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Figure 2: Aspects of Prevotella and Faecalibacterium at different levels of resolution highlight the complexity of diet-microbe associations, each showing ties with many dietary variables, but varying in direction and strength by country.

Analysis shows bacterial strains and geography are critical for understanding personalized nutrition

The relationship between what we eat and the trillions of bacteria living in our gut has emerged as one of the most promising frontiers in personalized medicine and nutrition. Individual gut microbiomes play a crucial role in determining how our bodies process food, stay healthy and resist disease. As unique as the gut microbiome’s composition is to a specific individual, so are the patterns that exist within one’s cultural context and eating habits, creating a challenge in discovering meaningful connections between the microbes and lifestyles of diverse populations around the world.

A UC San Diego study published in mSystems, entitled, “A three-country analysis of the gut microbiome indicates taxon associations with diet vary by taxon resolution and population,” addresses this challenge by analyzing gut microbiome data from 1,177 individuals across the United States, United Kingdom and Mexico. The research was led by the UC San Diego Center for Microbiome Innovation (CMI), Danone Research and Innovation, and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico. This international partnership enabled the researchers to examine how dietary associations with gut bacteria vary not only between different levels of bacterial classification but also across different populations with distinct dietary patterns and cultural backgrounds.

“Our motivation for this research was to capture a more global perspective on the relationship between the human gut microbiome, diet and health,” noted Lora Khatib, first author and Neuroscience Graduate Program PhD student with the Knight Lab at UC San Diego. “We aimed to better understand both universal and population-specific microbial patterns, especially how taxa may interact with culturally distinct diets and lifestyles in ways that could influence health outcomes.”

The research utilized The Microsetta Initiative platform, incorporating dietary questionnaires from participants in all three countries and advanced metagenomic sequencing techniques to analyze fecal samples. Rather than relying on traditional methods that identify bacteria only at broad genus levels, the researchers used cutting-edge computational tools to resolve bacterial communities down to individual strains. Their analysis focused on two important bacterial genera commonly associated with diet and health, Prevotella and Faecalibacterium. When the researchers examined these bacteria at the genus level, they remarkably found neither correlated strongly with dietary information, nor were they consistent across different populations. However, when they analyzed the same data at the strain level, a more complex pattern emerged.

While many of the Prevotella strains showed dietary correlations, these associations were specific to both the strain and population studied. For example, the same strain may be positively associated with vegetable intake in one population while showing an association with meat intake in another. Conversely, nearly all of the Faecalibacterium strains showed dietary correlations, many of which were consistent across different strains and positively associated with healthy dietary patterns. The study also revealed that geographic location had the strongest effect on overall microbiome composition, as their machine learning algorithms were able to predict a person’s country of origin with strong accuracy, based solely on their gut bacterial profile. 

This study underscores the importance of diverse sampling and high-resolution data in microbiome research, and represents a remarkable step toward understanding the complex relationship between individuals’ diet, geographic location and gut microbiomes. The research team plans to expand the analysis to include samples from Japan and Spain to further diversify their dataset, test patterns observed from this three-country study and deepen their understanding of how gut microbiome-diet relationships at the strain level differ across populations with distinct dietary and lifestyle patterns.

Andrew Bartko, corresponding author and executive director of CMI, emphasized, “This work highlights the need for more diverse and representative microbiome research across different populations and supports the development of personalized nutrition strategies. In the future, this kind of research could inform tailored dietary recommendations that take into account both a person’s gut microbiome and their cultural eating patterns, ultimately helping to prevent or manage chronic diseases.”

Additional co-authors include Se Jin Song, Amanda H. Dilmore, Jon G. Sanders, Caitriona Brennan, Alejandra Rios Hernandez, Tyler Myers, Renee Oles, Sawyer Farmer, Charles Cowart, Amanda Birmingham, Edgar A. Diaz, Kat Gilbert, Promi Das, Brent Nowinski, Mackenzie Bryant, Caitlin Tribelhorn, Karenina Sanders-Bodai, Antonio González, Daniel McDonald and Rob Knight of UC San Diego; Oliver Nizet of Johns Hopkins University; Nicole Litwin of Crohn’s and Colitis Foundation, New York; Soline Chaumont, Jan Knol, Guus Roeselers, Manolo Laiola, Sudarshan A. Shetty, Patrick Veiga, Julien Tap, Muriel Derrien, Hana Koutnikova, Aurélie Cotillard and Christophe Lay of Danone Global and Innovation; and Armando R. Tovar, Nimbe Torres and Liliana Arteaga of Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán.

The Center for Microbiome Innovation is proud to include Se Jin Song, Andrew Bartko and Rob Knight on its leadership team.

About the UC San Diego Center for Microbiome Innovation (CMI): CMI inspires and sustains vibrant collaborations between industry leaders and interdisciplinary teams of UC San Diego researchers to fuel discovery and innovation in the world of microbiome science. The Center encompasses a diverse range of expertise in microbiome sampling, -omics technologies and data analysis, using high-performance computing environments, statistical frameworks and AI methodologies. If you are interested in discussing potential partnership opportunities with the CMI team, contact cmiinfo@ucsd.edu for more information.

This work was funded by Danone Nutricia Research and the Center for Microbiome Innovation and supported by The Microsetta Initiative.

Figure 2: Aspects of Prevotella and Faecalibacterium at different levels of resolution highlight the complexity of diet-microbe associations, each showing ties with many dietary variables, but varying in direction and strength by country. (a) Heatmap shows t-scores and P-values for testing the correlation between the nucleotide diversity in sGBs and dietary variables, pooled per individual by bacterial genus. (b) Bar plots show the number of significant correlations between each bacterial genus and dietary variables across all participants (purple), as well as within each country: US (blue), UK (orange), and Mexico (green). (c) An association map shows the dietary variables that were significantly correlated with the log ratio of each Prevotella sGB to the sum of all Prevotella (top) and each Faecalibacterium sGB to the sum of all Faecalibacterium (bottom) in the full data set and stratified by country, after accounting for the variation explained by covariates (cohort, BMI, antibiotic history, and level of well-being). Multiple comparisons were corrected using the Benjamini-Hochberg method with a 5% False Discovery Rate (FDR).

Photograph of sampling devices used to collect surface swabs throughout the ISS. Image credit: NASA.

Environmental surveillance of the ISS microbiome can offer indirect insights into crew health by detecting human-health related microbial genomes

As space exploration and the mission to advance science drives us deeper into space, humans are venturing further from our home planet and further into foreign ecosystems. Exiting our planet, astronauts encounter alien and artificial environments that bring discoveries, challenges and implications for human culture and biology. The same human-made environments which sustain our health and stamina away from our home planet also pose significant challenges, as these artificial environments are both purposefully and potentially adversely sequestered from our natural habitat.

To investigate these artificial environments, space flight conditions and the effects on crewmembers’ health, a recent study explored the microbes and metabolites throughout the United States Orbital Segment (USOS) of the International Space Station (ISS). The study’s goal was to create the most comprehensive dataset on spatial distribution of the chemicals and microbes of the ISS. The research was led by Rodolfo Salido Benítez and Nina Zhao, with support from Center for Microbiome Innovation (CMI) and researchers at UC San Diego, California Institute of Technology and NASA. The research was published in Cell journal on February 27, 2025 in an article entitled, “The International Space Station Has a Unique and Extreme Microbial and Chemical Environment Driven by Use Patterns.” 

Environmental surface samples from the USOS were analyzed and visualized via 3D models of the ISS to survey the sources of molecules on surfaces and provide a detailed look at the interior surface conditions of the space station. The mapping unveiled how the chemistry and microbiology of a synthesized environment in space compares to our environments on Earth. “For decades, space agencies worldwide have monitored the microbiome of the ISS, but this study provides an unprecedented, high-resolution, three-dimensional map of both microbial and chemical landscapes across the station’s interior surfaces,” highlighted CMI Faculty Director Rob Knight, one of the paper’s corresponding authors. “By covering nearly 100 times more sampled surfaces at a single time point than previous studies, this dataset offers an invaluable resource for understanding how space habitats shape microbial communities, and how these changes may impact both microbial life and astronaut health over time.”

Figure S3. Source tracking estimates of bacterial source contributions by module. Box plots show SourceTracking2 estimates of potential microbial source contributions to the environmental microbiota in the ISS; box boundaries denote 25th and 75th percentiles whereas the whiskers extend up to 1.5 times the IQR. Panels A-K show the source contribution distributions per microbial source (specified in the Y axis in each panel), across sampled modules (in the X axis). L) 3D visualization of the distribution of urine SourceTracker2 signals on surfaces in Node 3. Circular disc targets represent sampled locations. Perceptual colorbar indicated on the bottom right corner with low intensity signals in darker colors (purple) and high intensity signals in lighter colors (yellow). Sampled surfaces with no color overlay represent samples that were removed from the microbiota and microbiome analyses due to KatharoSeq filtering. The visualization displays the Waste and Hygiene Compartment (WHC) on the left and the exercise treadmill on the right. Highest estimated contribution of urine related microbes is located directly on surfaces of the WHC. M) 3D visualization of the distribution of feces SourceTracker2 signals on surfaces in Node 3. Surprisingly, some of the strongest feces signals are around the WHC but not directly on its surfaces. Feces signals also appear close to the exercise treadmill. N) Visualization of the distribution of oral cavity SourceTracker2 signals on surfaces in Node 1. High intensity signals are observed around the dining table, on the food storage overhead, and on the racks opposite to the dining table (racks on port), where food heating and rehydration takes place O) Visualization of the distribution of food SourceTracker2 signals on surfaces in Node 1. High intensity signals are observed around the dining table and on the food storage racks overhead, which could be attributed to food particles being released while crew-members eat, given that food is stored in airtight containers. However, in contrast to the oral cavity signals, the racks opposite to the dining table (port) have limited presence of microbes related to food.

Understanding the ISS surface microbiota and metabolome required contextualizing them with other human-made, or built, environment samples. The researchers combined data from their study with samples from built environments, like rural and urban homes, offices and free-living environments across the globe collected by the Earth Microbiome Project. 

Comparing ISS bacteria, microbial composition and metabolomics data to these human-made and natural environments on Earth, like buildings and rainforests, the findings reveal a striking loss of microbial diversity and position the ISS as an extreme, human-input-dominated built environment with limited phylogenetic diversity. ISS samples were similar to those of more urbanized environments, suggesting that the ISS microbial environment is enriched with human-associated bacteria dispersed through routine indoor activity. The ISS has a much lower variety of microbes than almost any other environment, likely due to heavy cleaning and isolation—a lack of microbial diversity which could pose threats to astronauts’ immune systems. Additionally, microbial contributions from free-living terrestrial sources were minimal, suggesting astronauts lack environmental microbial exposures typical on Earth. 

The study revealed that the ISS’s different modules have distinct microbial and chemical signatures based on how they are used. Activities like eating, exercising, and personal hygiene left stronger microbial and chemical traces than tasks related to research or spacecraft maintenance. This highlights how human activities shape the environment around them—even in space. The station’s microbiota is largely dominated by human-associated microbes, particularly from the skin, while environmental microbes commonly found on Earth are almost completely absent.

While regular surveying of the ISS reveals these environments are maintained without significantly increasing health risks, potential threats to astronaut health and spacecraft integrity have been identified, including microbial species of concern and chemical contaminants exceeding terrestrial indoor levels. The paper’s authors noted these systems could benefit from intentionally fostering diverse microbial communities resembling Earth’s natural bacteria instead of relying on highly sanitized spaces. “Truly sterile environments—completely devoid of microbial life—are exceptionally rare on Earth. In space, excessive chemical decontamination may be counterproductive to maintaining a healthy ecosystem. By comparing the ISS to terrestrial habitats, our study highlights beneficial microbes that could be introduced to spacecraft as essential companions, supporting a resilient environment for long-term space habitation and exploration,” noted co-first author and Director of Laboratory Automation at Knight Lab, UC San Diego, Rodolfo Salido Benítez, PhD.

The study sheds light on the need to investigate how different environments and microbes affect our health, especially which microbes or chemicals that are important for our immune system might be missing from highly regulated spaces. These insights could inform design and maintenance tactics of future space stations with health in mind, such as zoning strategies to reduce cross-contamination between habitation and research rooms, isolating high biochemical burden areas (like those specific to exercise or hygiene) and alternative sanitation strategies to mitigate the selection of antimicrobial resistance that may result from chemical disinfection.

The authors hope their work can serve as a reference for future research on space habitation and built environments, and that scientists will come together to inform human space exploration while continuing to learn how to improve life on our home planet. Pieter Dorrestein, a CMI faculty member and co-corresponding author, offered, “We often think about chemical exposures in terms of potential hazards, but this study challenges us to consider what we’re not exposed to. As urbanization and industrialization reshape our environments, we may be losing beneficial chemical interactions that once shaped human health. Understanding these missing exposures could help us create more balanced and supportive living spaces.”

Photograph of sampling devices used to collect surface swabs throughout the ISS. Image credit: NASA.

Additional co-authors include Daniel McDonald, Helena Mannochio-Russo, Simone Zuffa, Renee E. Oles, Allegra T. Aron, Yasin El Abiead, Sawyer Farmer, Antonio González, Cameron Martino, Ipsita Mohanty, Lucas Patel, Paulo Wender Portal Gomes, Robin Schmid, Tara Schwartz, and Jennifer Zhu at UC San Diego; Ceth W. Parker and Kasthuri Venkateswaran at Jet Propulsion Laboratory, California Institute of Technology; and Michael R. Barratt, Kathleen H. Rubins, and Fathi Karouia at NASA Johnson Space Center.

CMI is proud to include Hiutung Chu and Pieter C. Dorrestein as faculty members and Rob Knight on its leadership team.

About the UC San Diego Center for Microbiome Innovation (CMI): UC San Diego is a world-leader in microbiome research, biomedical engineering, quantitative measurements and modeling, cellular and chemical imaging, drug discovery, “‘omics” sciences, and much more. CMI leverages the university’s strengths to draw interdisciplinary teams of researchers together and push the boundaries of the human understanding of microbiomes — the distinct constellations of bacteria, viruses, and other microorganisms that live within and around humans, other species, and the environment.

CMI partners with top companies in a variety of industries from around the world, creating a bridge with UC San Diego faculty, researchers, graduate students, and postdoctoral researchers to collaborate on projects that are transforming the way the microbiome is studied. Through these collaborations, we develop the talent and technology the industry needs for the future of microbiome research.

Funding: R.K. is funded in part by the NIH Pioneer Award, grant number DP1AT010885 and the Alfred P. Sloan Foundation award to develop and disseminate techniques for 3D mapping of the microbiology and metabolism of built environments (MoBeDAC), grant number G-2017-9838. L.P. is supported by the University of California San Diego Medical Scientist Training Program (NIH/NIGMS T32GM007198). Y.E. was supported by NIH 1R03OD034493-01. Research reported in this publication was supported by the Center for the Advancement of Science in Space and sponsored by the International Space Station U.S. National Laboratory under grant/agreement number UA-2019-818. This publication includes data generated at the UC San Diego IGM Genomics Center utilizing an Illumina NovaSeq 6000 that was purchased with funding from a National Institutes of Health SIG grant (#S10 OD026929).

Declaration of interests: Rob Knight is a scientific advisory board member, and consultant for BiomeSense, Inc., has equity and receives income. He is a scientific advisory board member and has equity in GenCirq. He is a consultant and scientific advisory board member for DayTwo, and receives income. He has equity in and acts as a consultant for Cybele. He is a co-founder of Biota, Inc., and has equity. He is a cofounder of Micronoma, and has equity and is a scientific advisory board member. Daniel McDonald is a consultant for, and has equity in, BiomeSense, Inc. The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. Pieter C. Dorrestein is the scientific advisor to and holds equity in Sirenas and Cybele Microbiome, and is scientific co-founder, scientific advisor, and has equity in Ometa Labs, Arome, and Enveda (with approval by UC San Diego).