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Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians.

Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, Nikkïla J, Monti D, Satokari R, Franceschi C, Brigidi P, De Vos W - PLoS ONE (2010)

Bottom Line: The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers.This may be explained by a remodelling of the centenarians' microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties.Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, University of Bologna, Bologna, Italy. elena.biagi@unibo.it

ABSTRACT

Background: Age-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections.

Methodology/principal findings: By using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians' microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians.

Conclusions/significance: We provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host's immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.

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Related in: MedlinePlus

Correlation between microbiota composition and plasma levels of pro-inflammatory cytokines.In the RDA blood cytokine levels (red arrows) and age groups (C, S, and Y, red triangles) are used as linear and nominal environmental variables, respectively. Samples belonging to C, S and Y groups are indicated by green circles, blue squares and yellow diamonds, respectively. Responding bacterial subgroups that explained more than 20% of the variability of the samples are indicated by black arrows. First and second ordination axes are plotted, showing 5.8% and 3.1% of the variability in the dataset, respectively. Red arrows which are not labelled corresponds to (clockwise, starting from the left) TNF-α, IFN-γ, IL-2, IL-1α, IL-12p70, and IL-1β. Log transformed data were used for this analysis. Bottom-left, P value obtained by MCPP is reported. Top-left, average blood levels of IL-6 and IL-8 in groups C, S and Y are reported.
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pone-0010667-g004: Correlation between microbiota composition and plasma levels of pro-inflammatory cytokines.In the RDA blood cytokine levels (red arrows) and age groups (C, S, and Y, red triangles) are used as linear and nominal environmental variables, respectively. Samples belonging to C, S and Y groups are indicated by green circles, blue squares and yellow diamonds, respectively. Responding bacterial subgroups that explained more than 20% of the variability of the samples are indicated by black arrows. First and second ordination axes are plotted, showing 5.8% and 3.1% of the variability in the dataset, respectively. Red arrows which are not labelled corresponds to (clockwise, starting from the left) TNF-α, IFN-γ, IL-2, IL-1α, IL-12p70, and IL-1β. Log transformed data were used for this analysis. Bottom-left, P value obtained by MCPP is reported. Top-left, average blood levels of IL-6 and IL-8 in groups C, S and Y are reported.

Mentions: To find possible correlations between the microbiota composition and the cytokines pattern, log-transformed results of pro-inflammatory cytokines quantification and HITChip profiling of the gut microbiota were used in a multivariate analysis, using cytokines plasma levels and the age groups as “environmental variables”. RDA shows that 8.9% of the total variability of the gut microbiota can be related to the pro-inflammatory cytokines pattern (Fig. 4). Relations shown in the plot are statistically significant, as established by MCPP (P = 0.014). In accordance with previous analysis (Fig. 2), the centroid of group C is plotted distant from both the S and Y centroids, highlighting the similarity in the gut microbiota asset and the relation with the inflammatory status between elderly and young adults. Several bacteria belonging to the phylum Proteobacteria seemed to be positively correlated with IL-6 and IL-8. IL-8 was correlated with Alcaligenes faecalis et rel., Leminorella, and Proteus et rel., while IL-6 was correlated with Escherichia coli et rel., Haemophilus, Klebsiella pneumoniae et rel., Pseudomonas, Serratia, Yersinia et rel., and Vibrio. IL-8 and IL-6 were correlated also with Bacillus (Bacilli), Egghertella lenta et rel. (Actinobacteria), and Eubacterium cylindroides et rel. (Clostridium cluster XIVa). On the other side, Eubacterium hallii et rel., Eubacterium ventriosum et rel., Eubacterium rectale et rel., Clostridium nexile et rel., and Outgrouping Clostridium cluster XIVa (all belonging to the Clostridium cluster XIVa) are inversely correlated with IL-6 and IL-8.


Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians.

Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, Nikkïla J, Monti D, Satokari R, Franceschi C, Brigidi P, De Vos W - PLoS ONE (2010)

Correlation between microbiota composition and plasma levels of pro-inflammatory cytokines.In the RDA blood cytokine levels (red arrows) and age groups (C, S, and Y, red triangles) are used as linear and nominal environmental variables, respectively. Samples belonging to C, S and Y groups are indicated by green circles, blue squares and yellow diamonds, respectively. Responding bacterial subgroups that explained more than 20% of the variability of the samples are indicated by black arrows. First and second ordination axes are plotted, showing 5.8% and 3.1% of the variability in the dataset, respectively. Red arrows which are not labelled corresponds to (clockwise, starting from the left) TNF-α, IFN-γ, IL-2, IL-1α, IL-12p70, and IL-1β. Log transformed data were used for this analysis. Bottom-left, P value obtained by MCPP is reported. Top-left, average blood levels of IL-6 and IL-8 in groups C, S and Y are reported.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2871786&req=5

pone-0010667-g004: Correlation between microbiota composition and plasma levels of pro-inflammatory cytokines.In the RDA blood cytokine levels (red arrows) and age groups (C, S, and Y, red triangles) are used as linear and nominal environmental variables, respectively. Samples belonging to C, S and Y groups are indicated by green circles, blue squares and yellow diamonds, respectively. Responding bacterial subgroups that explained more than 20% of the variability of the samples are indicated by black arrows. First and second ordination axes are plotted, showing 5.8% and 3.1% of the variability in the dataset, respectively. Red arrows which are not labelled corresponds to (clockwise, starting from the left) TNF-α, IFN-γ, IL-2, IL-1α, IL-12p70, and IL-1β. Log transformed data were used for this analysis. Bottom-left, P value obtained by MCPP is reported. Top-left, average blood levels of IL-6 and IL-8 in groups C, S and Y are reported.
Mentions: To find possible correlations between the microbiota composition and the cytokines pattern, log-transformed results of pro-inflammatory cytokines quantification and HITChip profiling of the gut microbiota were used in a multivariate analysis, using cytokines plasma levels and the age groups as “environmental variables”. RDA shows that 8.9% of the total variability of the gut microbiota can be related to the pro-inflammatory cytokines pattern (Fig. 4). Relations shown in the plot are statistically significant, as established by MCPP (P = 0.014). In accordance with previous analysis (Fig. 2), the centroid of group C is plotted distant from both the S and Y centroids, highlighting the similarity in the gut microbiota asset and the relation with the inflammatory status between elderly and young adults. Several bacteria belonging to the phylum Proteobacteria seemed to be positively correlated with IL-6 and IL-8. IL-8 was correlated with Alcaligenes faecalis et rel., Leminorella, and Proteus et rel., while IL-6 was correlated with Escherichia coli et rel., Haemophilus, Klebsiella pneumoniae et rel., Pseudomonas, Serratia, Yersinia et rel., and Vibrio. IL-8 and IL-6 were correlated also with Bacillus (Bacilli), Egghertella lenta et rel. (Actinobacteria), and Eubacterium cylindroides et rel. (Clostridium cluster XIVa). On the other side, Eubacterium hallii et rel., Eubacterium ventriosum et rel., Eubacterium rectale et rel., Clostridium nexile et rel., and Outgrouping Clostridium cluster XIVa (all belonging to the Clostridium cluster XIVa) are inversely correlated with IL-6 and IL-8.

Bottom Line: The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers.This may be explained by a remodelling of the centenarians' microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties.Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, University of Bologna, Bologna, Italy. elena.biagi@unibo.it

ABSTRACT

Background: Age-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections.

Methodology/principal findings: By using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians' microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians.

Conclusions/significance: We provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host's immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.

Show MeSH
Related in: MedlinePlus