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

2021 ◽  
Author(s):  
Klara M Wanelik ◽  
Mike Begon ◽  
Janette E Bradley ◽  
Ida M Friberg ◽  
Christopher H Taylor ◽  
...  

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.

2016 ◽  
Vol 283 (1841) ◽  
pp. 20161760 ◽  
Author(s):  
Mathieu Douhard ◽  
Leif Egil Loe ◽  
Audun Stien ◽  
Christophe Bonenfant ◽  
R. Justin Irvine ◽  
...  

The internal predictive adaptive response (internal PAR) hypothesis predicts that individuals born in poor conditions should start to reproduce earlier if they are likely to have reduced performance in later life. However, whether this is the case remains unexplored in wild populations. Here, we use longitudinal data from a long-term study of Svalbard reindeer to examine age-related changes in adult female life-history responses to environmental conditions experienced in utero as indexed by rain-on-snow (ROS utero ). We show that females experiencing high ROS utero had reduced reproductive success only from 7 years of age, independent of early reproduction. These individuals were able to maintain the same annual reproductive success between 2 and 6 years as phenotypically superior conspecifics that experienced low ROS utero . Young females born after high ROS utero engage in reproductive events at lower body mass (about 2.5 kg less) than those born after low ROS utero . The mean fitness of females that experienced poor environmental conditions in early life was comparable with that of females exposed to good environmental conditions in early life. These results are consistent with the idea of internal PAR and suggest that the life-history responses to early-life conditions can buffer the delayed effects of weather on population dynamics.


2017 ◽  
Vol 70 (3) ◽  
pp. 179-183 ◽  
Author(s):  
Sophie E. Moore

Background: Exposures during early life are increasingly being recognised as factors that play an important role in the aetiology of chronic non-communicable diseases (NCDs). The “Developmental Origins of Health and Disease” (DOHaD) hypothesis asserts that adverse early-life exposures - most notably unbalanced nutrition - leads to an increased risk for a range of NCDs and that disease risk is highest when there is a “mismatch” between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in settings undergoing a rapid nutrition transition. Summary: We investigated the link between early-life nutritional exposures and long-term health in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomised controlled trials of nutritional supplementation in pregnancy, and the “experiment of nature” that seasonality in this region provides, we investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs. Key Messages: Our work in rural Gambia suggests that in populations with high rates of under-nutrition in early life, the immune system may be sensitive to nutritional deficiencies early in life, resulting in a greater susceptibility to infection-related morbidity and mortality.


2010 ◽  
Vol 1 (4) ◽  
pp. 367-382 ◽  
Author(s):  
R. Martin ◽  
A. Nauta ◽  
K. Ben Amor ◽  
L. Knippels ◽  
J. Knol ◽  
...  

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.


2016 ◽  
Vol 113 (32) ◽  
pp. 8951-8956 ◽  
Author(s):  
Adam D. Hayward ◽  
Francesca L. Rigby ◽  
Virpi Lummaa

A leading hypothesis proposes that increased human life span since 1850 has resulted from decreased exposure to childhood infections, which has reduced chronic inflammation and later-life mortality rates, particularly from cardiovascular disease, stroke, and cancer. Early-life cohort mortality rate often predicts later-life survival in humans, but such associations could arise from factors other than disease exposure. Additionally, the impact of early-life disease exposure on reproduction remains unknown, and thus previous work ignores a major component of fitness through which selection acts upon life-history strategy. We collected data from seven 18th- and 19th-century Finnish populations experiencing naturally varying mortality and fertility levels. We quantified early-life disease exposure as the detrended child mortality rate from infectious diseases during an individual’s first 5 y, controlling for important social factors. We found no support for an association between early-life disease exposure and all-cause mortality risk after age 15 or 50. We also found no link between early-life disease exposure and probability of death specifically from cardiovascular disease, stroke, or cancer. Independent of survival, there was no evidence to support associations between early-life disease exposure and any of several aspects of reproductive performance, including lifetime reproductive success and age at first birth, in either males or females. Our results do not support the prevailing assertion that exposure to infectious diseases in early life has long-lasting associations with later-life all-cause mortality risk or mortality putatively linked to chronic inflammation. Variation in adulthood conditions could therefore be the most likely source of recent increases in adult life span.


2011 ◽  
Vol 5 ◽  
pp. JEN.S6530 ◽  
Author(s):  
Liisa A. Tremere

The GABA-A receptor has been strongly implicated in the organization and function of cortical sensory circuits in the adult mammal. In the present work, changes in the expression patterns of select GABA-A subunits were examined as a function of development. The RNA expression profiles for three subunit types were studied, α1, β2/3 and δ at four developmental time points, (p0, p15, p30 and p90). The o1, β2/3 subunits were present at birth and following a modest increase early in life; mRNA expression for these subunits were found at stable levels throughout life. The expression pattern for the δ subunit showed the most dramatic changes in the number of positive cells as a function of age. In early life, p0 through p15 expression of mRNA for the δ subunit was quite low but increased in later life, p30 and p90. Together these data suggest that much of the potential for inhibitory connectivity is laid down in the pre and early post-natal periods.


2015 ◽  
Vol 282 (1804) ◽  
pp. 20143053 ◽  
Author(s):  
Adam D. Hayward ◽  
Ilona Nenko ◽  
Virpi Lummaa

The physiology of reproductive senescence in women is well understood, but the drivers of variation in senescence rates are less so. Evolutionary theory predicts that early-life investment in reproduction should be favoured by selection at the cost of reduced survival and faster reproductive senescence. We tested this hypothesis using data collected from preindustrial Finnish church records. Reproductive success increased up to age 25 and was relatively stable until a decline from age 41. Women with higher early-life fecundity (ELF; producing more children before age 25) subsequently had higher mortality risk, but high ELF was not associated with accelerated senescence in annual breeding success. However, women with higher ELF experienced faster senescence in offspring survival. Despite these apparent costs, ELF was under positive selection: individuals with higher ELF had higher lifetime reproductive success. These results are consistent with previous observations in both humans and wild vertebrates that more births and earlier onset of reproduction are associated with reduced survival, and with evolutionary theory predicting trade-offs between early reproduction and later-life survival. The results are particularly significant given recent increases in maternal ages in many societies and the potential consequences for offspring health and fitness.


2021 ◽  
pp. 002214652110054
Author(s):  
Sarah A. Mustillo ◽  
Miao Li ◽  
Patricia Morton ◽  
Kenneth F. Ferraro

Prior research reveals that negative early-life experiences play a major role in the development of obesity in later life, but few studies identify mechanisms that alter the lifetime risk of obesity. This study examines the influence of negative childhood experiences on body mass index (BMI) and obesity (BMI ≥30) during older adulthood and the psychosocial and behavioral pathways involved. Using a nationally representative sample, we examine the influence of cumulative misfortune as well as five separate domains of misfortune on BMI and obesity. Results show that four of the five domains are associated with BMI and obesity either directly, indirectly, or both. The influence of cumulative misfortune on the outcomes is mediated by three adult factors: socioeconomic status, depressive symptoms, and physical activity. The mediators identified here provide targets for intervention among older adults to help offset the health risks of excess BMI attributable of early-life exposure to misfortune.


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Jan K. Nowak ◽  
Marzena Dworacka ◽  
Nazgul Gubaj ◽  
Arystan Dossimov ◽  
Zhumabek Dossimov ◽  
...  

Abstract Background The expression profiles of the intestinal mucosa have not been comprehensively investigated in asthma. We aimed to explore this in the Correlated Expression and Disease Association Research (CEDAR) patient cohort. Methods Differential expression analysis of ileal, transverse colon, and rectal biopsies were supplemented by a comparison of transcriptomes from platelets and leukocytes subsets, including CD4+, CD8+, CD14+, CD15+, and CD19+ cells. Asthma patients (n = 15) and controls (n = 15) had similar age (p = 0.967), body mass index (p = 0.870), similar numbers of females (80%) and smoking rates (13.3%). Results Significant differential expression was found in the ileum alone, and not in any other cell/tissue types. More genes were found to be overexpressed (1,150) than under-expressed (380). The most overexpressed genes included Fc Fragment of IgG Binding Protein (FCGBP, logFC = 3.01, pFDR = 0.015), Mucin 2 (MUC2, logFC = 2.78, pFDR = 0.015), and Alpha 1B Defensin (DEFA1B, logFC = 2.73, pFDR = 0.024). Gene ontology implicated the immune system, including interleukins 4 and 13, as well as antimicrobial peptides in this overexpression. There was concordance of gene over- (STAT1, XBP1) and underexpression (NELF, RARA) in asthma and Crohn’s disease ileum when our results were compared to another dataset (p = 3.66 × 10–7). Conclusion Ileal mucosa in asthma exhibits a specific transcriptomic profile, which includes the overexpression of innate immune genes, mostly characteristic of Paneth and goblet cells, in addition to other changes that may resemble Crohn’s disease.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2412
Author(s):  
Sonia González ◽  
Marta Selma-Royo ◽  
Silvia Arboleya ◽  
Cecilia Martínez-Costa ◽  
Gonzalo Solís ◽  
...  

The early life gut microbiota has been reported to be involved in neonatal weight gain and later infant growth. Therefore, this early microbiota may constitute a target for the promotion of healthy neonatal growth and development with potential consequences for later life. Unfortunately, we are still far from understanding the association between neonatal microbiota and weight gain and growth. In this context, we evaluated the relationship between early microbiota and weight in a cohort of full-term infants. The absolute levels of specific fecal microorganisms were determined in 88 vaginally delivered and 36 C-section-delivered full-term newborns at 1 month of age and their growth up to 12 months of age. We observed statistically significant associations between the levels of some early life gut microbes and infant weight gain during the first year of life. Classifying the infants into tertiles according to their Staphylococcus levels at 1 month of age allowed us to observe a significantly lower weight at 12 months of life in the C-section-delivered infants from the highest tertile. Univariate and multivariate models pointed out associations between the levels of some fecal microorganisms at 1 month of age and weight gain at 6 and 12 months. Interestingly, these associations were different in vaginally and C-section-delivered babies. A significant direct association between Staphylococcus and weight gain at 1 month of life was observed in vaginally delivered babies, whereas in C-section-delivered infants, lower Bacteroides levels at 1 month were associated with higher later weight gain (at 6 and 12 months). Our results indicate an association between the gut microbiota and weight gain in early life and highlight potential microbial predictors for later weight gain.


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