The microbiome refers to an intricate community of microorganisms, from bacteria to fungi to viruses and even their genetic material, that reside within a specific environment, like the human body (watch Panome Bio’s Webinar to learn more about microbiome).
In the context of human health, this term often falls on the gut microbiome, the vast community of microbes residing within the digestive tract. This gut microbiome is more than a collection of microbes. It is a dynamic, metabolically active ecosystem that profoundly influences host physiology, from digestion and immune regulation to neural communication and nutrient metabolism. The microbiome plays a crucial role in maintaining health, but what happens when this intricate system is disrupted? Understanding the biochemical consequences of microbiome metabolomics and its disruption is key to understand health, disease, and personalized interventions.
Figure 1: Microbiome metabolomics
Understanding Key Metabolites in Microbiome Function:
- Bile Acids: These essential molecules, synthesized in the liver, support fat digestion and absorption. The gut microbiome plays a critical role in their metabolism, transforming primary bile acids from the liver into secondary bile acids, which have diverse physiological effects, including regulating gut health and inflammation.
- Short-Chain Fatty Acids (SCFAs): These are vital compounds like butyrate, propionate, and acetate, produced when gut bacteria ferment dietary fibers. SCFAs are a primary energy source for colon cells, support gut barrier integrity, and influence immune responses.
- Intermediate Compounds: These compounds include nutrient-related metabolites, vitamins or steroids, where the gut microbiome can influence mineral absorption, synthesize vitamins or produce steroids.
Advanced microbiome analysis with Next-Generation Metabolomics via liquid chromatography-mass spectrometry (LC-MS) offers a powerful lens to investigate these effects. With its untargeted metabolomics profiling capabilities, Panome Bio reveals the biochemical consequences of the gut microbiome perturbations, like antibiotic exposure, transforming complex metabolic data into important insights.
A New Era of Microbiome Metabolomics Profiling at Unmatched Depth
Figure 2: Case Study workflow and detected metabolites within samples.
To explore how antibiotics reshape the host microbiome interaction and thus the metabolic landscape, mice were treated with a broad-spectrum antibiotic cocktail, while control animals received saline. After 14 days, fecal samples were collected and analyzed using Panome Bio’s untargeted metabolomics platform. This comprehensive approach captured a wide spectrum of polar, non-polar (lipid), and intermediate metabolites, including bile acids, dietary compounds, steroids, and vitamins, offering an unparalleled view into the microbiome’s chemical footprint.
Profiling of the host fecal samples revealed 4,277 unique metabolites, delivering unmatched depth of the data for precise profiling across key metabolite classes:
- 1,755 polar compounds, including amino acids and dipeptides, reflecting protein metabolism and microbial dynamics.
- 1,100 non-polar lipids, including ceramides and glycerophosphoethanolamines, essential for cell signaling and membrane integrity.
- 1,422 intermediate compounds, such as bile acids, vitamins, and dietary molecules, offering a comprehensive view of gut–liver axis interactions.
Panome Bio’s high-resolution heatmaps and clustering analyses clearly differentiated antibiotic-treated mice from controls. These distinct patterns represent disrupted processes by microbiome loss, resulting in systemic metabolic shifts, highlighting far-reaching consequences of microbial imbalance. Quantifying chemical diversity displayed a significant reduction in lipid and bile acid diversity following antibiotic treatment. Interestingly polar metabolite diversity increased, likely due to accumulation of unmetabolized compounds, that would be broken down by a healthy microbiome. These shifts underscore how dysbiosis alters not just microbial presence, but also their biochemical contributions. Dysbiosis describes an imbalance or disruption in the microbial community within the gut. Issues with dysbiosis can include a loss of beneficial bacteria, an overgrowth of harmful microbes, or a reduction in overall microbial diversity. Such imbalances are linked to various health problems, including digestive disorders, inflammatory conditions, metabolic diseases, and compromised immune function.
A key example of this is bile acid metabolism. Antibiotic treatment disrupted the conversion process of bile acid into secondary bile acid, with increased levels of tauro-α-muricholic acid (T-α-MCA) and decreased levels of free cholic acid (CA) and α-muricholic acid (α-MCA). These changes suggest impaired microbial deconjugation and reflect a breakdown in microbiome functionality.
The disruption doesn’t stop at bile acids. Further metabolomic profiling uncovered additional consequences of microbiome depletion. There was a marked accumulation of oligosaccharides like raffinose and stachyose, highlighting the loss of microbial enzymes needed for their digestion. At the same time, altered polyphenol metabolism emerged, with enriched levels of sulfated isoflavones, normally transformed into beneficial compounds by gut microbiome. Perhaps most critical was the depletion of short-chain fatty acids (SCFAs) such as butyrate, propionate, and acetate, which are vital for energy harvest, intestinal health, and immune regulation. These findings demonstrate how microbial loss directly affects host digestion, metabolism, and inflammation control.
Antibiotic-induced microbiome loss triggered widespread changes across 39 metabolic pathways. Key lipid pathways were significantly affected. Fatty acyl carnitines and diacylglycerophosphocholines were upregulated, possibly as compensatory mechanisms in response to lost microbial SCFA production. In contrast, crucial membrane lipids like ceramides and phospholipids were depleted, which are essential for maintaining epithelial integrity and proper cell signaling, linking microbiome loss to intestinal barrier dysfunction and systemic inflammation.
Figure 3: Top 25 metabolic pathway enrichment in fecal samples from the case study
These findings tell a powerful story. Panome Bio’s Next-Generation Metabolomics platform goes beyond data collection, it offers a clear clinical and translational roadmap. The functional collapse of the microbiome leads to the loss of metabolic diversity, particularly in bile acid and lipid pathways. The host’s metabolism becomes reprogrammed, compromising energy production, nutrient absorption, and signaling pathways. Critically, emerging biomarkers like ceramide depletion offer clear indicators of dysbiosis and new targets for therapeutic intervention.
Figure 4: Systemic Impact of Microbiome Disruption.
In short, Panome Bio transforms the invisible biochemical consequences of microbiome disruption into clear, actionable insights, driving the next generation of microbiome-based research and innovation.
Read the full application reportDownload the Microbiome Symposium poster Learn more about our microbiome capabilities