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Clinical Trial
. 2015 Apr 14;6(2):e00231-15.
doi: 10.1128/mBio.00231-15.

Functional Dynamics of the Gut Microbiome in Elderly People During Probiotic Consumption

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Free PMC article
Clinical Trial

Functional Dynamics of the Gut Microbiome in Elderly People During Probiotic Consumption

Emiley A Eloe-Fadrosh et al. mBio. .
Free PMC article

Abstract

A mechanistic understanding of the purported health benefits conferred by consumption of probiotic bacteria has been limited by our knowledge of the resident gut microbiota and its interaction with the host. Here, we detail the impact of a single-organism probiotic, Lactobacillus rhamnosus GG ATCC 53103 (LGG), on the structure and functional dynamics (gene expression) of the gut microbiota in a study of 12 healthy individuals, 65 to 80 years old. The analysis revealed that while the overall community composition was stable as assessed by 16S rRNA profiling, the transcriptional response of the gut microbiota was modulated by probiotic treatment. Comparison of transcriptional profiles based on taxonomic composition yielded three distinct transcriptome groups that displayed considerable differences in functional dynamics. The transcriptional profile of LGG in vivo was remarkably concordant across study subjects despite the considerable interindividual nature of the gut microbiota. However, we identified genes involved in flagellar motility, chemotaxis, and adhesion from Bifidobacterium and the dominant butyrate producers Roseburia and Eubacterium whose expression was increased during probiotic consumption, suggesting that LGG may promote interactions between key constituents of the microbiota and the host epithelium. These results provide evidence for the discrete functional effects imparted by a specific single-organism probiotic and challenge the prevailing notion that probiotics substantially modify the resident microbiota within nondiseased individuals in an appreciable fashion.

Importance: Probiotic bacteria have been used for over a century to promote digestive health. Many individuals report that probiotics alleviate a number of digestive issues, yet little evidence links how probiotic microbes influence human health. Here, we show how the resident microbes that inhabit the healthy human gut respond to a probiotic. The well-studied probiotic Lactobacillus rhamnosus GG ATCC 53103 (LGG) was administered in a clinical trial, and a suite of measurements of the resident microbes were taken to evaluate potential changes over the course of probiotic consumption. We found that LGG transiently enriches for functions to potentially promote anti-inflammatory pathways in the resident microbes.

Figures

FIG 1
FIG 1
Community composition, temporal stability, and diversity in the gut microbiota in elderly people. Prevalent bacterial genera identified in the 12 elderly individuals at baseline, on day 28, and on day 56, with relative abundance denoted by circle size. Colors represent phylum affiliations as follows, Actinobacteria (green), Bacteroidetes (red), and Firmicutes (blue). Phylogenetic diversity (PD) is shown for each individual over time and was calculated from the rarefied OTUs. Asterisks denote the genus Ruminococcus classified within two separate families, the Lachnospiraceae (*) and the Ruminococcaceae (**).
FIG 2
FIG 2
RNA-seq transcript phylogeny and dynamics. (A) A correlation matrix was constructed from relative transcript abundances mapped to reference species. The scale bar represents the Pearson correlation coefficient (PCC). A histogram for complete linkage clustering of samples is shown, with transcriptome group designations for the bacterial and archaeal fraction (viral and eukaryotic sequences were removed). (B) Distribution of dominant species (>2% relative abundance) across the three identified transcriptome groups. Species listed in bold were found to be discriminant for pairwise transcriptome group comparisons, with an asterisk denoting discriminant species across all three groups. The inset indicates the Shannon diversity for the three transcriptome groups, where the asterisk denotes significantly different diversity measures as determined by the nonparametric Wilcoxon rank sum test (group 1 versus group 2, P = 0.0031; group 1 versus group 3, P = 0.0031). Clusters of orthologous group (COG) category profiles for each transcriptome group are represented, where the asterisks similarly denote discriminant categories across all three transcriptome groups. COG categories are as follows: RNA processing and modification (category A); chromatin structure and dynamics (B); energy production and conversion (C); cell division, chromosome partitioning (D); amino acid transport and metabolism (E); nucleotide transport and metabolism (F); carbohydrate transport and metabolism (G); coenzyme transport and metabolism (H); lipid transport and metabolism (I); translation and biogenesis (J); transcription (K); replication, recombination, and repair (L); cell wall/membrane/envelope (M); cell motility (N); protein turnover, chaperones (O); inorganic ion transport and metabolism (P); secondary metabolism (Q); general function prediction only (R); function unknown (S); signal transduction mechanisms (T); intracellular trafficking and secretion (U); and defense mechanisms (V).
FIG 3
FIG 3
Global differential expression associated with probiotic consumption. Smear plots represent global KEGG orthologs for comparisons between baseline and day 28 (A) and day 28 and day 56 (B). Differentially expressed KEGG orthologs are represented by pie charts compared to non-differentially expressed KEGG orthologs in gray, where colored wedges denote phylogenetic affiliations. Colors represent phylum affiliations as follows: Actinobacteria, green; Proteobacteria, purple; Bacteroidetes, red; and Firmicutes, blue. Circle size denotes average normalized KEGG ortholog counts. Axes represent the log2-fold change (Log2FC) versus the log2 transcript counts per million (Log2CPM).
FIG 4
FIG 4
Bacterial motility and chemotaxis differentially expressed during probiotic consumption. (A) Bar charts represent log2-fold change (Log2FC) for flagellar assembly (KEGG map02040) and bacterial chemotaxis (KEGG map02030) KEGG orthologs for comparisons between transcriptome group 1 individuals at baseline and day 28 and on day 28 and day 56. Differentially expressed KEGG orthologs are denoted by black bars. Schematics of the two KEGG pathways are also shown, with differentially expressed KEGG orthologs highlighted in yellow. (B) Distribution of the normalized relative transcript abundance for the 11 KEGG orthologs differentially expressed on day 28 across the four individuals affiliated with transcriptome group 1.
FIG 5
FIG 5
In vivo expression profile for the probiotic Lactobacillus rhamnosus GG (LGG). Circular genome plots represent metagenomic (outer three tracks) and transcriptomic (inner 12 tracks) coverage at baseline (A), on day 28 during probiotic consumption (B), and on day 56, 1 month after stopping LGG consumption (C). Outer metagenomic tracks from the outermost ring are as follows: subjects 428, 419, and 408. Inner transcriptomic tracks from outermost ring to inner are as follows: subjects 421, 402, 401, 428, 419, 420, 412, 408, 409, 415, 407, and 406. Compliance for subject 406 was questionable, as reflected in the lack of recruited LGG transcripts.

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