An infant gut microbiome cross-feeding system reconstructed from individualized cultivations with three infant fecal inocula and supplemented with the human milk oligosaccharide 2'-fucosyllactose (2'FL). Bifidobacterium breve typically cannot metabolize 2'FL on its own, but extracellular fucosidases encoded by coexisting Ruminococcus gnavus release lactose from 2'FL and unlock extensive B. breve growth. Targeted cocultures and supplementation of R. gnavus into an infant microbiome showed that R. gnavus promotes B. breve growth through HMO breakdown, demonstrating that infant HMO utilization depends on synergistic interactions among coexisting species.
Taxonomy
| Taxon | Ontology ID | Functional Roles | Abundance |
|---|---|---|---|
| Bifidobacterium breve | NCBITaxon:1685 · TaxonMech · TraitMech |
CROSS_FEEDER
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ABUNDANT |
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| Ruminococcus gnavus — ontology label: Mediterraneibacter gnavus | NCBITaxon:33038 · TaxonMech · TraitMech |
PRIMARY_DEGRADER
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ABUNDANT |
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Ecological Interactions
The graph shows only explicitly linked interaction participants. Community members without an asserted participant link are omitted; membership alone does not imply an interaction.
B. breve 2'FL Transporter Constraint
The FT-1 B. breve isolate did not grow on 2'FL or fucose alone but grew on lactose. Genomic searches found a predicted intracellular GH95 fucosidase and no identifiable 2'FL transporter. PARTIAL - this is a candidate explanation for substrate limitation, not a transporter knockout or a cause of donor hydrolysis.
Participating Taxa: Bifidobacterium breve
Metabolites: 2'-fucosyllactose (CHEBI:147155 · MediaIngredientMech · CMMMech), lactose (CHEBI:17716 · MediaIngredientMech · CMMMech)
Biological Processes:
- carbohydrate metabolic process (GO:0005975 · PathwayMech)
Evidence
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PMID:37973815 - SUPPORT (IN_VITRO)"B. breve from FT-1 cannot metabolize 2’FL"
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PMID:37973815 - SUPPORT (COMPUTATIONAL)"B. breve encoded one fucosidase, GH95, but this gene was predicted to be intracellular"
R. gnavus Extracellular Fucosidase Capacity
COMPUTATIONAL POTENTIAL - FT-1 R. gnavus encoded six fucosidase genes, two predicted to be extracellular. This supplies a candidate molecular route for 2'FL cleavage, not directly measured extracellular activity or proof that the same donor explains every infant community.
Source Taxon: Ruminococcus gnavus
Target Taxon: Bifidobacterium breve
Metabolites: 2'-fucosyllactose (CHEBI:147155 · MediaIngredientMech · CMMMech), lactose (CHEBI:17716 · MediaIngredientMech · CMMMech)
Biological Processes:
- carbohydrate metabolic process (GO:0005975 · PathwayMech)
PARTIAL - predicted extracellular fucosidases could release lactose from 2'FL, providing the proposed route for B. breve substrate access. Localization, cleavage products and enzyme necessity were not directly resolved in the inspected main paper.
PARTIAL - FT-1 R. gnavus supplies a candidate 2'FL-cleaving capacity to PT-1. Supplementation enriches B. breve, but the specific fucosidase-dependent route is inferred rather than selectively perturbed.
Evidence
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PMID:37973815 - SUPPORT (COMPUTATIONAL)"R. gnavus was the only organism besides B. breve in FT-1 whose genome encodes fucosidases "
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PMID:37973815 - SUPPORT (COMPUTATIONAL)"it encodes six fucosidase genes (three GH29 and three GH95 genes), two of which (one GH29 and one GH95 gene) were predicted to be extracellular "
R. gnavus 2'FL Hydrolysis Feeds B. breve
CROSS_FEEDINGPARTIAL - complementary monoculture growth on 2'FL, fucose and lactose, together with increased total coculture OD600, supports the authors' lactose-release cross-feeding model. Released lactose and donor-to-recipient flux were not directly measured in the inspected main methods; higher total OD does not demonstrate benefit to both partners.
Source Taxon: Ruminococcus gnavus
Target Taxon: Bifidobacterium breve
Metabolites: 2'-fucosyllactose (CHEBI:147155 · MediaIngredientMech · CMMMech), lactose (CHEBI:17716 · MediaIngredientMech · CMMMech)
Biological Processes:
- carbohydrate metabolic process (GO:0005975 · PathwayMech)
PARTIAL - proposed lactose supply could favor B. breve, whose lactose controls show faster growth and higher final density. This explains observed coculture composition as a candidate mechanism, not measured lactose flux or proof of molecular necessity.
PARTIAL - the proposed lactose-release route could mediate B. breve enrichment after R. gnavus supplementation to PT-1. The donor intervention is measured; lactose-specific mediation of enrichment, pH and diversity remains unresolved.
Evidence
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PMID:37973815 - PARTIAL (IN_VITRO)"R. gnavus can promote extensive growth of B. breve through the release of lactose from 2'FL"
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PMID:37973815 - SUPPORT (IN_VITRO)"The R. gnavus monoculture grew on 2’FL, but not the B. breve culture"
B. breve Coculture Dominance and Lactose Growth
B. breve accounted for approximately 80% of the 2'FL coculture community. Separate lactose-only controls showed faster growth and higher final density for B. breve than R. gnavus. Relative representation and total OD600 are different endpoints; these controls support but do not directly trace the proposed lactose mechanism.
Source Taxon: Ruminococcus gnavus
Target Taxon: Bifidobacterium breve
Metabolites: lactose (CHEBI:17716 · MediaIngredientMech · CMMMech)
Biological Processes:
- carbohydrate metabolic process (GO:0005975 · PathwayMech)
Evidence
-
PMID:37973815 - SUPPORT (IN_VITRO)"B. breve dominated the co-culture community (~80% of the community)"
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PMID:37973815 - SUPPORT (IN_VITRO)"B. breve had a higher growth rate and reached a higher final cell density than R. gnavus"
Individualized HMO Utilization Capacity
Infant-derived communities responded differently to 2'FL. FT-1 and PT-1 differ in predicted donor capacity and in response to R. gnavus supplementation; FT-2 has other candidate extracellular-fucosidase producers. The listed FT-1/PT-1 partners are not a universal infant-microbiome wiring diagram.
Participating Taxa: Ruminococcus gnavus, Bifidobacterium breve
Metabolites: 2'-fucosyllactose (CHEBI:147155 · MediaIngredientMech · CMMMech), lactose (CHEBI:17716 · MediaIngredientMech · CMMMech)
Biological Processes:
- carbohydrate metabolic process (GO:0005975 · PathwayMech)
Evidence
-
PMID:37973815 - SUPPORT (IN_VITRO)"microbiome responses to 2'-fucosyllactose (2'FL), a prevalent HMO and a common infant formula additive"
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PMID:37973815 - SUPPORT (IN_VITRO)"HMO utilization can vary with an individual's microbiome"
R. gnavus PT-1 2'FL Rescue
Adding the FT-1 R. gnavus isolate to PT-1 with 0.3% 2'FL enriched B. breve, accompanied by lower pH and diversity. Predicted missing fucosidase capacity offers an explanation, not proof that lactose transfer or acidification is the necessary mediator.
Source Taxon: Ruminococcus gnavus
Target Taxon: Bifidobacterium breve
Metabolites: 2'-fucosyllactose (CHEBI:147155 · MediaIngredientMech · CMMMech), lactose (CHEBI:17716 · MediaIngredientMech · CMMMech)
Biological Processes:
- carbohydrate metabolic process (GO:0005975 · PathwayMech)
Evidence
-
PMID:37973815 - SUPPORT (COMPUTATIONAL)"In PT-1, no other organisms besides B. breve encode a fucosidase"
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PMID:37973815 - SUPPORT (IN_VITRO)"B. breve was significantly enriched in the R. gnavus-positive PT-1 microbiome grown in media with 0.3% 2’FL "
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PMID:37973815 - SUPPORT (IN_VITRO)"the increase in B. breve abundance in the R. gnavus-supplemented PT-1 microbiome was correlated with a decrease in community species diversity and pH "
Knowledge gaps & discussions (1)
KNOWLEDGE_GAP OPEN Do direct lactose measurements and enzyme perturbations resolve the proposed HMO cross-feeding routes?
Main-paper growth controls, genomics and donor supplementation support the model. Extracellular localization/activity, transporter sufficiency, donor-resolved lactose flux and mediation of pH/diversity remain unresolved at this review scope. Figures, supplements, source data and genomes were not inspected. Generic lactose is grounded without selecting an anomer; assay timing discrepancies remain a separate non-graph follow-up.
Attaches to: ecological_interactions#B. breve 2'FL Transporter Constraint, ecological_interactions#R. gnavus Extracellular Fucosidase Capacity, ecological_interactions#R. gnavus 2'FL Hydrolysis Feeds B. breve, ecological_interactions#B. breve Coculture Dominance and Lactose Growth, ecological_interactions#Individualized HMO Utilization Capacity, ecological_interactions#R. gnavus PT-1 2'FL Rescue
External Resources
| Name | Repository | Resource ID |
|---|---|---|
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Primary publication for the infant HMO cross-feeding coculture
PubMed record for the Lou et al. 2023 Nature Communications paper on Bifidobacterium breve - Ruminococcus gnavus 2'FL cross-feeding. |
OTHER | PMID:37973815 |
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DOI landing page
DOI link to the Nature Communications paper. |
OTHER | doi:10.1038/s41467-023-43279-y |
Environmental Factors
| Factor | Value | Unit |
|---|---|---|
| 2'-fucosyllactose supplementation | 2'FL HMO substrate | N/A |
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