What Is: The Human Microbiome

The Human Microbiome
Image Credit: Scientific Frontline stock image

The Invisible Organ

The human body is not a sterile, solitary entity. It is a dense, complex, and dynamic ecosystem. Each individual serves as a host to a vast community of microorganisms, collectively known as the human microbiota. This community, which resides in and on the body, is estimated to comprise between 10 trillion and 100 trillion symbiotic microbial cells. Early estimates, which have become a cornerstone of the field, suggested these microbial cells outnumber human cells by a ratio of ten to one. While more recent analyses propose a ratio closer to 1:1, the sheer scale of this microbial colonization remains staggering. These microbial cells, though only one-tenth to one-hundredth the size of a human cell, may account for up to five pounds of an adult's body weight.

This vast microbial community is not a passive passenger. It functions as a "virtual organ" of the body, or more precisely, a "metabolic organ". It is so deeply integrated into our physiology that we are dependent on it for essential life functions, including digestion, immune system development, and the production of critical nutrients.

Rebalancing the Gut: How AI Solved a 25-Year Crohn’s Disease Mystery

Electron micrographs show how macrophages expressing girdin neutralize pathogens by fusing phagosomes (P) with the cell’s lysosomes (L) to form phagolysosomes (PL), compartments where pathogens and cellular debris are broken down (left). This process is crucial for maintaining cellular homeostasis. In the absence of girdin, this fusion fails, allowing pathogens to evade degradation and escape neutralization (right).
Image Credit: UC San Diego Health Sciences

The human gut contains two types of macrophages, or specialized white blood cells, that have very different but equally important roles in maintaining balance in the digestive system. Inflammatory macrophages fight microbial infections, while non-inflammatory macrophages repair damaged tissue. In Crohn’s disease — a form of inflammatory bowel disease (IBD) — an imbalance between these two types of macrophages can result in chronic gut inflammation, damaging the intestinal wall and causing pain and other symptoms. 

Researchers at University of California San Diego School of Medicine have developed a new approach that integrates artificial intelligence (AI) with advanced molecular biology techniques to decode what determines whether a macrophage will become inflammatory or non-inflammatory. 

The study also resolves a longstanding mystery surrounding the role of a gene called NOD2 in this decision-making process. NOD2 was discovered in 2001 and is the first gene linked to a heightened risk for Crohn’s disease.

Dusty air is rewriting your lung microbiome

UCR researcher collecting dust from the Salton Sea.
Photo Credit: Linton Freund/UCR

Dust from California’s drying Salton Sea doesn’t just smell bad. Scientists from UC Riverside found that breathing the dust can quickly re-shape the microscopic world inside the lungs. 

Genetic or bacterial diseases have previously been shown to have an effect on lung microbes. However, this discovery marks the first time scientists have observed such changes from environmental exposure rather than a disease. 

Published in the journal mSphere, the study shows that inhalation of airborne dust collected close to the shallow, landlocked lake alters both the microbial landscape and immune responses in mice that were otherwise healthy.

“Even Salton Sea dust filtered to remove live bacteria or fungi is altering what microbes survive in the lungs,” said Mia Maltz, UCR mycologist and lead study author. “It is causing deep changes to our internal environment.”

Microbes at Red Sea vents show how life and geology shape each other

Microscopic images of the studied microbes.
Image Credit: Courtesy of King Abdullah University of Science and Technology

A new study led by King Abdullah University of Science and Technology (KAUST) Professor Alexandre Rosado has revealed an unusual microbial world in the Hatiba Mons hydrothermal vent fields of the central Red Sea, a site first discovered by one of his co-authors and colleagues, Assistant Professor Froukje M. van der Zwan. 

Published in Environmental Microbiome, the study delivers the first "genome-resolved" analysis of these hydrothermal systems, providing an unprecedented view into both the types of microbes present and the metabolic functions that sustain them. 

“Microbes from the Hatiba Mons fields show remarkable metabolic versatility,” said KAUST Ph.D. student and lead author of the study, Sharifah Altalhi. “By understanding their functions, we can see how life shapes its environment, and how geology and biology are deeply intertwined in the Red Sea.” 

African Wildlife Poop Sheds Light on What Shapes the Gut Ecosystem

Photo Credit: James C. Beasley

A study of elephants, giraffes and other wildlife in Namibia’s Etosha National Park underscores the ways in which the environment, biological sex, and anatomical distinctions can drive variation in the gut microbiomes across plant-eating species. Because the gut microbiome plays a critical role in animal health, the work can be used to inform conservation efforts.

“This study is valuable because Etosha gave us the opportunity to sample such a large number of species under different environmental conditions,” says Erin McKenney, co-author of a paper on the work and an assistant professor of applied ecology at North Carolina State University. “That gives us meaningful insight into the role the environment plays in shaping the gut microbiome of herbivores.

“Unfortunately, this study may also be important for a second reason,” McKenney says. “Etosha is experiencing devastating wildfires affecting a huge section of the park. Because our samples were taken before the wildfires, these findings could inform recovery efforts by helping us understand how species’ microbiomes are adjusting to changes in diet that stem from the fire’s impact on the landscape.”

What Is: Microplastics

Microplastic
Credit: Scientific Frontline

The Invisible Tide of Plastic

The modern era has been defined, in part, by the versatility and ubiquity of plastic. Yet, this celebrated 20th-century material has given rise to a paradoxical form of pollution—one so pervasive and minute that its scale was largely unrecognized until recently. Microplastics, the synthetic dust of our industrial age, represent a global environmental challenge of unprecedented complexity. These tiny particles, born from the fragmentation of larger debris and the intentional design of microscopic products, have infiltrated every corner of the planet. Scientific expeditions have confirmed their presence from the summit of Mount Everest to the abyssal depths of the Mariana Trench. More alarmingly, this invisible tide has crossed the final frontier, entering the human body itself, with researchers detecting microplastic particles in human blood, lung tissue, and even the placenta.

The ubiquity of microplastics signals a fundamental disruption of planetary systems. They are not merely inert debris but active agents in the environment, interacting with ecosystems and organisms in complex and often detrimental ways. Their journey spans the globe, carried by ocean currents, river systems, and atmospheric winds, connecting the most remote wilderness to the most densely populated urban centers in a shared system of contamination. This report provides a definitive, evidence-based synthesis of the current scientific understanding of microplastics. It aims to dissect the full scope of this issue, beginning with a fundamental definition of the pollutant and a detailed accounting of its myriad sources. It will then trace the environmental fate and transport of these particles through aquatic, terrestrial, and atmospheric systems. Finally, the report will conduct an exhaustive analysis of their multifaceted impacts on ecological integrity and human health, concluding with a critical evaluation of the policies, technologies, and strategies required to mitigate this pervasive threat.

Whale poop contains iron that may have helped fertilize past oceans

A blue whale photographed in September 2010.
Photo Credit: NOAA

The blue whale is the largest animal on the planet. It consumes enormous quantities of tiny, shrimp-like animals known as krill to support a body of up to 100 feet (30 meters) long. Blue whales and other baleen whales, which filter seawater through their mouths to feed on small marine life, once teemed in Earth’s oceans. Then over the past century they were hunted almost to extinction for their energy-dense blubber.

As whales were decimated, some thought the krill would proliferate in predator-free waters. But that’s not what happened. Krill populations dropped, too, and neither population has yet recovered.

A recent theory proposes that whales weren’t just predators in the ocean environment. Nutrients that whales excreted may have provided a key fertilizer to these marine ecosystems.

Research led by University of Washington oceanographers supports that theory. It finds that whale excrement contains significant amounts of iron, a vital element that is often scarce in ocean ecosystems, and nontoxic forms of copper, another essential nutrient that in some forms can harm life.

The open-access study, the first to look at the forms of these trace metals in what’s commonly known as whale poop, was published in January in Communications Earth & Environment.

Effects of Declining Diversity Documented in the World of Microbes

Phytoplankton, seen here inside a flask in the Jackrel Lab, are proving to be a valuable system for studying host-associated microbiomes
Photo Credit: Jackrel Lab / UCSD

Across the tree of life, human activities are accelerating declines in biological species diversity, from deserts to oceans to forests. But what about the microscopic world? Scientists in UC San Diego’s School of Biological Sciences recently investigated how declining biodiversity in tiny ecological systems unseen to the naked eye can carry significant consequences for the health of organisms and ecosystems.

Postdoctoral Scholar Jonathan Dickey and recent master’s graduate Nikki Mercer from Assistant Professor Sara Jackrel’s laboratory studied the implications of declining diversity within microbiomes — communities of microorganisms, such as bacteria, which can form tight associations with their hosts, such as plants and animals. Recent studies in microbial ecology have found that microbiomes can play a key role in regulating host health, leading researchers to believe that as our world changes it is imperative to understand the implications of biodiversity loss within the host microbiome.

Cold Waves in the Rainforest: What They Mean for Wild Animals

Typical animals in the lowland rainforest of the Amazon: On the left, the palm-sized dung beetle Coprophanaeus lancifer, which appears to be sensitive to low temperatures. On the right, the Brazilian wandering spider Phoneutria boliviensis, which also grows to the size of a palm. The spider can often be seen at night, but during the cold wave it was nowhere to be seen.
Photo Credit: Kim Lea Holzmann / Universität Würzburg

It's not always cozy and warm in the Amazon rainforest: cold waves can cause temperatures to drop drastically. Würzburg researchers have investigated how animals react to this.

Anyone conducting research in the tropical rainforest does not necessarily have a winter jacket and warm socks with them. After all, this region of the world is considered to have a consistently pleasant temperature. But this is not the case, as Kim Lea Holzmann and Pedro Alonso-Alonso have found out for themselves. Both are doing their doctoral theses at the University of Würzburg's Biocentre and both spent almost the whole of 2023 in the Amazon region in southern Peru to study biodiversity.

It happened on 13 June: a cold spell caused temperatures to plummet from an average of 23.9 to 10.5 degrees Celsius. The cool period lasted almost a week. ‘A year before, we had already experienced a day when it was only 18 degrees,’ says Kim Lea Holzmann. But such severe and prolonged cold seemed strange to them. The local field assistants, on the other hand, were not really surprised. They explained to the Würzburg team that cold spells lasting several days are not that rare in the Amazon.

Drawing a Line from the Gut Microbiome to Inflammation and Depression

Morganella morganii bacteria on a plate.
Photo Credit: Ajay Kumar Chaurasiya
(CC BY-SA 4.0)

It’s become increasingly clear that the gut microbiome can affect human health, including mental health. Which bacterial species influence the development of disease and how they do so, however, is only just starting to be unraveled.

For instance, some studies have found compelling links between one species of gut bacteria, Morganella morganii, and major depressive disorder. But until now no one could tell whether this bacterium somehow helps drive the disorder, the disorder alters the microbiome, or something else is at play.

Harvard Medical School researchers have now pinpointed a biologic mechanism that strengthens the evidence that M. morganii influences brain health and provides a plausible explanation for how it does so.

The findings, published in the Journal of the American Chemical Society, implicate an inflammation-stimulating molecule and offer a new target that could be useful for diagnosing or treating certain cases of the disorder. They also provide a roadmap for probing how other members of the gut microbiome influence human health and behavior.

“There is a story out there linking the gut microbiome with depression, and this study takes it one step further, toward a real understanding of the molecular mechanisms behind the link,” said senior author Jon Clardy, the Christopher T. Walsh, PhD Professor of Biological Chemistry and Molecular Pharmacology in the Blavatnik Institute at HMS.

OHSU researchers use AI machine learning to map hidden molecular interactions in bacteria

Andrew Emili, Ph.D., professor of systems biology and oncological sciences, works in his lab at OHSU. Emili is part of a multi-disciplinary research team that uncovered how small molecules within bacteria interact with proteins, revealing a network of molecular connections that could improve drug discovery and cancer research.
Photo Credit: OHSU/Christine Torres Hicks

A new study from Oregon Health & Science University has uncovered how small molecules within bacteria interact with proteins, revealing a network of molecular connections that could improve drug discovery and cancer research.

The work also highlights how methods and principles learned from bacterial model systems can be applied to human cells, providing insights into how diseases like cancer emerge and how they might be treated. The results are published today in the journal Cell.

The multi-disciplinary research team, led by Andrew Emili, Ph.D., professor of systems biology and oncological sciences in the OHSU School of Medicine and OHSU Knight Cancer Institute, alongside Dima Kozakov, Ph.D., professor at Stony Brook University, studied Escherichia coli, or E. coli, a simple model organism, to map how metabolites — small molecules essential for life — interact with key proteins such as enzymes and transcription factors. These interactions control important processes such as cell growth, division and gene expression, but how exactly they influence protein function is not always clear.

First-of-its-kind integrated dataset enables genes-to-ecosystems research

DOE national laboratory scientists led by Oak Ridge National Laboratory have developed the first tree dataset of its kind, bridging molecular information about the poplar tree microbiome to ecosystem-level processes.
Illustration Credit: Andy Sproles/ORNL, U.S. Dept. of Energy

The first-ever dataset bridging molecular information about the poplar tree microbiome to ecosystem-level processes has been released by a team of Department of Energy scientists led by Oak Ridge National Laboratory. The project aims to inform research regarding how natural systems function, their vulnerability to a changing climate, and ultimately how plants might be engineered for better performance as sources of bioenergy and natural carbon storage.

The data, described in Nature Publishing Group’s Scientific Data, provides in-depth information on 27 genetically distinct variants, or genotypes, of Populus trichocarpa, a poplar tree of interest as a bioenergy crop. The genotypes are among those that the ORNL-led Center for Bioenergy Innovation previously included in a genome-wide association study linking genetic variations to the trees’ physical traits. ORNL researchers collected leaf, soil and root samples from poplar fields in two regions of Oregon — one in a wetter area subject to flooding and the other drier and susceptible to drought. 

Details in the newly integrated dataset range from the trees’ genetic makeup and gene expression to the chemistry of the soil environment, analysis of the microbes that live on and around the trees and compounds the plants and microbes produce.

The dataset “is unprecedented in its size and scope,” said ORNL Corporate Fellow Mitchel Doktycz, section head for Bioimaging and Analytics and project co-lead. “It is of value in answering many different scientific questions.” By mining the data with machine learning and statistical approaches, scientists can better understand how the genetic makeup, physical traits and chemical diversity of Populus relate to processes such as cycling of soil nitrogen and carbon, he said. 

Feeding the lonely brain

Study finds that lonely women experienced increased activation in regions of the brain associated with food cravings
Photo Credit: Ryanwar Hanif

A new UCLA Health study has found that women who perceive themselves to be lonely exhibited activity in regions of the brain associated with cravings and motivation towards eating especially when shown pictures of high calorie foods such as sugary foods. The same group of women also had unhealthy eating behaviors and poor mental health.

Arpana Gupta, Ph.D., a researcher and co-director of the UCLA Goodman-Luskin Microbiome Center, wanted to research the negative impacts of loneliness, especially as people continue to be working remotely after the COVID-19 pandemic, and how the brain interplays with social isolation, eating habits, and mental health. While it is established that obesity is linked to depression and anxiety, and that binge eating is understood to be a coping mechanism against loneliness, Gupta wanted to observe the brain pathways associated with these feelings and behaviors.

“Researching how the brain processes loneliness and how this is related to obesity and health outcomes hasn't been done,” said Gupta, senior author of the paper, which is published in JAMA Network Open. 

The researchers surveyed 93 women about their support system and their feelings of loneliness and isolation, then separated them into two groups: those who scored high on the perceived social isolation scale, and those who scored low. The researchers found that women who had higher levels of social isolation tended to have higher fat mass, lower diet quality, greater cravings, reward-based eating, and uncontrolled eating, and increased levels of anxiety and depression.

Scientists link certain gut bacteria to lower heart disease risk

Rod-shaped Oscillibacter sp. bacteria take up fluorescently labeled cholesterol (here shown in green).
Image Credit: Ahmed Mohamed 

Changes in the gut microbiome have been implicated in a range of diseases including type 2 diabetes, obesity, and inflammatory bowel disease. Now, a team of researchers at the Broad Institute of MIT and Harvard along with Massachusetts General Hospital has found that microbes in the gut may affect cardiovascular disease as well. In a study published in Cell, the team has identified specific species of bacteria that consume cholesterol in the gut and may help lower cholesterol and heart disease risk in people.

Members of Ramnik Xavier’s lab, Broad’s Metabolomics Platform, and collaborators analyzed metabolites and microbial genomes from more than 1,400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for cardiovascular disease. The team discovered that bacteria called Oscillibacter take up and metabolize cholesterol from their surroundings, and that people carrying higher levels of the microbe in their gut had lower levels of cholesterol. They also identified the mechanism the bacteria likely use to break down cholesterol. The results suggest that interventions that manipulate the microbiome in specific ways could one day help decrease cholesterol in people. The findings also lay the groundwork for more targeted investigations of how changes to the microbiome affect health and disease.

“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Xavier, who is a core institute member, director of the Immunology Program, and co-director of the Infectious Disease and Microbiome Program at the Broad. He is also a professor at Harvard Medical School and Massachusetts General Hospital.

Corn reduces arsenic toxicity in soil

Corn plants in a field experiment near Liesberg, Baselland.
Photo Credit: Veronica Caggìa

When crops grow in arsenic-contaminated soil, this toxic element accumulates in the food chain. A study involving the University of Basel has now discovered a mechanism used by corn plants to reduce arsenic uptake: the key factor is a special substance released into the soil by the roots.

Arsenic is a toxic metalloid of natural origin. Arsenic-contaminated soils and waters are found all over the world, especially in southeastern Asian countries like Bangladesh, Vietnam, and China. Also, Switzerland has a few natural hot spots where arsenic is found in above-average concentrations. An example is soil at Liesberg in the canton of Baselland.

“The particular problem for plants is that arsenic behaves chemically similar to phosphorus,” says Professor Klaus Schlaeppi of the Department of Environmental Sciences at the University of Basel. Phosphorus is an important nutrient that plants take up through special transport channels in their roots. “The arsenic enters the plants through these channels.” As a result, more and more of the toxic substance accumulates in the biomass and gets into the food chain. On the long run, this negatively affects human health. High arsenic exposure can cause neurological damage and cancer, for example.

Researchers Identify Microbes That Help Plants Thwart Parasite

Sorghum crops in sub-Saharan Africa suffer heavy losses from the parasitic plant witchweed (Striga hermonthica). A new study shows how soil microbes can help protect sorghum from this pest and could be the basis for a soil probiotic treatment.
Photo Credit: Sabine

Bacteria that could help one of Africa’s staple crops resist a major pest have been identified by researchers at the University of California, Davis. Their findings, published in Cell Reports, could improve yields of sorghum, a mainstay of food and drink in West and East African countries.

About 20 percent of Africa’s sorghum crop is lost due to witchweed (Striga hermonthica), a parasitic plant that steals nutrients and water by latching onto the plant’s roots.

In a new study, UC Davis researchers show that soil microbes induce changes in sorghum roots that make the plant more resistant to infection by witchweed. They identified specific strains of bacteria that trigger these resistance traits and could be applied as a soil “probiotic” to improve sorghum yields in future.

“These microbes have great promise as soil additives that can help farmers grow sorghum successfully in sub-Saharan Africa,” said Siobhan Brady, a professor in the Department of Plant Biology and Genome Center and a senior author on the paper. 

Gut microbiota and antibiotics: Missing puzzle piece discovered

3D model of the small ribonucleic acid MasB.
Image Credit: Alexander Westermann/HIRI

HIRI scientists have identified a small RNA that influences the sensitivity of the intestinal commensal Bacteroides thetaiotaomicron to certain antibiotics.

The intricacies of how intestinal bacteria adapt to their environment have yet to be fully explored. Researchers from the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg and the University of California, Berkeley, USA, have now successfully closed a gap in this knowledge: They have identified a small ribonucleic acid (sRNA) that affects the susceptibility of the gut commensal Bacteroides thetaiotaomicron to specific antibiotics. The findings, published today in the journal Nature Microbiology, could serve as the foundation for novel therapies addressing intestinal diseases and combating antibiotic resistance. 

The gut, a complex ecosystem of numerous microorganisms, plays a pivotal role in human well-being. Factors like dietary changes, medications, or bile salts can influence the microbiota, impacting health. Among the prevalent intestinal bacteria in humans are Bacteroides thetaiotaomicron. These gut microbes play a role in breaking down polysaccharides during digestion, contributing to human health. Yet they can also promote infections when the ecosystem is disbalanced, such as after antibiotic treatment. However, the molecular mechanisms enabling these gut microbes to adapt to their environment remain largely unknown.

Maternal obesity may promote liver cancer

Obese mice pass on an altered microbiome to their offspring, which has an impact on liver health in adulthood and increases the risk of liver cancer. Normalising the intestinal microbiome reduces the risk of cancer. Specific families of bacteria are linked to tumour burden and liver inflammation.
Image Credit: Toso, Moeckli et al. 2024
CC-by-nc-nd

A team from the UNIGE and the HUG has revealed the role of the microbiota in the increased risk of developing liver disease in the offspring of mothers suffering from obesity.

Obesity, which could reach 50% of the population in certain developed countries by 2030, is a major public health concern. It not only affects the health of those who suffer from it, but could also have serious consequences for their offspring. Scientists at the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG) have studied the impact of maternal obesity on the risk of developing liver disease and liver cancer. Using an animal model, the team discovered that this risk was indeed much higher in the offspring of mothers suffering from obesity. One of the main causes was the transmission of a disturbed intestinal microbiota from the mother, resulting in a chronic liver disease whose effects became apparent in adulthood. These results, which have yet to be confirmed in humans, are a warning signal and a call for action to limit the deleterious effect of obesity on children. This research is published in the journal JHEP Reports.

“Molecular Rosetta Stone” Reveals How our Microbiome Talks to Us

Bacteria in the gut convert bile acids produced by the liver into a wide array of new compounds. These molecules are akin to the language of the gut microbiome, allowing them to influence distant organ systems.
Photo Credit: Lakshmiraman Oza

Researchers from Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California San Diego have uncovered thousands of previously unknown bile acids, a type of molecule used by our gut microbiome to communicate with the rest of the body.

“Bile acids are a key component of the language of the gut microbiome, and finding this many new types radically expands our vocabulary for understanding what our gut microbes do and how they do it,” said senior author Pieter Dorrestein, Ph.D., professor at Skaggs School of Pharmacy and Pharmaceutical Sciences and professor of pharmacology and pediatrics at UC San Diego School of Medicine. “It’s like going from ‘See Spot Run’ to Shakespeare.”

The results, as described by study co-author and bile acids expert Lee Hagey, Ph.D, are akin to a molecular Rosetta stone, providing previously unknown insight into the biochemical language microbes use to influence distant organ systems.

Research reveals new insights into marine plastic pollution

Photo Credit: Lucien Wanda

A groundbreaking study led by researchers at the University of Stirling has uncovered the crucial role of bacteria living on plastic debris.

The research also identifies rare and understudied bacteria that could assist in plastic biodegradation, offering new insights for tackling plastic pollution.

Plastic pollution is a worldwide problem, with up to two million tons estimated to enter oceans every year, damaging wildlife and ecosystems.

In a pioneering study, experts at the University of Stirling’s Faculty of Natural Sciences and the University of Mons (Belgium) analyzed the proteins in plastic samples taken from Gullane Beach in Scotland.

Unlike previous studies carried out in warmer climates that focus on the genetic potential of biofilms inhabiting plastics, this research led by Dr Sabine Matallana-Surget took a unique approach by analyzing the proteins expressed by active microorganisms.

Their findings have unveiled a remarkable discovery of enzymes actively engaged in degrading plastic. Moreover, the team has pioneered new methodologies for enhanced predictions in marine microbiology research.