The maternal microbiota drives early postnatal innate immune development

Agüero, Mercedes Gomez de; Ganal‐Vonarburg, Stephanie C.; Fuhrer, Tobias; Rupp, Sandra; Uchimura, Yasuhiro; Li, Hai; Steinert, Anna; Heikenwälder, Mathias; Hapfelmeier, Siegfried; Sauer, Uwe; McCoy, Kathy D.; Macpherson, Andrew J.

doi:10.1126/science.aad2571

Cited by 966 publications

(829 citation statements)

References 54 publications

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“…In addition, recent studies have shown that maternal antibodies alter postnatal immunity by increasing aryl hydrocarbon receptors for maternal bacterial metabolites. 144 Additional study is needed into the role of steroidogenesis and gut epithelium function in the developing fetus.…”

Section: Discussionmentioning

confidence: 99%

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

et al. 2018

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Background: Conditions of excess androgen in women, such as polycystic ovary syndrome (PCOS), often exhibit intergenerational transmission. One way in which the risk for PCOS may be increased in daughters of affected women is through exposure to elevated androgens in utero. Hyperandrogenemic conditions have serious health consequences, including increased risk for hypertension and cardiovascular disease. Recently, gut dysbiosis has been found to induce hypertension in rats, such that blood pressure can be normalized through fecal microbial transplant. Therefore, we hypothesized that the hypertension seen in PCOS has early origins in gut dysbiosis caused by in utero exposure to excess androgen. We investigated this hypothesis with a model of prenatal androgen (PNA) exposure and maternal hyperandrogenemia by single-injection of testosterone cypionate or sesame oil vehicle (VEH) to pregnant dams in late gestation. We then completed a gut microbiota and cardiometabolic profile of the adult female offspring. Results: The metabolic assessment revealed that adult PNA rats had increased body weight and increased mRNA expression of adipokines: adipocyte binding protein 2, adiponectin, and leptin in inguinal white adipose tissue. Radiotelemetry analysis revealed hypertension with decreased heart rate in PNA animals. The fecal microbiota profile of PNA animals contained higher relative abundance of bacteria associated with steroid hormone synthesis, Nocardiaceae and Clostridiaceae, and lower abundance of Akkermansia, Bacteroides, Lactobacillus, Clostridium. The PNA animals also had an increased relative abundance of bacteria associated with biosynthesis and elongation of unsaturated short chain fatty acids (SCFAs). Conclusions: We found that prenatal exposure to excess androgen negatively impacted cardiovascular function by increasing systolic and diastolic blood pressure and decreasing heart rate. Prenatal androgen was also associated with gut microbial dysbiosis and altered abundance of bacteria involved in metabolite production of short chain fatty acids. These results suggest that early-life exposure to hyperandrogenemia in daughters of women with PCOS may lead to long-term alterations in gut microbiota and cardiometabolic function.

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Section: Discussionmentioning

confidence: 99%

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

et al. 2018

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“…Interestingly, recent evidence using GF animals also points to a role for the maternal microbiota in influencing early postnatal innate immune development in the infant. In this study monocolonization of GF animals with Escherichia coli HA107 during pregnancy altered the numbers of early postnatal intestinal innate leukocytes and increased small intestinal innate lymphoid cell (ILC) proportions and total numbers compared with GF controls, particularly the NKp46 + RORγt + ILC3 subset (Gomez de Aguero et al, 2016).…”

Section: Microbes and Immunitymentioning

confidence: 90%

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

Dinan

Cryan

2016

Neuropsychopharmacol

201

121

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There is now a large volume of evidence to support the view that the immune system is a key communication pathway between the gut and brain, which plays an important role in stress-related psychopathologies and thus provides a potentially fruitful target for psychotropic intervention. The gut microbiota is a complex ecosystem with a diverse range of organisms and a sophisticated genomic structure. Bacteria within the gut are estimated to weigh in excess of 1 kg in the adult human and the microbes within not only produce antimicrobial peptides, short chain fatty acids, and vitamins, but also most of the common neurotransmitters found in the human brain. That the microbial content of the gut plays a key role in immune development is now beyond doubt. Early disruption of the host-microbe interplay can have lifelong consequences, not just in terms of intestinal function but in distal organs including the brain. It is clear that the immune system and nervous system are in continuous communication in order to maintain a state of homeostasis. Significant gaps in knowledge remain about the effect of the gut microbiota in coordinating the immune-nervous systems dialogue. However, studies using germ-free animals, infective models, prebiotics, probiotics, and antibiotics have increased our understanding of the interplay. Early life stress can have a lifelong impact on the microbial content of the intestine and permanently alter immune functioning. That early life stress can also impact adult psychopathology has long been appreciated in psychiatry. The challenge now is to fully decipher the molecular mechanisms that link the gut microbiota, immune, and central nervous systems in a network of communication that impacts behavior patterns and psychopathology, to eventually translate these findings to the human situation both in health and disease. Even at this juncture, there is evidence to pinpoint key sites of communication where gut microbial interventions either with drugs or diet or perhaps fecal microbiota transplantation may positively impact mental health.

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“…Such influences may be effected through factors including microbial molecular transfer mediated by maternal immunoglobulins transmitted both trans-placentally and through lactation. 48 Defining the interrelated processes of human immune development and microbial acquisition may have a significant impact on our understanding of the pathogenesis of IBD.…”

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confidence: 99%

The gut microbiota of siblings offers insights into microbial pathogenesis of inflammatory bowel disease

et al. 2017

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Siblings of patients with Crohn's disease (CD) have elevated risk of developing CD and display aspects of disease phenotype, including faecal dysbiosis. In our recent article we have used 16S rRNA gene targeted high-throughput sequencing to comprehensively characterize the mucosal microbiota in healthy siblings of CD patients, and determine the influence of genotypic and phenotypic factors on the gut microbiota (dysbiosis). We have demonstrated that the core microbiota of both patients with CD and healthy siblings is significantly less diverse than controls. Faecalibacterium prausnitzii contributed most to core metacommunity dissimilarity between both patients and controls and between siblings and controls. Phenotype/genotype markers of CD risk significantly influenced microbiota variation between and within groups, of which genotype had the largest effect. Individuals with elevated CD-risk display mucosal dysbiosis characterized by reduced diversity of core microbiota and lower abundance of F. prausnitzii. The presence of this dysbiosis in healthy people at-risk of CD implicates microbiological processes in CD pathogenesis.

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The maternal microbiota drives early postnatal innate immune development

Cited by 966 publications

References 54 publications

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

The gut microbiota of siblings offers insights into microbial pathogenesis of inflammatory bowel disease

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