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Variations in the Post-weaning Human Gut Metagenome Profile As Result of Bifidobacterium Acquisition in the Western Microbiome.

Soverini M, Rampelli S, Turroni S, Schnorr SL, Quercia S, Castagnetti A, Biagi E, Brigidi P, Candela M - Front Microbiol (2016)

Bottom Line: According to our findings, Bifidobacterium provides the enteric ecosystem with a diverse panel of saccharolytic functions, well suited to the array of gluco- and galacto-based saccharides that abound in the Western diet.On the other hand, the metagenomic functions assigned to Treponema are more predictive of a capacity to incorporate complex polysaccharides, such as those found in unrefined plant foods, which are consistently incorporated in the Hadza diet.Finally, unlike Treponema, the Bifidobacterium metagenome functions include genes that permit the establishment of microbe-host immunological cross-talk, suggesting recent co-evolutionary events between the human immune system and Bifidobacterium that are adaptive in the context of agricultural subsistence and sedentary societies.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy and Biotechnology, University of Bologna Bologna, Italy.

ABSTRACT
Studies of the gut microbiome variation among human populations revealed the existence of robust compositional and functional layouts matching the three subsistence strategies that describe a trajectory of changes across our recent evolutionary history: hunting and gathering, rural agriculture, and urban post-industrialized agriculture. In particular, beside the overall reduction of ecosystem diversity, the gut microbiome of Western industrial populations is typically characterized by the loss of Treponema and the acquisition of Bifidobacterium as an abundant inhabitant of the post-weaning gut microbial ecosystem. In order to advance the hypothesis about the possible adaptive nature of this exchange, here we explore specific functional attributes that correspond to the mutually exclusive presence of Treponema and Bifidobacterium using publically available gut metagenomic data from Hadza hunter-gatherers and urban industrial Italians. According to our findings, Bifidobacterium provides the enteric ecosystem with a diverse panel of saccharolytic functions, well suited to the array of gluco- and galacto-based saccharides that abound in the Western diet. On the other hand, the metagenomic functions assigned to Treponema are more predictive of a capacity to incorporate complex polysaccharides, such as those found in unrefined plant foods, which are consistently incorporated in the Hadza diet. Finally, unlike Treponema, the Bifidobacterium metagenome functions include genes that permit the establishment of microbe-host immunological cross-talk, suggesting recent co-evolutionary events between the human immune system and Bifidobacterium that are adaptive in the context of agricultural subsistence and sedentary societies.

No MeSH data available.


Related in: MedlinePlus

Profile of Bifidobacterium and Treponema functions involved in the adaptation to the host environment. Polysaccharide metabolism (A); interaction with the host and immune modulation (B); adaptation to the human gastrointestinal environment (C). Color key represents reads mapped per giga-bases of the sample of origin. See Supplementary Table S1 for the list of reference genes used.
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Figure 3: Profile of Bifidobacterium and Treponema functions involved in the adaptation to the host environment. Polysaccharide metabolism (A); interaction with the host and immune modulation (B); adaptation to the human gastrointestinal environment (C). Color key represents reads mapped per giga-bases of the sample of origin. See Supplementary Table S1 for the list of reference genes used.

Mentions: We first identified the diversity of the Bifidobacterium and Treponema species in urban Italian and Hadza GM by reconstructing the full 16S rDNA gene from assembled metagenomes. Italian samples contain sequences belonging to Bifidobacterium faecale, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium coryneforme, Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium angulatum, and Bifidobacterium dentium. On the other hand, we detect the 16S rDNA sequences assigned to Treponema porcinum, Treponema bryantii, Treponema succinifaciens, Treponema parvum, and Treponema berlinense in the GM of the Hadza hunter-gatherers. However, we must acknowledge that these taxonomic assignments are limited by present whole genome for Treponema species, most of which have been characterized by work on human pathogens, rather than commensal members of the GM. Ongoing work with species-level variation should be crucial to resolving the disparities in our classification and resolution of these species and their functions in the future (Obregon-Tito et al., 2015). In order to compare the specific saccharolytic functions conferred by Bifidobacterium and Treponema in the Italian and Hadza microbiomes, we identified a total of 5.4 million of ORFs, of which 14,512 mapped to CAZymes for the Italian samples and 74,651 for the Hadza samples (Figure 1A). Notably, the Hadza metagenomes contain significantly more CAZymes per subject, in terms of ORFs assigned to CAZymes per million of reads, respect to the Italian metagenomes (mean ± SD, Hadza: 233 ± 86, Italians: 137 ± 78), as reported by Rampelli et al. (2015). We then profiled the saccharolytic repertoire of Bifidobacterium and Treponema in the Italian and Hadza GM as relative abundance at the CAZyme category level based on the coverage of taxonomically assigned contigs (Figure 2A). Bifidobacterium showed a higher presence of glycosyl transferase (GT) and carbohydrate esterase (CE), with respect to Treponema (GT relative abundance, rel. ab.: 54% for Bifidobacterium and 43% for Treponema; CE rel. ab.: 6% for Bifidobacterium and 5% for Treponema). On the other hand, Treponema were more enriched in glycoside hydrolase (GH) and carbohydrate binding module (CBM) (GH rel. ab.: 33% for Treponema and 31% for Bifidobacterium; CBM rel. ab.: 15% for Treponema and 8% for Bifidobacterium). At the CAZyme family level, we revealed the four families that constitute the core Bifidobacterium CAZyme repertoire: GH13 (GH family acting on substrates containing α-glycosidic linkages), GH3 (GH family that groups together exo-acting β-D-glucosidases, α-L-arabinofuranosidase, β-D-xylopyranosidase and N-acetyl-β-D-glucosaminidase), GT2 (GT family containing cellulose synthase, mannan synthase, and several monosaccharide-/oligosaccharide-transferases), and GT4 (GT family containing sucrose synthase, glucosyl transferase, and several phosphorylases). The sum of ORFs assigned to these four major families comprises 77% of the total detected CAZyme cohort. The relative abundance of the Bifidobacterium and Treponema CAZyme families detected in the Italian and Hadza samples reveals several differences in the potential saccharolytic functional contributions of these two microorganisms (Figure 2B). In particular, Bifidobacterium have a greater abundance of genes involved in the degradation of lactate, which is produced from pyruvate in the fermentation of simple sugar and commonly found in sour milk as well as in other lacto-fermented foods (family GH2). This finding also corresponds to the exclusive contribution of dairy carbohydrates (∼5% of total carbohydrates), in the Italian cohort diet (Supplementary Table S2). Emphasis on monosaccharide catabolism is evidenced by enrichment in gene families containing enzymes that metabolize mannose, xylose and arabinose (GH2, GH31, and GH43), which are highly represented in plant and fruit glycans. As a variety of genes were also found that are involved in the degradation of α- and β-glucans (GH3 and GH31), this illustrates an ability of Bifidobacterium to retrieve energy also from more complex carbohydrates that are commonly present in the cellulosic biomass of plant foods in the Italian diet: salads, fruits, nuts, cereals and their product derivatives. In addition, Bifidobacterium are also enriched in genes involved in the catabolism of sucrose (GH31), which is widely distributed in nature, but robustly manifest in the industrial food products that are consumed daily by most urban populations. Further evidence of these functions comes from detection of a higher abundance of CBM families for lactose, galactose and β-glucans (CBM4, CBM13, and CBM32) in Bifidobacterium, with respect to Treponema. In contrast, the CAZyme profile of Treponema within the Hadza metagenome is mainly devoted to degradation of glucans, galactans, and fructans (GH16, GH32, and GH53), which are sugar polymers that comprise hemicellulose (galactans) and inulin (fructans). The monosaccharide of galactans, galactose, is also expressed in mucilages and glycoproteins that derive from the human host, as well as a number of vegetable-derived carbohydrates. Both sugar polymers are largely implicit in difficult-to-digest plant polysaccharides that escape small intestine absorption and are instead fermented by the colonic microbiota. The Hadza diet is replete with such unrefined plant foods that contain indigestible polysaccharides such as berries, baobab fruit, and particularly tubers (Schnorr et al., 2015). Treponema are also enriched in two CAZyme α-amylase families (GH57 and GH77), which are unlike the typical α-amylase GH13 family because they have a conserved trans-glycosylating region (MacGregor et al., 2001). Finally, Treponema are better equipped to metabolize peptidoglycans due to a wide range of acetylglucosaminases and peptidoglycan lyases (GH23, GH73, and GH109). These activities were confirmed by the detection of high levels of CBM families for peptidoglycans and α-glucans (CBM50 and CBM48). To specifically investigate the effective differences in polysaccharide-degrading repertoires between Bifidobacterium and Treponema metagenome functions, we aligned the reads of Italian and Hadza samples to a custom database containing the sequences for alpha-amylase, beta-galactosidase, mannanase, cellulase, pectinase, and xylanase. The taxonomic specificity of the aligned reads was verified by blasting the sequences to the nucleotide database of NCBI (Figure 1B). Unlike Treponema, which appears to be functionally equipped to derive energy from a broad spectrum of polysaccharides through increased relative representation of pectinase, xylanase, and cellulase, the polysaccharide-degrading functions assigned to Bifidobacterium are enriched in genes coding for β-galactosidase and mannanase (Figure 3). Interestingly, both genera are configured to hydrolyze 1–4 α-glycosidic bonds (via α-amylase) to a similar degree. The catabolic configurations of Bifidobacterium and Treponema for polysaccharides are reflective of differences in dietary carbohydrates of Italians and Hadza: pasta, legumes, milk, and dairy products, versus berries, tubers, baobab, and honey, respectively, (Supplementary Table S3).


Variations in the Post-weaning Human Gut Metagenome Profile As Result of Bifidobacterium Acquisition in the Western Microbiome.

Soverini M, Rampelli S, Turroni S, Schnorr SL, Quercia S, Castagnetti A, Biagi E, Brigidi P, Candela M - Front Microbiol (2016)

Profile of Bifidobacterium and Treponema functions involved in the adaptation to the host environment. Polysaccharide metabolism (A); interaction with the host and immune modulation (B); adaptation to the human gastrointestinal environment (C). Color key represents reads mapped per giga-bases of the sample of origin. See Supplementary Table S1 for the list of reference genes used.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940381&req=5

Figure 3: Profile of Bifidobacterium and Treponema functions involved in the adaptation to the host environment. Polysaccharide metabolism (A); interaction with the host and immune modulation (B); adaptation to the human gastrointestinal environment (C). Color key represents reads mapped per giga-bases of the sample of origin. See Supplementary Table S1 for the list of reference genes used.
Mentions: We first identified the diversity of the Bifidobacterium and Treponema species in urban Italian and Hadza GM by reconstructing the full 16S rDNA gene from assembled metagenomes. Italian samples contain sequences belonging to Bifidobacterium faecale, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium coryneforme, Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium angulatum, and Bifidobacterium dentium. On the other hand, we detect the 16S rDNA sequences assigned to Treponema porcinum, Treponema bryantii, Treponema succinifaciens, Treponema parvum, and Treponema berlinense in the GM of the Hadza hunter-gatherers. However, we must acknowledge that these taxonomic assignments are limited by present whole genome for Treponema species, most of which have been characterized by work on human pathogens, rather than commensal members of the GM. Ongoing work with species-level variation should be crucial to resolving the disparities in our classification and resolution of these species and their functions in the future (Obregon-Tito et al., 2015). In order to compare the specific saccharolytic functions conferred by Bifidobacterium and Treponema in the Italian and Hadza microbiomes, we identified a total of 5.4 million of ORFs, of which 14,512 mapped to CAZymes for the Italian samples and 74,651 for the Hadza samples (Figure 1A). Notably, the Hadza metagenomes contain significantly more CAZymes per subject, in terms of ORFs assigned to CAZymes per million of reads, respect to the Italian metagenomes (mean ± SD, Hadza: 233 ± 86, Italians: 137 ± 78), as reported by Rampelli et al. (2015). We then profiled the saccharolytic repertoire of Bifidobacterium and Treponema in the Italian and Hadza GM as relative abundance at the CAZyme category level based on the coverage of taxonomically assigned contigs (Figure 2A). Bifidobacterium showed a higher presence of glycosyl transferase (GT) and carbohydrate esterase (CE), with respect to Treponema (GT relative abundance, rel. ab.: 54% for Bifidobacterium and 43% for Treponema; CE rel. ab.: 6% for Bifidobacterium and 5% for Treponema). On the other hand, Treponema were more enriched in glycoside hydrolase (GH) and carbohydrate binding module (CBM) (GH rel. ab.: 33% for Treponema and 31% for Bifidobacterium; CBM rel. ab.: 15% for Treponema and 8% for Bifidobacterium). At the CAZyme family level, we revealed the four families that constitute the core Bifidobacterium CAZyme repertoire: GH13 (GH family acting on substrates containing α-glycosidic linkages), GH3 (GH family that groups together exo-acting β-D-glucosidases, α-L-arabinofuranosidase, β-D-xylopyranosidase and N-acetyl-β-D-glucosaminidase), GT2 (GT family containing cellulose synthase, mannan synthase, and several monosaccharide-/oligosaccharide-transferases), and GT4 (GT family containing sucrose synthase, glucosyl transferase, and several phosphorylases). The sum of ORFs assigned to these four major families comprises 77% of the total detected CAZyme cohort. The relative abundance of the Bifidobacterium and Treponema CAZyme families detected in the Italian and Hadza samples reveals several differences in the potential saccharolytic functional contributions of these two microorganisms (Figure 2B). In particular, Bifidobacterium have a greater abundance of genes involved in the degradation of lactate, which is produced from pyruvate in the fermentation of simple sugar and commonly found in sour milk as well as in other lacto-fermented foods (family GH2). This finding also corresponds to the exclusive contribution of dairy carbohydrates (∼5% of total carbohydrates), in the Italian cohort diet (Supplementary Table S2). Emphasis on monosaccharide catabolism is evidenced by enrichment in gene families containing enzymes that metabolize mannose, xylose and arabinose (GH2, GH31, and GH43), which are highly represented in plant and fruit glycans. As a variety of genes were also found that are involved in the degradation of α- and β-glucans (GH3 and GH31), this illustrates an ability of Bifidobacterium to retrieve energy also from more complex carbohydrates that are commonly present in the cellulosic biomass of plant foods in the Italian diet: salads, fruits, nuts, cereals and their product derivatives. In addition, Bifidobacterium are also enriched in genes involved in the catabolism of sucrose (GH31), which is widely distributed in nature, but robustly manifest in the industrial food products that are consumed daily by most urban populations. Further evidence of these functions comes from detection of a higher abundance of CBM families for lactose, galactose and β-glucans (CBM4, CBM13, and CBM32) in Bifidobacterium, with respect to Treponema. In contrast, the CAZyme profile of Treponema within the Hadza metagenome is mainly devoted to degradation of glucans, galactans, and fructans (GH16, GH32, and GH53), which are sugar polymers that comprise hemicellulose (galactans) and inulin (fructans). The monosaccharide of galactans, galactose, is also expressed in mucilages and glycoproteins that derive from the human host, as well as a number of vegetable-derived carbohydrates. Both sugar polymers are largely implicit in difficult-to-digest plant polysaccharides that escape small intestine absorption and are instead fermented by the colonic microbiota. The Hadza diet is replete with such unrefined plant foods that contain indigestible polysaccharides such as berries, baobab fruit, and particularly tubers (Schnorr et al., 2015). Treponema are also enriched in two CAZyme α-amylase families (GH57 and GH77), which are unlike the typical α-amylase GH13 family because they have a conserved trans-glycosylating region (MacGregor et al., 2001). Finally, Treponema are better equipped to metabolize peptidoglycans due to a wide range of acetylglucosaminases and peptidoglycan lyases (GH23, GH73, and GH109). These activities were confirmed by the detection of high levels of CBM families for peptidoglycans and α-glucans (CBM50 and CBM48). To specifically investigate the effective differences in polysaccharide-degrading repertoires between Bifidobacterium and Treponema metagenome functions, we aligned the reads of Italian and Hadza samples to a custom database containing the sequences for alpha-amylase, beta-galactosidase, mannanase, cellulase, pectinase, and xylanase. The taxonomic specificity of the aligned reads was verified by blasting the sequences to the nucleotide database of NCBI (Figure 1B). Unlike Treponema, which appears to be functionally equipped to derive energy from a broad spectrum of polysaccharides through increased relative representation of pectinase, xylanase, and cellulase, the polysaccharide-degrading functions assigned to Bifidobacterium are enriched in genes coding for β-galactosidase and mannanase (Figure 3). Interestingly, both genera are configured to hydrolyze 1–4 α-glycosidic bonds (via α-amylase) to a similar degree. The catabolic configurations of Bifidobacterium and Treponema for polysaccharides are reflective of differences in dietary carbohydrates of Italians and Hadza: pasta, legumes, milk, and dairy products, versus berries, tubers, baobab, and honey, respectively, (Supplementary Table S3).

Bottom Line: According to our findings, Bifidobacterium provides the enteric ecosystem with a diverse panel of saccharolytic functions, well suited to the array of gluco- and galacto-based saccharides that abound in the Western diet.On the other hand, the metagenomic functions assigned to Treponema are more predictive of a capacity to incorporate complex polysaccharides, such as those found in unrefined plant foods, which are consistently incorporated in the Hadza diet.Finally, unlike Treponema, the Bifidobacterium metagenome functions include genes that permit the establishment of microbe-host immunological cross-talk, suggesting recent co-evolutionary events between the human immune system and Bifidobacterium that are adaptive in the context of agricultural subsistence and sedentary societies.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy and Biotechnology, University of Bologna Bologna, Italy.

ABSTRACT
Studies of the gut microbiome variation among human populations revealed the existence of robust compositional and functional layouts matching the three subsistence strategies that describe a trajectory of changes across our recent evolutionary history: hunting and gathering, rural agriculture, and urban post-industrialized agriculture. In particular, beside the overall reduction of ecosystem diversity, the gut microbiome of Western industrial populations is typically characterized by the loss of Treponema and the acquisition of Bifidobacterium as an abundant inhabitant of the post-weaning gut microbial ecosystem. In order to advance the hypothesis about the possible adaptive nature of this exchange, here we explore specific functional attributes that correspond to the mutually exclusive presence of Treponema and Bifidobacterium using publically available gut metagenomic data from Hadza hunter-gatherers and urban industrial Italians. According to our findings, Bifidobacterium provides the enteric ecosystem with a diverse panel of saccharolytic functions, well suited to the array of gluco- and galacto-based saccharides that abound in the Western diet. On the other hand, the metagenomic functions assigned to Treponema are more predictive of a capacity to incorporate complex polysaccharides, such as those found in unrefined plant foods, which are consistently incorporated in the Hadza diet. Finally, unlike Treponema, the Bifidobacterium metagenome functions include genes that permit the establishment of microbe-host immunological cross-talk, suggesting recent co-evolutionary events between the human immune system and Bifidobacterium that are adaptive in the context of agricultural subsistence and sedentary societies.

No MeSH data available.


Related in: MedlinePlus