How Bacteria Team Up to Unlock Nature's Medicine
In the intricate world of human nutrition, some of the most valuable compounds don't come ready-made from our food, but are instead unlocked by the microscopic inhabitants of our gut.
The transformation of dietary lignans into bioactive enterolignans follows a precise five-step biochemical pathway that requires coordinated effort from multiple bacterial species 3 . This process begins with plant lignans such as pinoresinol (found in olive oil and sesame seeds) and concludes with the production of enterolactone and enterodiol—the "mammalian lignans" associated with numerous health benefits 1 7 .
Bacterial Species
Eggerthella lenta
Key Enzyme/Gene
Benzyl ether reductase (BER)
Initiates the process
Bacterial Species
Blautia producta
Key Enzyme/Gene
Guaiacol lignan methyltransferase (GLM)
Removes methyl groups
Bacterial Species
Gordonibacter pamelaeae
Key Enzyme/Gene
Catechol lignan dehydroxylase (CLDH)
Executes dehydroxylation
Bacterial Species
Lactonifactor longoviformis
Key Enzyme/Gene
Not yet identified
Completes transformation
Prior to this research, scientists knew which bacteria were involved in lignan transformation but didn't understand the genetic machinery responsible. The research team, led by Elizabeth Bess, employed a multi-faceted approach to identify the genes 3 6 . They began by testing 25 different bacterial strains from the Coriobacteriia class to determine which could metabolize pinoresinol, the starting lignan 3 .
Through comparative genomics, the researchers identified a single genetic locus present in all metabolizing strains but absent in non-metabolizers 3 . This locus contained two genes: ber (benzyl ether reductase), which encodes the enzyme that performs the chemical reactions, and berR, which regulates ber's expression 3 .
To confirm ber's function, the team expressed it in E. coli—bacteria that normally cannot process lignans. The remarkable result: engineered E. coli converted 97.2% of pinoresinol to secoisolariciresinol 3 . When they mutated specific amino acids in ber's active site, this conversion dramatically decreased, providing definitive evidence that ber alone was sufficient for the first two steps of lignan metabolism 3 .
Conversion rate of pinoresinol to secoisolariciresinol by engineered E. coli expressing ber 3
| Experimental Approach | Key Finding | Significance |
|---|---|---|
| Comparative genomics | Single locus (ber/berR) conserved only in metabolizing strains | Identified candidate genes |
| Heterologous expression in E. coli | 97.2% conversion of pinoresinol to secoisolariciresinol | Confirmed ber sufficiency for first two steps |
| Active site mutation | Dramatically reduced conversion | Established essential catalytic residues |
| Gene expression analysis | ber upregulated 2670-fold with pinoresinol | Demonstrated substrate-specific regulation |
With the first two steps solved, the team turned to the remaining reactions. Since they lacked extensive strain collections for the other bacteria, they employed RNA sequencing to identify genes upregulated when each bacterium encountered its specific lignan substrate 3 .
When exposed to secoisolariciresinol, only six genes were significantly upregulated, with one—a methyltransferase they named glm—showing the strongest response 3 .
Showed massive upregulation (3893-fold) of a molybdopterin oxidoreductase gene, which they named cldh, when exposed to its substrate 3 .
A crucial question remained: were these newly identified genes actually relevant in human guts? The team analyzed human gut microbiomes from residents of Northern California and found that despite the low abundance of these specific bacteria, the genes themselves were detectable in most individuals 3 . This suggests that the lignan-metabolizing capability is widely distributed, even if the specific bacterial hosts vary between people.
The newly identified genes were detectable in most human gut microbiomes analyzed 3 .
Despite low abundance of specific bacteria, the metabolic capability persists 3 .
Lignan-metabolizing capability is widely distributed across different individuals 3 .
The genetic discoveries have direct implications for human health and nutrition.
| Research Tool | Function in Study | Experimental Role |
|---|---|---|
| Bacterial strain collections | 25 Coriobacteriia strains, including multiple E. lenta isolates | Enabled comparative genomics to identify conserved genes in metabolizers vs. non-metabolizers |
| Gnotobiotic mice | Mice with defined, simplified microbiomes | Provided controlled system to test gene importance in living hosts |
| Heterologous expression systems | Engineered E. coli producing Ber protein | Allowed functional testing of individual genes outside native hosts |
| RNA sequencing | Transcriptional profiling of bacteria exposed to lignans | Identified genes specifically upregulated during lignan metabolism |
| HPLC (High Performance Liquid Chromatography) | Separation and quantification of lignans and metabolites | Enabled precise measurement of conversion rates in experiments |
The identification of the genetic basis for lignan metabolism represents a paradigm shift in how we understand plant-microbe-human interactions. Rather than viewing bacteria as individual actors, this research highlights the importance of microbial consortia working together to unlock nutrients 6 .
This has profound implications for personalized nutrition, as individuals vary in their gut microbiome composition and thus in their ability to benefit from dietary lignans 5 .
These genetic discoveries also open new avenues for developing precision interventions targeting the gut microbiome to enhance health outcomes. Understanding exactly which genes and enzymes are involved creates opportunities to develop probiotics, prebiotics, or other therapies that optimize this valuable metabolic pathway 3 6 .
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