Nutritional Approach to Restore Impaired Intestinal Barrier Function and Growth After Neonatal Stress in Rats

Nutrition and Health Department, Nestlé Research Center, Lausanne, Switzerland.
Journal of Pediatric Gastroenterology and Nutrition (Impact Factor: 2.63). 08/2006; 43(1):16-24. DOI: 10.1097/01.mpg.0000226376.95623.9f
Source: PubMed


Psychological stress during the neonatal period results in intestinal barrier dysfunction and growth alterations later in life. We aimed to restore impaired barrier function and growth rate by a nutritional intervention.
Male rat pups (n = 84) were assigned to 1 of 2 rearing conditions from postnatal day (PND) 2 to PND14: S, separated 3 h/d from their mothers, or H, 15 min/d handled controls. From PND15 to PND35, rats received a control diet or a similar diet adapted to contain arachidonic and docosahexaenoic acids, galacto- and fructo-oligosaccharides and Lactobacillus paracasei NCC2461.
Maternal separation had only a minor impact on the measured gut barrier parameters at PND15, whereas it severely affected them at PND35. At this age, intestinal permeability to macromolecules was higher, mucin content in small intestinal tissues was lower and microbiota composition was altered in S compared with H animals. Feeding the adapted diet normalized the intestinal permeability, although it did not restore intestinal mucin content or microbiota. In addition, the adapted diet improved the growth rate recovery of the S animals after weaning and resulted in increased villus length in small intestine.
Our results suggest that an adapted diet containing specific long-chain polyunsaturated fatty acids, prebiotics and probiotics can revert the negative imprinting of neonatal stress on both intestinal barrier function and growth.

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    • "Previous research has shown that MS rats exhibit significantly higher corticosterone levels both in basal conditions and in response to a subsequent stress compared to the control animals [5], [6], [7], [8]. Furthermore, MS resulted in gut dysfunctions such as increased mucosal ion transport [6], [7], [9] and epithelial permeability to macromolecules [6], [7], [8], [9], [10], [11], [12], [13], increased mucosal adherent/penetrated commensal bacteria [6], [7] and bacterial translocation to internal organs [13], decreased intestinal mucin/mucus [12], [14], altered the integrity of gut microbiota [5], [12], [15], increased motility [9], [16] and increased visceral/colonic sensitivity [5], [11], [16], [17], [18], induced intestinal morphological/structural damage and increased mucosal mast cells and goblet cells [11], [13], [14]. "
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    ABSTRACT: To examine whether maternal probiotic intervention influences the alterations in the brain-immune-gut axis induced by neonatal maternal separation (MS) and/or restraint stress in adulthood (AS) in Wistar rats. Dams had free access to drinking water supplemented with Bifidobacterium animalis subsp lactis BB-12® (3×10(9) CFU/mL) and Propionibacterium jensenii 702 (8.0×10(8) CFU/mL) from 10 days before conception until postnatal day (PND) 22 (weaning day), or to control ad lib water. Offspring were subjected to MS from PND 2 to 14 or left undisturbed. From PND 83 to 85, animals underwent 30 min/day AS, or were left undisturbed as controls. On PND 24 and 86, blood samples were collected for corticosterone, ACTH and IgA measurement. Colonic contents were analysed for the composition of microflora and luminal IgA levels. Exposure to MS significantly increased ACTH levels and neonatal fecal counts of aerobic and anaerobic bacteria, E. coli, enterococci and clostridia, but reduced plasma IgA levels compared with non-MS animals. Animals exposed to AS exhibited significantly increased ACTH and corticosterone levels, decreased aerobic bacteria and bifidobacteria, and increased Bacteroides and E. coli counts compared to non-AS animals. MS coupled with AS induced significantly decreased anaerobes and clostridia compared with the non-stress adult controls. Maternal probiotic intervention significantly increased neonatal corticosterone levels which persisted until at least week 12 in females only, and also resulted in elevated adult ACTH levels and altered neonatal microflora comparable to that of MS. However, it improved plasma IgA responses, increased enterococci and clostridia in MS adults, increased luminal IgA levels, and restored anaerobes, bifidobacteria and E. coli to normal in adults. Maternal probiotic intervention induced activation of neonatal stress pathways and an imbalance in gut microflora. Importantly however, it improved the immune environment of stressed animals and protected, in part, against stress-induced disturbances in adult gut microflora.
    PLoS ONE 10/2012; 7(10):e46051. DOI:10.1371/journal.pone.0046051 · 3.23 Impact Factor
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    • "This effect was transient, lasting several days after maternal separation, but the same authors later showed that moderate maternal stress during pregnancy could disrupt infant gut microbiota for six months or longer [105]. Rodent studies support these findings, showing that frequent maternal separation in the first weeks of life is associated with altered gut microbiota in adolescence [106, 107]. New research suggests that it may be possible to mitigate maternal stress-induced effects with prebiotic supplementation during the neonatal period [108]; however, epigenetic mechanisms might also be involved, since rat pups of mothers that exhibited more frequent grooming and licking were found to have differences in DNA methylation, compared to the offspring of less attentive mothers [109]. "
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    ABSTRACT: Perinatal programming, a dominant theory for the origins of cardiovascular disease, proposes that environmental stimuli influence developmental pathways during critical periods of prenatal and postnatal development, inducing permanent changes in metabolism. In this paper, we present evidence for the perinatal programming of asthma via the intestinal microbiome. While epigenetic mechanisms continue to provide new explanations for the programming hypothesis of asthma development, it is increasingly apparent that the intestinal microbiota plays an independent and potentially interactive role. Commensal gut bacteria are essential to immune system development, and exposures disrupting the infant gut microbiota have been linked to asthma. This paper summarizes the recent findings that implicate caesarean delivery, breastfeeding, perinatal stress, probiotics, and antibiotics as modifiers of infant gut microbiota in the development of asthma.
    Clinical and Developmental Immunology 01/2012; 2012(1740-2522):932072. DOI:10.1155/2012/932072 · 2.93 Impact Factor
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    • "Despite the growing interest in brain-gut communication and its possible role in the pathogenesis of stress-related psychiatric disorders such as depression, particularly subtypes with accompany GI symptoms and comorbid IBS, there are few studies dedicated to the search for therapeutic solutions that address both central and peripheral facets of these illnesses. As the maternal separation (MS) model in rodents is considered to be of heuristic value in the study of both brain (Meaney et al., 1996; Levine, 2000; Matthews et al., 2001; Daniels et al., 2004; Matthews and Robbins, 2003; Slotten et al., 2006; Aisa et al., 2007) and GI illnesses (Barreau et al., 2004; Garcia-Rodenas et al., 2006; Welting et al., 2005; Couthino et al., 2002; O'Mahony et al., 2009), it provides a valuable tool to explore the extent of overlap of early life stress effects in the brain and gut, and offers an ideal platform for the assessment of more comprehensive treatments that address both peripheral GI and centrallymediated psychological symptoms. Communication between the brain and the gut can be achieved through the activation of various interrelated systems, including neural pathways of the autonomic nervous system (which involves the vagus nerve and the neurotransmitters noradrenaline (NA) and adrenaline), immune cytokines, or through interactions with hormonal mediators of the HPA axis (reviewed by Forsythe et al., 2010). "
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    ABSTRACT: The concept that intestinal microbial composition not only affects the health of the gut, but also influences centrally-mediated systems involved in mood, is supported by a growing body of literature. Despite the emergent interest in brain-gut communication and its possible role in the pathogenesis of psychiatric disorders such as depression, particularly subtypes with accompanying gastrointestinal (GI) symptoms, there are few studies dedicated to the search for therapeutic solutions that address both central and peripheral facets of these illnesses. This study aims to assess the potential benefits of the probiotic Bifidobacterium infantis in the rat maternal separation (MS) model, a paradigm that has proven to be of value in the study of stress-related GI and mood disorders. MS adult rat offsprings were chronically treated with bifidobacteria or citalopram and subjected to the forced swim test (FST) to assess motivational state. Cytokine concentrations in stimulated whole blood samples, monoamine levels in the brain, and central and peripheral hypothalamic-pituitary-adrenal (HPA) axis measures were also analysed. MS reduced swim behavior and increased immobility in the FST, decreased noradrenaline (NA) content in the brain, and enhanced peripheral interleukin (IL)-6 release and amygdala corticotrophin-releasing factor mRNA levels. Probiotic treatment resulted in normalization of the immune response, reversal of behavioral deficits, and restoration of basal NA concentrations in the brainstem. These findings point to a more influential role for bifidobacteria in neural function, and suggest that probiotics may have broader therapeutic applications than previously considered.
    Neuroscience 11/2010; 170(4):1179-88. DOI:10.1016/j.neuroscience.2010.08.005 · 3.36 Impact Factor
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