Nutritional approach to restore impaired intestinal barrier function and growth after neonatal stress in rats
ABSTRACT 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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- "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). "
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 · 3.33 Impact Factor
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ABSTRACT: We previously showed that neonatal maternal separation (MS) of rat pups causes immediate and long-term changes in intestinal physiology. To examine if administration of probiotics affects MS-induced gut dysfunction. MS pups were separated from the dam for 3 h/day from days 4 to 19; non-separated (NS) pups served as controls. Twice per day during the separation period, 10(8) probiotic organisms (two strains of Lactobacillus species) were administered to MS and NS pups; vehicle-treated pups received saline. Studies were conducted on day 20, when blood was collected for corticosterone measurement as an indication of hypothalamus-pituitary-adrenal (HPA) axis activity, and colonic function was studied in tissues mounted in Ussing chambers. Ion transport was indicated by baseline and stimulated short-circuit current (Isc); macromolecular permeability was measured by flux of horseradish peroxidase (HRP) across colonic tissues; and bacterial adherence/penetration into the mucosa was quantified by culturing tissues in selective media. Colonic function and host defence were also evaluated at day 60. Isc and HRP flux were significantly higher in the colon of MS versus NS pups. There was increased adhesion/penetration of total bacteria in MS pups, but a significant reduction in Lactobacillus species. Probiotic administration ameliorated the MS-induced gut functional abnormalities and bacterial adhesion/penetration at both day 20 and 60, and reduced the elevated corticosterone levels at day 20. The results indicate that altered enteric flora are responsible for colonic pathophysiology. Probiotics improve gut dysfunction induced by MS, at least in part by normalisation of HPA axis activity.Gut 12/2007; 56(11):1522-8. DOI:10.1136/gut.2006.117176 · 13.32 Impact Factor
- Gut 12/2007; 56(11):1528, 1556. DOI:10.1136/gut.2006.106559 · 13.32 Impact Factor