Pharmacological restoration of gut barrier function in stressed neonates partially reverses long-term alterations associated with maternal separation

Rincel, Marion; Olier, Maı̈wenn; Minni, Amandine; Oliveira, Camille Monchaux de; Matime, Yann; Gaultier, Eric; Grit, Isabelle; Helbling, Jean‐Christophe; Costa, Anna-Maria; Lépinay, Amandine; Moisan, Marie‐Pierre; Layé, Sophie; Ferrier, Laurent; Parnet, Patricia; Théodorou, Vassilia; Darnaudéry, Muriel

doi:10.1007/s00213-019-05252-w

Cited by 26 publications

(19 citation statements)

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“…It has been shown repeatedly that early life stress by maternal separation in rodents produces long-term effects on the gut and its microbiome. [47][48][49][50][51][52] We showed here that adult sMV females had a higher fecal alpha diversity than cMV females pre-conception, during pregnancy and during lactation. We have previously found this tendency in young rats, 6 suggesting that our stress protocol induces an immediate and life-long increase in microbial alpha diversity.…”

Section: Discussionmentioning

confidence: 53%

“…We have previously found this tendency in young rats, 6 suggesting that our stress protocol induces an immediate and life-long increase in microbial alpha diversity. This is surprising, since other studies of early life stress by maternal separation in rodents have reported a decrease in alpha diversity, 21,51 or no effect. 52 In fact, a more diverse microbiome is usually positively associated with health.…”

Section: Discussionmentioning

confidence: 71%

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Antidepressant treatment with fluoxetine during pregnancy and lactation modulates the gut microbiome and metabolome in a rat model relevant to depression

et al. 2020

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Up to 10% of women use selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy and postpartum. Recent evidence suggests that SSRIs are capable of altering the gut microbiota. However, the interaction between maternal depression and SSRI use on bacterial community composition and the availability of microbiota-derived metabolites during pregnancy and lactation is not clear. We studied this using a rat model relevant to depression, where adult females with a genetic vulnerability and stressed as pups show depressive-like behaviors. Throughout pregnancy and lactation, females received the SSRI fluoxetine or vehicle. High-resolution 16S ribosomal RNA marker gene sequencing and targeted metabolomic analysis were used to assess the fecal microbiome and metabolite availability, respectively. Not surprisingly, we found that pregnancy and lactation segregate in terms of fecal microbiome diversity and composition, accompanied by changes in metabolite availability. However, we also showed that fluoxetine treatment altered important features of this transition from pregnancy to lactation most clearly in previously stressed dams, with lower fecal amino acid concentrations. Amino acid concentrations, in turn, correlated negatively with the relative abundance of bacterial taxa such as Prevotella and Bacteroides. Our study demonstrates an important relationship between antidepressant use during the perinatal period and maternal fecal metabolite availability in a rat model relevant to depression, possibly through parallel changes in the gut microbiome. Since microbial metabolites contribute to homeostasis and development, insults to the maternal microbiome by SSRIs might have health consequences for mother and offspring.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 71%

Antidepressant treatment with fluoxetine during pregnancy and lactation modulates the gut microbiome and metabolome in a rat model relevant to depression

et al. 2020

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“… 46 Importantly, in addition to affect the gut microbiome, early-life stress produces a decreased expression of tight junction expression in the gut, 47 , 48 leading to persistent increase gut permeability, 26 , 49 which allows for systemic leakage of bacteria products, such as LPS, 45 proinflammatory cytokines, 50 , 51 and bacterial translocation from the gut. 52 Since LPS, inflammatory cytokines and bacteria act directly on nociceptors to decrease nociceptive threshold and increase neuronal excitability, 53 – 58 since early-life stress-induced increased gut permeability persists in to adulthood, 59 leakage of LPS, cytokines and/or bacteria could contribute to hyperalgesia seen in adult NLB rats. While NLB-induced stress increase in gut permeability could affect the pharmacokinetics of the poorly absorbable antibiotics used in this study, rifaximin reverses stress-induced gut permeability to normal, non-stressed levels, 22 , 45 and neomycin also reduces gut permeability.…”

Section: Discussionmentioning

confidence: 99%

A role for gut microbiota in early-life stress-induced widespread muscle pain in the adult rat

2021

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Adult rats that experienced neonatal limited bedding (NLB), a form of early-life stress, experience persistent muscle mechanical hyperalgesia. Since there is a growing recognition that the gut microbiome regulates pain and nociception, and that early-life stress produces a long-lasting impact on the gut microbiome, we tested the hypothesis that persistent muscle hyperalgesia seen in adult NLB rats could be ameliorated by interventions that modify the gut microbiome. Adult NLB rats received probiotics, either Lactobacillus rhamnosus GG (10 billion CFU/150 ml) or De Simone Formulation (DSF) (112.5 billion CFU/150 ml mixture of 8 bacterial species), in their drinking water, or non-absorbable antibiotics, rifaximin or neomycin, admixed with cookie dough, to provide 50 mg/kg. Mechanical nociceptive threshold in the gastrocnemius muscle was evaluated before and at several time points after administration of probiotics or antibiotics. Adult NLB rats fed probiotics L. Rhamnosus or DSF, antibiotics, as well as rats fed non-absorbable antibiotics rifaximin or neomycin, had markedly attenuated muscle mechanical hyperalgesia. We hypothesize that persistent skeletal muscle hyperalgesia produced by NLB stress may be, at least in part, due to a contribution of the gut microbiome, and that modulation of gut microbiome using probiotics or non-absorbable antibiotics, may be novel therapeutic approaches for the treatment of chronic musculoskeletal pain.

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“… Species, Strain Own breeding? * ELA model** Sex Total sample size (ELA + control) Test Phase*** Result Social interaction Bahi (2016) Rats, Wistar yes MS, P1-P11 Males 20 Light ↓ Lukas et al (2011) Rats, Wistar yes MS, P1-P14 Males 20 Light = Rincel et al (2016) Rats, Wistar yes MS, P2-P14 Males 14 Light ↓ Rincel et al (2019) Rats, Wistar yes MS, P2-P14 Males 21/21 Light = / = Zugno et al (2013) Rats, Wistar no MS, P1-P10 Males 12 NS = Mehta and Schmauss (2011) Mice, Balb C yes MS, P2-P15 Males 16 Light ...…”

Section: Rodent Behavioral Tests In Cid: Measuring Social Competence mentioning

confidence: 99%

The relevance of a rodent cohort in the Consortium on Individual Development

Veen

Bonapersona

Joëls

2020

Developmental Cognitive Neuroscience

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One of the features of the Consortium on Individual Development is the existence of a rodent cohort, in parallel with the human cohorts. Here we give an overview of the current status. We first elaborate on the choice of rat and mouse models mimicking early life adverse or beneficial conditions during development. We performed a systematic literature search on early life adversity and adult social behavior to address the status quo. Next, we describe the behavioral tasks we used and designed to examine behavioral control and social competence in rodents. The results so far indicate that manipulation of the environment in the first postnatal week only subtly affects social behavior. Stronger effects were seen in the model that targeted early adolescence; once adult, these rats are characterized by increased attention, a higher degree of impulsiveness and reduced social interest in peers. Many experiments in our rodent models with tightly controlled conditions were inspired by findings in human cohorts, and now allow in-depth mechanistic investigations. Vice versa, some of the findings in rodents are currently followed up by dedicated investigations in the human cohorts. This exemplifies the added value of animal investigations in a consortium encompassing primarily human developmental cohorts.

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Pharmacological restoration of gut barrier function in stressed neonates partially reverses long-term alterations associated with maternal separation

Cited by 26 publications

References 68 publications

Antidepressant treatment with fluoxetine during pregnancy and lactation modulates the gut microbiome and metabolome in a rat model relevant to depression

Antidepressant treatment with fluoxetine during pregnancy and lactation modulates the gut microbiome and metabolome in a rat model relevant to depression

A role for gut microbiota in early-life stress-induced widespread muscle pain in the adult rat

The relevance of a rodent cohort in the Consortium on Individual Development

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