Large-scale genome-wide analysis links lactic acid bacteria from food with the gut microbiome

Abstract

Lactic acid bacteria (LAB) are fundamental in the production of fermented foods and several strains are regarded as probiotics. Large quantities of live LAB are consumed within fermented foods, but it is not yet known to what extent the LAB we ingest become members of the gut microbiome. By analysis of 9445 metagenomes from human samples, we demonstrate that the prevalence and abundance of LAB species in stool samples is generally low and linked to age, lifestyle, and geography, with Streptococcus thermophilus and Lactococcus lactis being most prevalent. Moreover, we identify genome-based differences between food and gut microbes by considering 666 metagenome-assembled genomes (MAGs) newly reconstructed from fermented food microbiomes along with 154,723 human MAGs and 193,078 reference genomes. Our large-scale genome-wide analysis demonstrates that closely related LAB strains occur in both food and gut environments and provides unprecedented evidence that fermented foods can be indeed regarded as a possible source of LAB for the gut microbiome.

Fig. 1. Average prevalence of LAB species from human and food microbiomes.

We report the 30 LAB species having a prevalence >0.1% in the human gut. Values are obtained from 9445 publicly available human metagenomes and stratified by multiple host conditions (i.e., body site, age category, westernized lifestyle, and continent). Age category, westernized lifestyle, and continent statistics refer to stool samples only. Food results are obtained from 303 food metagenomes. Numbers and p-values (Fisher’s test, false discovery rate correction) in Supplementary Figs. 1–4 and Supplementary Data 4. Relative abundances in Supplementary Data 2 and 3.

Fig. 2. Microbial genomes reconstructed from food metagenomes.

a Most prevalent species-level genome bins (SGBs) in 666 MAGs reconstructed from 303 food metagenomes and overlapping with human MAGs (i.e., found in at least one of the 154,723 human MAGs). Numbers in parenthesis represent the SGB IDs. b Most prevalent food SGBs not overlapping with human MAGs. kSGBs denote SGBs with at least one reference microbial genome, whereas fSGBs identify newly assembled SGBs from food metagenomes only. X-axes for a and b are in logarithmic scale. c Fraction of reference genomes per source type for the 30 selected LAB species and grouped by genera (the same plot at species-level is reported in Supplementary Fig. 6). Raw data in Supplementary Data 6 and 7.

Fig. 3. Comparative genomic analysis of the two most prevalent LAB identified in the human gut microbiome.

a S. thermophilus is a genetically diverse species both in food and human sources with MAGs reconstructed from Asian gut metagenomes enriched in Clade A (p < 1e − 10). b Lc. lactis subsp. lactis is formed by three main clusters: Cluster 1 exhibits an overall low diversity and includes mostly food genomes related to cheese and dairy fermentation; Cluster 2 is dominated by environmental and raw vegetable products and more diverse human MAGs; Cluster 3 includes only two MAGs from nunu. Phylogenetic trees were built on species-specific marker genes and report five different metadata. Multidimensional scaling (MDS) on average nucleotide identity (ANI) distance is coloured with source information.

Fig. 4. Comparative genomic analysis of relevant lactobacilli found in both food and human microbiomes.

a Lb. delbrueckii is not prevalent in the gut, and the only two subspecies found in both food and human samples are subsps. lactis and. bulgaricus. Subsps. delbrueckii, sunkii, and jakobsenii are found in food, but never reconstructed from the gut. b Lb. rhamnosus exhibits the greatest number of genomes from human isolates but is scarcely reconstructed from metagenomes. A specific cluster identifies the LGG strain. c Lb. casei/paracasei includes reference genomes identified as both Lb. casei and Lb. paracasei. We detect two main clusters both occurring in food and human samples. d Lb. helveticus exhibits three main clusters, with Cluster 1 including all the dietary supplement strains (source in green), while food genomes are predominantly spread across the other two groups. Phylogenetic trees were built on species-specific marker genes and report five different metadata. Multidimensional scaling (MDS) on average nucleotide identity (ANI) distance is coloured with source information.