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Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance.

Houlden A, Hayes KS, Bancroft AJ, Worthington JJ, Wang P, Grencis RK, Roberts IS - PLoS ONE (2015)

Bottom Line: Communities were profiled using DGGE, 454 pyrosequencing, and metabolomics.This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides.This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, United Kingdom.

ABSTRACT
Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. Communities were profiled using DGGE, 454 pyrosequencing, and metabolomics. Changes in microbial composition occurred between 14 and 28 days post infection, resulting in significant changes in α and β- diversity. This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides. Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. Following clearance of infection the intestinal microbiota underwent additional changes gradually transitioning by day 91 towards a microbiota of an uninfected animal. These data indicate that the changes in microbiota as a consequence of infection were transitory requiring the presence of the pathogen for maintenance. Interestingly this was not observed for all of the key immune cell populations associated with chronic T. muris infection. This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation.

No MeSH data available.


Related in: MedlinePlus

NMDS analysis of bacterial communities in stool samples assessed by 454 pyrosequencing at individual time-points:Comparisons were made between the groups Naïve, naïve antihelminthic treated, infected antihelminthic treated and Infected, in order of dark blue, light blue, orange, red. a) Day 0 there were no significant differences, b) day 28 & c) day 41, naïve and naïve antihelminthic treated were significantly different to infected and infected antihelminthic treated (p < 0.0083), D91 all significantly different (p < 0.0083). Axis represent scale for Euclidian distance between samples centred on zero, Stress indicates the quality of fit of data (>0.2 is a good fit).
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pone.0125945.g006: NMDS analysis of bacterial communities in stool samples assessed by 454 pyrosequencing at individual time-points:Comparisons were made between the groups Naïve, naïve antihelminthic treated, infected antihelminthic treated and Infected, in order of dark blue, light blue, orange, red. a) Day 0 there were no significant differences, b) day 28 & c) day 41, naïve and naïve antihelminthic treated were significantly different to infected and infected antihelminthic treated (p < 0.0083), D91 all significantly different (p < 0.0083). Axis represent scale for Euclidian distance between samples centred on zero, Stress indicates the quality of fit of data (>0.2 is a good fit).

Mentions: Bacterial Community composition was assessed by NMDS on the community composition on the rarefied OTU table to prevent bias by sequencing depth. This allowed the comparison of the compositional make up of communities to be compared between samples, over time. NMDS analysis demonstrated a clear shift in the microbial communities as a result of T. muris infection from day 28 separating away from the naive communities with the indication of the infected mebendazole treated communities returning towards a naive population by day 91 after clearance of the infection (Fig 6). Each treatment/cage was compared at each time point with Bonferoni correction to p < 0.0083. At day 0 (Fig 6A) the baseline start point, there was no significant differences between samples. At day 28 (Fig 6B) there was clear separation of infected mice from naïve mice, this separation continued at day 41 (Fig 6C) between Naïve treatments and Infected treatments with an increase distance between groups on NMDS. By 91 (Fig 6D) all samples were significantly different to one another. No cage differences were identified within groups at any time points.


Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance.

Houlden A, Hayes KS, Bancroft AJ, Worthington JJ, Wang P, Grencis RK, Roberts IS - PLoS ONE (2015)

NMDS analysis of bacterial communities in stool samples assessed by 454 pyrosequencing at individual time-points:Comparisons were made between the groups Naïve, naïve antihelminthic treated, infected antihelminthic treated and Infected, in order of dark blue, light blue, orange, red. a) Day 0 there were no significant differences, b) day 28 & c) day 41, naïve and naïve antihelminthic treated were significantly different to infected and infected antihelminthic treated (p < 0.0083), D91 all significantly different (p < 0.0083). Axis represent scale for Euclidian distance between samples centred on zero, Stress indicates the quality of fit of data (>0.2 is a good fit).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4418675&req=5

pone.0125945.g006: NMDS analysis of bacterial communities in stool samples assessed by 454 pyrosequencing at individual time-points:Comparisons were made between the groups Naïve, naïve antihelminthic treated, infected antihelminthic treated and Infected, in order of dark blue, light blue, orange, red. a) Day 0 there were no significant differences, b) day 28 & c) day 41, naïve and naïve antihelminthic treated were significantly different to infected and infected antihelminthic treated (p < 0.0083), D91 all significantly different (p < 0.0083). Axis represent scale for Euclidian distance between samples centred on zero, Stress indicates the quality of fit of data (>0.2 is a good fit).
Mentions: Bacterial Community composition was assessed by NMDS on the community composition on the rarefied OTU table to prevent bias by sequencing depth. This allowed the comparison of the compositional make up of communities to be compared between samples, over time. NMDS analysis demonstrated a clear shift in the microbial communities as a result of T. muris infection from day 28 separating away from the naive communities with the indication of the infected mebendazole treated communities returning towards a naive population by day 91 after clearance of the infection (Fig 6). Each treatment/cage was compared at each time point with Bonferoni correction to p < 0.0083. At day 0 (Fig 6A) the baseline start point, there was no significant differences between samples. At day 28 (Fig 6B) there was clear separation of infected mice from naïve mice, this separation continued at day 41 (Fig 6C) between Naïve treatments and Infected treatments with an increase distance between groups on NMDS. By 91 (Fig 6D) all samples were significantly different to one another. No cage differences were identified within groups at any time points.

Bottom Line: Communities were profiled using DGGE, 454 pyrosequencing, and metabolomics.This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides.This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, United Kingdom.

ABSTRACT
Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. Communities were profiled using DGGE, 454 pyrosequencing, and metabolomics. Changes in microbial composition occurred between 14 and 28 days post infection, resulting in significant changes in α and β- diversity. This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides. Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. Following clearance of infection the intestinal microbiota underwent additional changes gradually transitioning by day 91 towards a microbiota of an uninfected animal. These data indicate that the changes in microbiota as a consequence of infection were transitory requiring the presence of the pathogen for maintenance. Interestingly this was not observed for all of the key immune cell populations associated with chronic T. muris infection. This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation.

No MeSH data available.


Related in: MedlinePlus