Viomega: Decoding the Gut's Living Language to Revolutionize Human Health

Beyond the Microbial Census - How metatranscriptomics reveals what your microbiome is actually doing

Beyond the Microbial Census

Imagine if your gut microbiome could talk—revealing not just which microbes reside there, but what they're actively doing to influence your health. For decades, scientists studied gut bacteria through 16S rRNA sequencing, a method akin to taking a population census that records names but not occupations 1 5 . While metagenomics later revealed microbial "skill sets," it couldn't show which skills were actively used. Enter metatranscriptomics: a technology that captures the gut's real-time conversations by sequencing microbial RNA. Despite its potential, challenges like RNA degradation, cost, and computational complexity limited its use—until now. Viomega, a breakthrough automated platform, has analyzed 10,000 human stool samples, unlocking population-scale insights into diet, microbiome function, and disease 1 5 .

Did You Know?

The human gut contains about 100 trillion microorganisms - more than all the stars in the Milky Way galaxy!

Fast Fact

Viomega's platform can process RNA samples at room temperature for up to 12 days without degradation.

Why Metatranscriptomics Changes Everything

The Functional Gap in Microbiome Science

Traditional methods offer static snapshots:

  • 16S rRNA sequencing: Identifies bacterial families but misses 50% of species, ignores fungi/viruses, and reveals nothing about activity 5 .
  • Shotgun metagenomics: Catalogs all microbial genes in a sample but cannot distinguish active pathways (e.g., genes for fiber digestion may sit idle) 2 7 .

Metatranscriptomics captures messenger RNA (mRNA), the molecules microbes produce when metabolizing food, producing vitamins, or generating toxins. This reveals:

  • Real-time gene expression
  • Active metabolic pathways (e.g., inflammation triggers)
  • Responses to diet or drugs within hours 3 6 .
Comparing Microbiome Analysis Technologies
Method Target Limitations Functional Insights?
16S rRNA DNA marker Misses non-bacteria; low species resolution
Metagenomics All DNA Cannot detect active genes
Metatranscriptomics RNA transcripts Requires rapid RNA stabilization (Direct activity readout)

Source: 2 5 7

Technical Hurdles Overcome by Viomega

Early metatranscriptomics faced three bottlenecks:

  1. RNA instability: Messages degrade within seconds during sampling 4 .
  2. rRNA domination: Ribosomal RNA comprises 95% of total RNA, drowning out mRNA signals 4 6 .
  3. Computational overload: Mapping transcripts to millions of genes demands massive processing power 7 9 .

Viomega tackled these with:

Proprietary Preservatives

Stabilize RNA at room temperature for >12 days.

Subtractive Hybridization

Biotinylated DNA probes remove rRNA, boosting mRNA coverage 20-fold 1 5 .

Cloud-based Bioinformatics

Using databases of >110,000 microbial genomes and ~100 million genes 5 .

A Key Experiment: How Time-Restricted Eating Reshapes Microbial Activity

Methodology: Capturing the Gut's Diurnal Rhythm

A landmark 2025 study used metatranscriptomics to investigate time-restricted feeding (TRF)—limiting food intake to 8–10 hours daily. Researchers compared mice on high-fat diets under two regimes:

  1. All-day feeding (24-hour access)
  2. TRF (8-hour access) 3 .

Step-by-Step Workflow:

1
Sample Collection

Cecal content harvested every 4 hours over 24 hours.

2
RNA Preservation

Immediate stabilization with Viomega's preservative.

3
rRNA Depletion

Subtractive hybridization removed >90% of rRNA.

4
Library Sequencing

Illumina platforms sequenced enriched mRNA.

5
Bioinformatic Analysis
  • Reads mapped to microbial gene databases (KEGG, UniProt).
  • Differential expression analysis: Identified genes upregulated under TRF.
  • Functional validation: Engineered E. coli to express candidate genes 3 5 .

Results and Analysis: The Bile Acid Connection

Metagenomics showed no difference in microbial species between the two groups. Metatranscriptomics, however, revealed dramatic functional shifts:

  • Diurnal gene expression: 127 genes cycled rhythmically under TRF, including bsh1 (bile salt hydrolase) from Dubosiella newyorkensis.
  • Enhanced bile acid metabolism: DnBSH1 expression peaked during fasting, converting primary bile acids to secondary forms that regulate metabolism.
  • Engineered E. coli: Strains expressing DnBSH1 improved insulin sensitivity and glucose tolerance when administered to mice 3 .
Top Diurnally Expressed Genes Under TRF
Gene Function Microbe Peak Expression Health Impact
bsh1 Bile salt hydrolase Dubosiella newyorkensis Fasting phase ↑ Insulin sensitivity
abcT Amino acid transport Bacteroides thetaiotaomicron Feeding phase ↑ Nutrient absorption
fumC Short-chain fatty acid synthesis Faecalibacterium prausnitzii Feeding phase ↓ Inflammation

Source: 3

"This study proved that when we eat transforms microbiome function—independent of species composition. It also showcased how metatranscriptomics can pinpoint therapeutic targets like DnBSH1 for metabolic diseases."


Gene Expression Patterns Under Time-Restricted Feeding

Interactive chart would display here showing diurnal expression patterns

The Scientist's Toolkit: Key Reagents Driving Viomega

Essential Research Reagents in Metatranscriptomics
Reagent/Solution Function Innovation in Viomega
RNA preservative Stabilizes RNA at ambient temperature Enables mail-in stool kits; no freezing needed
Biotinylated rRNA probes Binds and removes ribosomal RNA Raises mRNA detection sensitivity 20×
Dual-barcoded adapters Labels cDNA for multiplexed sequencing Processes 94 samples/batch on liquid handlers
Cloud-based gene databases Annotates microbial genes/functions Integrates 110K genomes; 100M genes
Synthetic Positive Controls (SPCs) Quality assurance for clinical tests Amplified RNA mimics patient samples; CV <0.3%
3-Methyloxan-2-one10603-03-9C6H10O2
3-p-Tolylisoxazole13271-86-8C10H9NO
Praseodymium oxide12036-32-7O3Pr2
1-Chloroanthracene4985-70-0C14H9Cl
2-Methyl-4-octanol40575-41-5C9H20O

Source: 1 5 8

Future Frontiers: From Population Insights to Personal Health

Viomega's scale has revealed diet-microbiome-health triads:

  • High-fiber diets ↑ Roseburia expression of butyrate synthases, protecting against colitis 6 .
  • Artificial sweeteners ↑ pro-inflammatory pathways in Bacteroides within 48 hours 5 .

Next-Generation Applications:

Diagnostics

Synthetic controls (SPCs) enable clinical tests for oral cancer and IBS with 99% reproducibility 8 .

Personalized Nutrition

Predictive models of glycemic response based on microbial gene expression 6 .

Drug Discovery

Mining expressed genes for novel enzymes (e.g., lipid-modifying biocatalysts) 4 6 .

Conclusion: Listening to the Microbial Symphony

Viomega represents more than technical prowess—it's a paradigm shift. By capturing the gut microbiome's active voice, we move beyond "who's there" to "what are they doing to my health right now?" As this technology integrates with wearables and AI, it promises a future where personalized microbiome interventions—whether diets, probiotics, or RNA-based therapeutics—prevent and reverse chronic diseases. With every stool sample, we're translating microbial conversations into actionable health insights, turning the gut's whispers into a roar of possibility.

For further details on methods, see Viomega's original publication and the diurnal rhythms study.

References