Effect of maternal probiotic intervention on HPA axis, immunity and gut microbiota in a rat model of irritable bowel syndrome - PubMed (original) (raw)

Effect of maternal probiotic intervention on HPA axis, immunity and gut microbiota in a rat model of irritable bowel syndrome

Javad Barouei et al. PLoS One. 2012.

Abstract

Objective: 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.

Design: 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.

Results: 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.

Conclusion: 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. Effect of maternal probiotic intervention and stress on ACTH levels.

A) Effect of neonatal maternal separation (MS) on natural log transformed plasma ACTH concentrations (LnACTH, least squares means+SE). Initial ACTH data were expressed as pg/mL plasma. The filled bar represents neonatally separated animals (MS, n = 107) and the hollow bar represents non-separated animals (NS, n = 111). B) Effect of maternal probiotic intervention on natural log transformed plasma ACTH concentrations (LnACTH, least squares means+SE). Hollow bar represents animals born to vehicle-treated dams (n = 111). Filled bar represents animals born to probiotic-treated dams (n = 107). C) Effect of adult stress on natural log transformed plasma ACTH concentrations (LnACTH, least squares means+SE). Hollow bar represents animals exposed to no adult stress (NA, n = 71). Filled bar represents animals exposed to adult stress (AS, (n = 72). An asterisk (*) indicates statistical significant difference (_p_≤0.05).

Figure 2

Figure 2. Effect of maternal probiotic intervention on neonatal corticosterone levels.

Effect of maternal probiotic intervention on natural log transformed plasma corticosterone concentrations (LnCort, least squares means+SE) at PND 24. Initial corticosterone data were expressed as ng/mL plasma. The filled bar represents animals born to probiotic-treated dams (n = 40) and the hollow bar represents animals born to vehicle-treated dams (n = 45). An asterisk (*) indicates statistical significant difference (_p_≤0.05).

Figure 3

Figure 3. Effect of maternal probiotics, stress and gender on adult corticosterone levels.

A) Effect of maternal probiotic intervention and sex on natural log (Ln) transformed plasma corticosterone levels (LnCort, least squares means+SE). Initial corticosterone data were expressed as ng/mL plasma. The figure presents aggregated data across test days (PND 24 and 86). Hollow bars represent males: male vehicle (n = 71), male probiotic (n = 53). Filled bars represent females: female vehicle (n = 62), female probiotic (n = 58). B) Effect of maternal probiotic intervention and adult restraint stress on Ln-transformed plasma corticosterone concentrations (LnCort, least squares means+SE) in adulthood (week 12).Hollow bars represent animals exposed to no-stress in adulthood (NA): NA vehicle (n = 39), NA probiotic (n = 35). Filled bars represent animals exposed to stress in adulthood (AS): AS vehicle (n = 39), AS probiotic (n = 36). C) Effect of adult restraint stress and sex on Ln-transformed plasma corticosterone concentrations (LnCort, least squares means+SE) in adulthood (week 12). Hollow bars represent males: NA male (n = 35), AS males (n = 36). Filled bars represent females: NA females (n = 39), AS females (n = 39). An asterisk (*) indicates statistical significant difference (_p_≤0.05).

Figure 4

Figure 4. Effect of maternal probiotic intervention, stress, and gender on plasma IgA levels.

A) Effect of sex on Ln-transformed plasma IgA concentrations (LnPIgA, least squares means+SE) in rats. The figure presents aggregated data across test days (PND 24 and 86). Initial IgA data were expressed as µg/mL plasma. The hollow bar represents males (n = 109) and the filled bar represents females (n = 117). An asterisk (*) indicates statistical significant difference (_p_≤0.05). B) Effect of maternal probiotic intake and neonatal maternal separation (MS) on Ln-transformed plasma IgA concentrations (LnPIgA, least squares means+SE) in rats at PND 24. The hollow bars represent animals exposed to no-MS (NS): NS vehicle (n = 15), NS probiotic (n = 19). The filled bars represent animals exposed to MS: MS vehicle (n = 19), MS probiotic (n = 20). An asterisk (*) indicates statistical significant difference relative to vehicle NS animals (_p_≤0.05). C) Effect of maternal probiotic intake, neonatal maternal separation (MS) and adult restraint stress (AS) on Ln-transformed plasma IgA concentrations (LnPIgA, least squares means+SE) in adult rats. Hollow bars represent no-stress control animals or those exposed to adult stress (AS): control vehicle (n = 21), AS vehicle (n = 20), control probiotic (n = 17), AS probiotic (n = 17). Filled bars represent MS or MS+AS animals: MS vehicle (n = 20), MS+AS vehicle (n = 20), MS probiotic (n = 18), MS+AS probiotic (n = 19). An asterisk (*) shows significant difference compared to control animals in the vehicle subset (_p_≤0.05).

Figure 5

Figure 5. Maternal probiotic intervention and luminal IgA levels.

Effect of maternal probiotic intervention on Ln-transformed faecal IgA concentrations (LnFIgA, least squares means+SE). Initial IgA data were expressed as µg/gr faeces. The figure presents aggregated data across test days (PND 24 and 86).The filled bar represents animals born to probiotic-treated dams (n = 101) and the hollow bar represents animals born to vehicle-treated dams (n = 113). An asterisk (*) indicates statistical significant difference (_p_≤0.05).

Figure 6

Figure 6. Effect of early life stress and maternal probiotic intake on neonatal gut microflora.

Effect of neonatal maternal separation (MS) and maternal probiotic intake on composition of gut microflora (Log CFU/gr, least squares means+SE) in Wistar rats at PND 24. Hollow bars represent animals exposed to no neonatal stress (NS): NS vehicle (n = 14–20), NS probiotic (n = 19–20). Filled bars represent animals exposed to neonatal maternal separation (MS): MS vehicle (n = 19–20), MS probiotic (n = 20). An asterisk (*) shows significant difference compared to NS animals in the vehicle subset (_p_≤0.05).

Figure 7

Figure 7. Effect of adult stress on faecal counts of aerobic bacteria and Bacteroides.

Effect of exposure to stress in adulthood (week 12) on faecal counts of aerobic bacteria and Bacteroides (Log CFU/gr, least squares means+SE). The hollow bars represent animals exposed to no adult stress (NA): Aerobes NA (n = 72), Bacteroides NA (n = 67). The filled bars represent animals exposed to adult stress (AS): Aerobes AS (n = 75), Bacteroides AS (n = 75). An asterisk (*) indicates statistical significant difference (_p_≤0.05).

Figure 8

Figure 8. Effect of maternal probiotic intake and stress on adult gut microflora.

Effect of maternal probiotic intake, neonatal maternal separation (MS) and adult restraint stress (AS) on faecal counts of anaerobes, enterococci and clostridia (Log CFU/gr, least squares means+SE) in Wistar rats at week 12. Hollow bars represent no-stress control animals or those exposed to adult stress (AS): control vehicle (n = 11–19), AS vehicle (n = 18–20), control probiotic (n = 17), AS probiotic (n = 17). Filled bars represent MS or MS+AS animals: MS vehicle (n = 20), MS+AS vehicle (n = 20), MS probiotic (n = 18), MS+AS probiotic (n = 19). An asterisk (*) shows significant difference compared to non-stressed (NS-NA) animals in the vehicle subset (_p_≤0.05).

Figure 9

Figure 9. Effect of maternal probiotic intake and adult stress on bifidobacteria.

Effect of maternal probiotic intake and adult restraint stress (AS) on faecal counts of bifidobacteria (Log CFU/gr, least squares means+SE) in Wistar rats at week 12. Hollow bars represent animals exposed to no adult stress (NA): NA vehicle (n = 33), NA probiotic (n = 35). Filled bars represent animals exposed to adult stress (AS): AS vehicle (n = 39), AS probiotic (n = 36). An asterisk (*) shows significant difference compared to non-stressed (NA) animals in the vehicle subset (_p_≤0.05).

Figure 10

Figure 10. Effect of maternal probiotic intake, stress and gender on faecal counts of E. coli.

A) Effect of sex on faecal counts of E. coli (Log CFU/gr, least squares means+SE) in rats. The figure presents aggregated data across test days (PND 24 and 86).The hollow bar represents males (M, n = 109) and the filled bar represents females (F, n = 112). An asterisk (*) indicates statistical significant difference (_p_≤0.05). B) Effect of maternal probiotic intake and neonatal maternal separation (MS) on faecal counts of E. coli (Log CFU/gr, least squares means+SE). The figure presents aggregated data across test days (PND 24 and 86).The hollow bars represent animals exposed to no-MS (NS): NS vehicle (n = 52), NS probiotic (n = 51). The filled bars represent animals exposed to MS: MS vehicle (n = 60), MS probiotic (n = 56). An asterisk (*) indicates statistical significant difference relative to vehicle NNS animals (p≤0.05). C) Effect of MS and AS on faecal counts of E. coli (Log CFU/gr, least squares means+SE) in adult Wistar rats (week 12). The hollow bars represent no-stress control animals or those exposed to AS: control (n = 33), AS (n = 37). The filled bars represent animals exposed to MS or MS+AS: MS (n = 38), MS+AS (n = 39). An asterisk (*) indicates statistical significant difference compared to the control (_p_≤0.05). D) Effect of maternal probiotic intake and AS on faecal counts of E. coli (Log CFU/gr, least squares means+SE) in adult Wistar rats (week 12). The hollow bars represent animals exposed to no-AS (NA): NA vehicle (n = 38), NA probiotic (n = 33). The filled bars represent animals exposed to AS: AS vehicle (n = 40), AS probiotic (n = 36). An asterisk (*) indicates statistical significant difference relative to vehicle NAS animals (_p_≤0.05).

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This work was partly funded by a research Grant (Strategic Pilot Research grant, Project No.: 102-1065) from the University of Newcastle, Australia. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study.

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