viruses beyond HIV, and present our perspective on future development in this area.

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Gut mélange à trois: fluctuating selection modulated by microbiota, host immune system, and antibiotics

10.1101/2021.12.30.474527 ◽

2021 ◽

Author(s):

Hugo Condessa Barreto ◽

Beatriz Abreu ◽

Isabel Gordo

Keyword(s):

Immune System ◽

Iron Homeostasis ◽

Host Immune System ◽

Iron Availability ◽

Lipocalin 2 ◽

Fluctuating Selection ◽

Microbe Interactions ◽

Host Microbe Interactions

Iron is critical in host-microbe interactions, and its availability is under tight regulation in the mammalian gut. Antibiotics and inflammation are known to perturb iron availability in the gut, which could subsequently alter host-microbe interactions. Here, we show that an adaptive allele of iscR, encoding a major regulator of iron homeostasis of Escherichia coli, is under fluctuating selection in the mouse gut. In vivo competitions in immune-competent, immune-compromised, and germ-free mice reveal that the selective pressure on an iscR mutant E. coli is modulated by the presence of antibiotics, other members of the microbiota, and the immune system. In vitro assays show that iron availability is an important mediator of the iscR allele fitness benefits or costs. We identify Lipocalin-2, a host's innate immune system protein that prevents bacterial iron acquisition, as a major host mechanism underlying fluctuating selection of the iscR allele. Our results provide a remarkable example of strong fluctuating selection acting on bacterial iron regulation in the mammalian gut.

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The role of the immune system in governing host-microbe interactions in the intestine

Nature Immunology ◽

10.1038/ni.2611 ◽

2013 ◽

Vol 14 (7) ◽

pp. 660-667 ◽

Cited By ~ 191

Author(s):

Eric M Brown ◽

Manish Sadarangani ◽

B Brett Finlay

Keyword(s):

Immune System ◽

Microbe Interactions ◽

Host Microbe Interactions

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Gut Microbiota and Mucosal Immunity in the Neonate

Medical Sciences ◽

10.3390/medsci6030056 ◽

2018 ◽

Vol 6 (3) ◽

pp. 56 ◽

Cited By ~ 19

Author(s):

Majda Dzidic ◽

Alba Boix-Amorós ◽

Marta Selma-Royo ◽

Alex Mira ◽

Maria Collado

Keyword(s):

Immune System ◽

Gut Microbiota ◽

System Response ◽

Delivery Mode ◽

Complex Dynamic ◽

Close Relationship ◽

Gut Immunity ◽

Microbe Interactions ◽

Immune System Response ◽

Host Microbe Interactions

Gut microbiota colonization is a complex, dynamic, and step-wise process that is in constant development during the first years of life. This microbial settlement occurs in parallel with the maturation of the immune system, and alterations during this period, due to environmental and host factors, are considered to be potential determinants of health-outcomes later in life. Given that host–microbe interactions are mediated by the immune system response, it is important to understand the close relationship between immunity and the microbiota during birth, lactation, and early infancy. This work summarizes the evidence to date on early gut microbiota colonization, and how it influences the maturation of the infant immune system and health during the first 1000 days of life. This review will also address the influence of perinatal antibiotic intake and the importance of delivery mode and breastfeeding for an appropriate development of gut immunity.

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Stabilization and optimization of host-microbe-environment interactions as a potential reason for the behavior of natal philopatry

Animal Microbiome ◽

10.1186/s42523-021-00087-3 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Ting-bei Bo ◽

Kevin D. Kohl

Keyword(s):

Gut Microbiota ◽

Early Life ◽

Survival Rates ◽

Genetic Optimization ◽

Natal Philopatry ◽

Future Directions ◽

Animal Development ◽

Key Factor ◽

Microbe Interactions ◽

Host Microbe Interactions

AbstractMany animals engage in a behavior known as natal philopatry, where after sexual maturity they return to their own birthplaces for subsequent reproduction. There are many proposed ultimate factors that may underlie the evolution of natal philopatry, such as genetic optimization, suitable living conditions, and friendly neighbors, which can improve the survival rates of offspring. However, here we propose that a key factor that has been overlooked could be the colonization of gut microbiota during early life and the effects these microorganisms have on host performance and fitness. In addition to the bacteria transmitted from the mother to offspring, microbes from the surrounding environment also account for a large proportion of the developing gut microbiome. While it was long believed that microbial species all have global distributions, we now know that there are substantial geographic differences and dispersal limitations to environmental microbes. The establishment of gut microbiota during early life has enormous impacts on animal development, including energy metabolism, training of the immune system, and cognitive development. Moreover, these microbial effects scale to influence animal performance and fitness, raising the possibility for natural selection to act on the integrated combination of gut microbial communities and host genetics (i.e. the holobiont). Therefore, in this paper, we propose a hypothesis: that optimization of host-microbe-environment interactions represents a potentially important yet overlooked reason for natal philopatry. Microbiota obtained by natal philopatry could help animals adapt to the environment and improve the survival rates of their young. We propose future directions to test these ideas, and the implications that this hypothesis has for our understanding of host-microbe interactions.

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Maternal Microbiota, Early Life Colonization and Breast Milk Drive Immune Development in the Newborn

Frontiers in Immunology ◽

10.3389/fimmu.2021.683022 ◽

2021 ◽

Vol 12 ◽

Author(s):

Cristina Kalbermatter ◽

Nerea Fernandez Trigo ◽

Sandro Christensen ◽

Stephanie C. Ganal-Vonarburg

Keyword(s):

Immune System ◽

Breast Milk ◽

Innate Immune System ◽

Early Life ◽

Defense Mechanism ◽

Adaptive Immune System ◽

Innate Immune ◽

Long Term Effects ◽

Immune Development ◽

Dietary Antigens

The innate immune system is the oldest protection strategy that is conserved across all organisms. Although having an unspecific action, it is the first and fastest defense mechanism against pathogens. Development of predominantly the adaptive immune system takes place after birth. However, some key components of the innate immune system evolve during the prenatal period of life, which endows the newborn with the ability to mount an immune response against pathogenic invaders directly after birth. Undoubtedly, the crosstalk between maternal immune cells, antibodies, dietary antigens, and microbial metabolites originating from the maternal microbiota are the key players in preparing the neonate’s immunity to the outer world. Birth represents the biggest substantial environmental change in life, where the newborn leaves the protective amniotic sac and is exposed for the first time to a countless variety of microbes. Colonization of all body surfaces commences, including skin, lung, and gastrointestinal tract, leading to the establishment of the commensal microbiota and the maturation of the newborn immune system, and hence lifelong health. Pregnancy, birth, and the consumption of breast milk shape the immune development in coordination with maternal and newborn microbiota. Discrepancies in these fine-tuned microbiota interactions during each developmental stage can have long-term effects on disease susceptibility, such as metabolic syndrome, childhood asthma, or autoimmune type 1 diabetes. In this review, we will give an overview of the recent studies by discussing the multifaceted emergence of the newborn innate immune development in line with the importance of maternal and early life microbiota exposure and breast milk intake.

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Interplays between human microbiota and microRNAs in COVID-19 pathogenesis: a literature review

Physical Activity and Nutrition ◽

10.20463/pan.2021.0008 ◽

2021 ◽

Vol 25 (2) ◽

pp. 1-7

Author(s):

Bok Sil Hong ◽

Myoung-Ryu Kim

Keyword(s):

Molecular Mechanisms ◽

Host Immune System ◽

Host Gene Expression ◽

Human Microbiota ◽

Inflammatory Status ◽

Bidirectional Association ◽

Comprehensive Picture ◽

Microbe Interactions ◽

Host Microbe Interactions ◽

Gut Microbiota Composition

[Purpose] Recent studies have shown that COVID-19 is often associated with altered gut microbiota composition and reflects disease severity. Furthermore, various reports suggest that the interaction between COVID-19 and host-microbiota homeostasis is mediated through the modulation of microRNAs (miRNAs). Thus, in this review, we aim to summarize the association between human microbiota and miRNAs in COVID-19 pathogenesis.[Methods] We searched for the existing literature using the keywords such “COVID-19 or microbiota,” “microbiota or microRNA,” and “COVID-19 or probiotics” in PubMed until March 31, 2021. Subsequently, we thoroughly reviewed the articles related to microbiota and miRNAs in COVID-19 to generate a comprehensive picture depicting the association between human microbiota and microRNAs in the pathogenesis of COVID-19.[Results] There exists strong experimental evidence suggesting that the composition and diversity of human microbiota are altered in COVID-19 patients, implicating a bidirectional association between the respiratory and gastrointestinal tracts. In addition, SARS-CoV-2 encoded miRNAs and host cellular microRNAs modulated by human microbiota can interfere with viral replication and regulate host gene expression involved in the initiation and progression of COVID-19. These findings suggest that the manipulation of human microbiota with probiotics may play a significant role against SARS-CoV-2 infection by enhancing the host immune system and lowering the inflammatory status.[Conclusion] The human microbiota-miRNA axis can be used as a therapeutic approach for COVID-19. Hence, further studies are needed to investigate the exact molecular mechanisms underlying the regulation of miRNA expression in human microbiota and how these miRNA profiles mediate viral infection through host-microbe interactions.

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Early-life immune expression profiles predict later life health and fitness in a wild rodent

10.1101/2021.10.08.463659 ◽

2021 ◽

Author(s):

Klara M Wanelik ◽

Mike Begon ◽

Janette E Bradley ◽

Ida M Friberg ◽

Christopher H Taylor ◽

...

Keyword(s):

Reproductive Success ◽

Early Life ◽

Expression Profiles ◽

Natural Populations ◽

Later Life ◽

Immune Development ◽

Immune Genes ◽

Susceptibility To Infection ◽

Health And Fitness ◽

Longitudinal Sampling

Individuals differ in the nature of the immune responses they produce, affecting disease susceptibility and ultimately health and fitness. These differences have been hypothesised to have an origin in events experienced early in life that then affect trajectories of immune development and responsiveness. Here we investigate early life influences on immune expression profiles using a natural population of field voles, Microtus agrestis, in which we are able to monitor variation between and within individuals though time by repeat (longitudinal) sampling of individually marked animals. We analysed the co-expression of 20 immune genes in early life to create a correlational network consisting of three main clusters, one of which (containing Gata3, Il10 and Il17) was associated with later life reproductive success and susceptibility to chronic bacterial (Bartonella) infection. More detailed analyses supported associations between early life expression of Il17 and reproductive success later in life, and of increased Il10 expression early in life and later infection with Bartonella. We also found significant association between an Il17 genotype and the early life expression of Il10. Our results demonstrate that immune expression profiles can be manifested during early life with effects that persist through adulthood and that shape the variability among individuals in susceptibility to infection and fitness widely seen in natural populations.

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The Suckling Rat as a Model for Immunonutrition Studies in Early Life

Clinical and Developmental Immunology ◽

10.1155/2012/537310 ◽

2012 ◽

Vol 2012 ◽

pp. 1-16 ◽

Cited By ~ 27

Author(s):

Francisco J. Pérez-Cano ◽

Àngels Franch ◽

Cristina Castellote ◽

Margarida Castell

Keyword(s):

Immune System ◽

Early Life ◽

Current Knowledge ◽

System Development ◽

Maternal Diet ◽

Limited Data ◽

Immune Development ◽

Immune System Development ◽

Experimental Approaches ◽

Immunomodulatory Properties

Diet plays a crucial role in maintaining optimal immune function. Research demonstrates the immunomodulatory properties and mechanisms of particular nutrients; however, these aspects are studied less in early life, when diet may exert an important role in the immune development of the neonate. Besides the limited data from epidemiological and human interventional trials in early life, animal models hold the key to increase the current knowledge about this interaction in this particular period. This paper reports the potential of the suckling rat as a model for immunonutrition studies in early life. In particular, it describes the main changes in the systemic and mucosal immune system development during rat suckling and allows some of these elements to be established as target biomarkers for studying the influence of particular nutrients. Different approaches to evaluate these immune effects, including the manipulation of the maternal diet during gestation and/or lactation or feeding the nutrient directly to the pups, are also described in detail. In summary, this paper provides investigators with useful tools for better designing experimental approaches focused on nutrition in early life for programming and immune development by using the suckling rat as a model.

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