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Applications | Microbiome Research

Microbiome Research and Disease Applications

Discover the secrets of the microbiome through the power of metabolomics. Unlock new insights into microbial interactions and their impact on health.

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Infectious Disease and Metabolomics

Metabolomics in Microbiome Research

Microbiome research can be challenging due to the vast diversity and complexity of microbiomes, coupled with a lack of standardized methodologies, which can contribute to variability in results. Analyzing microbiome data, often requiring specialized bioinformatics tools, presents computational challenges. Variability in microbiome composition between individuals and over time complicates establishing clear cause-and-effect relationships. Understanding the functions and interactions of microorganisms with the host is a key focus of research. Additionally, translating research findings into therapies and unraveling intricate microbiome-host interactions and environmental influences pose ongoing challenges. Nonetheless, microbiome research yields valuable insights into health, disease, and ecosystems, fostering interdisciplinary collaboration and methodological innovation.

Metabolomics contributes to microbiome research by offering valuable insights into the functional characteristics of microbiomes and their impact on host health. This field complements genomics, transcriptomics, and proteomics by focusing on the comprehensive analysis of metabolites, the small molecules within a biological system. Metabolomics identifies and quantifies metabolites produced by microorganisms in the microbiome, shedding light on their metabolic activities. It helps researchers understand the dynamic metabolic pathways, active processes, and the specific biochemicals produced, bridging the gap between genetic potential and actual contributions. Furthermore, metabolomics aids in deciphering how microbiome-produced metabolites influence the host’s physiology, providing a functional perspective on microbial-host interactions. This information is invaluable for identifying biomarkers, therapeutic targets, and understanding the impact of diet, drugs, and diseases on the microbiome and overall health.

Infectious Disease

Uncover Functional, Actionable Insights with Metabolomics

Fully understanding the myriad of ways in which the microbiome impacts human health and disease requires connecting the genomic and metabolomics dots between host and microbe. Metabolon can help researchers advance their microbiome research with global and targeted metabolomics panels designed to unravel host-microbiome associations to accelerate precision medicine.

Functional Insights
Biomarker Discovery
Therapeutic Target Identification

Functional Insights

Metabolomics provides direct insights into the metabolic activities of microorganisms within the microbiome. It reveals the specific metabolites being produced and the metabolic pathways that are active. This functional information is crucial for understanding how microorganisms interact with the host, influence health, and contribute to disease states. Metabolomics bridges the gap between genomic potential and actual metabolic processes, enhancing our understanding of microbiome functionality. A study published in Nature Genetics used whole genome sequencing combined with metabolomics to study energy balance. The randomized clinical trial results showed exactly how the diet modulated the microbiome and how the participants responded to the dietary intervention.

Corbin, K.D., Carnero, E.A., Dirks, B. et al. Host-diet-gut microbiome interactions influence human energy balance: a randomized clinical trial. Nat Commun 14, 3161 (2023). https://doi.org/10.1038/s41467-023-38778-x

Biomarker Discovery

Metabolomics facilitates the discovery of biomarkers associated with microbiome-related diseases or conditions. By identifying specific metabolites that are correlated with health or disease states, researchers can develop diagnostic tools and biomarkers for early disease detection, monitoring treatment responses, and predicting disease risk. These biomarkers have the potential to revolutionize healthcare and personalized medicine. A multiomic study of coronary artery disease found distinctly associated serum metabolome and gut microbial signatures. The researchers were about to use the data to train a metabolomics-based model to predict BMI when applied to patients. The model was able to predict diabetes mellitus and CAD severity, highlighting the utility of metabolomics for risk identification and prediction.

Talmor-Barkan, Y., Bar, N., Shaul, A.A. et al. Metabolomic and microbiome profiling reveals personalized risk factors for coronary artery disease. Nat Med 28, 295–302 (2022). https://doi.org/10.1038/s41591-022-01686-6

Therapeutic Target Identification

Metabolomics helps identify potential therapeutic targets for microbiome-related diseases. By uncovering disrupted metabolic pathways or metabolites associated with disease, researchers can develop interventions aimed at restoring a healthy balance in the microbiome. This has significant implications for the development of microbiome-based therapies, such as probiotics, prebiotics, dietary interventions, supplements, and medication to improve health outcomes and treat various conditions. A study published in Nature Medicine evaluated microbial communities in cervicovaginal lavage samples from patients with bacterial vaginosis (BV) results from an overgrowth of bacteria in the vagina. Metabolomics results lead to a treatment that combined a cystine uptake inhibitor with metronidazole to reduce the likelihood of post-treatment relapse and suggested treatments to improve women’s reproductive health.

Bloom, S.M., Mafunda, N.A., Woolston, B.M. et al. Cysteine dependence of Lactobacillus iners is a potential therapeutic target for vaginal microbiota modulation. Nat Microbiol 7, 434–450 (2022). https://doi.org/10.1038/s41564-022-01070-7

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“The gut microbiota forms complex relationships with its host organism, modulating broad aspects of host physiology including metabolism and neurobiology. Often, the connections between the gut microbiota and host physiology are easiest to decipher through presence/absence of large sectors of the microbial community, but in some cases, specific microbial features and/or taxa serve important roles in host biology.”

Lynch, J.B., Gonzalez, E.L., Choy, K. et al.
Gut microbiota Turicibacter strains differentially modify bile acids and host lipids. Nat Commun 14, 3669 (2023). https://doi.org/10.1038/s41467-023-39403-7 Available under CC BY 4.0

Elucidating a Metabolic Signature that Explains Gut-Related Changes in Human Energy Balance

Human energy balance is a crucial factor in maintaining overall health and well-being. It refers to the equilibrium between energy intake (calories consumed), energy expenditure (calories burned through metabolic processes), and energy output (energy excreted through feces and urine from undigested food). Maintaining a healthy energy balance is essential in various aspects of health, including weight management, cardiovascular health, and immune function. The gut microbiome is emerging as a key modulator of human energy balance. Despite this knowledge, studies to date lack a comprehensive quantitative evaluation of the contribution of the gut microbiome to the entire energy balance equation. Insights into modifiable factors in the microbiome might help manage conditions related to energy balance. To help fill this knowledge gap, this study used a multi-omics approach to profile fecal samples and sera from individuals in a metabolic ward. The insights from this study reveal the complex intersection of host-diet-gut microbiome factors that modulate energy balance and possibly human health.

The research group used Metabolon’s Short Chain Fatty Acids Targeted Panel to profile fecal and serum samples from individuals on a Western Diet (WD) or a microbiome-enhanced diet (MBD).1 Using Metabolon’s technology outputs, the researchers were able to establish an improved understanding of the relationship between the gut microbiome and human energy balance.

This research team conducted a controlled feeding study to detect energy balance changes in response to the diet intervention. They used an MBD, a diet designed to feed and modulate the colonic gut microbiome. They found that compared to the WD, the MBD increased daily fecal energy output consisting of undigested food. Therefore, the MBD produced a significant decrease in host metabolizable energy compared to the WD, consequently reducing the energy available to the host.

microbiology metabolomics

Figure 1. Host energy stores and energy expenditure in response to diet-gut microbiome interactions.

a–c Weight, fat mass and lean mass changes on the WD vs. MBD; n = 16 per diet. d Energy expenditure (sleep metabolic rate extrapolated to 24-h); e, f Colonic transit time and median colonic pH; n = 17 per diet for all panels. Error bars in panel c are displayed as s.e.m. P values are from linear mixed effects regression models and denote a statistically significant effect of diet on each endpoint. Source data are provided as a Source Data file.

Next, they evaluated the microbial phenotype associated with host energy balance. 16S rRNA sequencing of the participants’ gut microbiome revealed that the MDB changed the microbiome composition, increasing the abundance of SCFA-producing bacteria. They found that an increase in fecal and serum SCFA content, including acetic acid, propionic acid, and butyric acid paralleled diet-induced changes in microbial composition. Conversely, the WD starved the gut microbes because the host had digested and absorbed more metabolizable energy in the gastrointestinal tract. Changes in the microbiome due to the MBD were accompanied by a modest weight/body composition change and significant changes in the host’s enteroendocrine system.

This study integrated metabolomics and profiling of the gut microbiome to understand how the gut microbiome modulates energy balance. Metabolon helped elucidate the complex host-diet-microbiome interplay that modulates human energy balance. The research team found that the gut microbiome can serve as a target for personalized medicine. In this case, optimizing SCFA production through diet could promote a favorable energy balance and improve overall health.

Corbin, K.D., Carnero, E.A., Dirks, B. et al. Host-diet-gut microbiome interactions influence human energy balance: a randomized clinical trial. Nat Commun 14, 3161 (2023). https://doi.org/10.1038/s41467-023-38778-x

Microbiology Publications and Citations

Metabolon has contributed extensively to publications ranging from basic research to clinical trials.

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