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• 'Noisy' Roundworm Brains Give Rise to Individuality
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• Even Inactive Smokers Are Densely Colonized by Microbial Communities
• Protein Fragments ID Two New 'extremophile' Microbes--and May Help Find Alien Life
• Gut Bacteria Important for Overcoming Milk Allergy

Thursday, March 14, 2024

• Infections from These Bacteria Are on the Rise: New Blood Test Cuts Diagnosis Time from Months to Hours
• New Study on Mating Behaviors Offers Clues Into the Evolution of Attraction
• Dog-Killing Flatworm Discovered in Southern California
• It's Hearty, It's Meaty, It's Mold
• Alzheimer's Drug Fermented With Help from AI and Bacteria Moves Closer to Reality
• New Bioengineered Protein Design Shows Promise in Fighting COVID-19
• New Simpler and Cost-Effective Forensics Test Helps Identify Touch DNA

Wednesday, March 13, 2024

• Sulfur and the Origin of Life
• Tryptophan in Diet, Gut Bacteria Protect Against E. Coli Infection
• Study Shows Important Role Gut Microbes Play in Airway Health in Persons With Cystic Fibrosis
• Steroid Drugs Used for HRT Can Combat E. Coli and MRSA
• Simple Trick Could Improve Accuracy of Plant Genetics Research
• Milk to the Rescue for Diabetics? Cow Produces Human Insulin in Milk
• Who Knew That Coprophagy Was So Vital for Birds' Survival?

Tuesday, March 12, 2024

• A Simple and Robust Experimental Process for Protein Engineering
• Scientists Find Weak Points on Epstein-Barr Virus
• Maternal Obesity May Promote Liver Cancer

Monday, March 11, 2024

• Researchers Uncover Protein Responsible for Cold Sensation
• Higher Bacterial Counts Detected in Single-Serving Milks, Researchers Report

Friday, March 8, 2024

• New Study Discovers How Altered Protein Folding Drives Multicellular Evolution
• Researchers Develop Artificial Building Blocks of Life
• Researchers Open New Leads in Anti-HIV Drug Development, Using a Compound Found in Nature

Thursday, March 7, 2024

• How Does a Virus Hijack Insect Sperm to Control Disease Vectors and Pests?
• The Malaria Parasite Generates Genetic Diversity Using an Evolutionary 'copy-Paste' Tactic
• What Makes a Pathogen Antibiotic-Resistant?
• First Atom-Level Structure of Packaged Viral Genome Reveals New Properties, Dynamics
• Cracking Epigenetic Inheritance: Biologists Discovered the Secrets of How Gene Traits Are Passed on

Wednesday, March 6, 2024

• Revealing a Hidden Threat: Researchers Show Viral Infections Pose Early Heart Risks
• Microbes Impact Coral Bleaching Susceptibility
• Early Life Adversity Leaves Long-Term Signatures in Baboon DNA
• Revealing the Evolutionary Origin of Genomic Imprinting
• Universal Tool for Tracking Cell-to-Cell Interactions
• Synthetic Gene Helps Explain the Mysteries of Transcription Across Species
• Decoding the Language of Epigenetic Modifications
• Deconstructing the Structural Elements of a Lesser-Known Microbe

Tuesday, March 5, 2024

• Lab-Grown Liver Organoid to Speed Up Turtle Research, Making Useful Traits Easier to Harness
• Possible 'Trojan Horse' Found for Treating Stubborn Bacterial Infections
• Microalgae With Unusual Cell Biology

Monday, March 4, 2024

• Protecting Joints from Bacteria With Mussels
• Modeling the Origins of Life: New Evidence for an 'RNA World'
• An Evolutionary Mystery 125 Million Years in the Making
• Photosynthetic Secrets Come to Light
• Advances in Forensic Science Improve Accuracy of 'time of Death' Estimates

Friday, March 1, 2024

• Researchers Create Coating Solution for Safer Food Storage
• Light Into the Darkness of Photosynthesis
• How Virus Causes Cancer: Potential Treatment

Thursday, February 29, 2024

• New Role for Bacterial Enzyme in Gut Metabolism Revealed
• Refrigerate Lettuce to Reduce Risk of E. Coli Contamination
• Microbial Viruses Act as Secret Drivers of Climate Change
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• Scientists Develop Novel RNA Or DNA-Based Substances to Protect Plants from Viruses
• Radio Waves Can Tune Up Bacteria to Become Life-Saving Medicines
• Scientists Discover 18 New Species of Gut Microbes in Search for Origins of Antibiotic Resistance

Wednesday, February 28, 2024

• Study Reveals Accelerated Soil Priming Under Climate Warming
• New Tool Helps Decipher Gene Behavior
• In Fight Against Brain Pathogens, the Eyes Have It
• Double Trouble at Chromosome Ends
• Change in Gene Code May Explain How Human Ancestors Lost Tails

Tuesday, February 27, 2024

• New Discovery Shows How Cells Defend Themselves During Stressful Situations
• Microbial Comics: RNA as a Common Language, Presented in Extracellular Speech-Bubbles
• Low-Temperature Plasma Used to Remove E. Coli from Hydroponically Grown Crops

Monday, February 26, 2024

• 'Janitors' Of the Sea: Overharvested Sea Cucumbers Play Crucial Role in Protecting Coral
• Cutting-Edge 'protein Lawnmower' Created
• Scientists Assemble a Richer Picture of the Plight and Resilience of the Foothill Yellow-Legged Frog
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Sunday, February 25, 2024

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Friday, February 23, 2024

• Altering the Circadian Clock Adapts Barley to Short Growing Seasons
• Lab-Spun Sponges Form Perfect Scaffolds for Growing Skin Cells to Heal Wounds

Thursday, February 22, 2024

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Microbiology

Viral Genetics Confirms What On-the-Ground Activists Knew Early in the Mpox Outbreak

Molecular biology could have changed the mpox epidemic—and could stop future outbreaks

Joseph Osmundson

Cannibal Cells Inspire Cancer Treatment Improvement

Giving cells an appetite for cancer could enhance treatments

Kate Graham-Shaw

Is Raw-Milk Cheese Safe to Eat?

Recent bacterial outbreaks from consuming cheese made from unpasteurized milk, or “raw milk,” raise questions about the safety of eating these artisanal products

Riis Williams

Many Pregnancy Losses Are Caused by Errors in Cell Division

Odd cell divisions could help explain why even young, healthy couples might struggle to get pregnant

Gina Jiménez

'Microbiome of Death' Uncovered on Decomposing Corpses Could Aid Forensics

Microbes that lurk in decomposing human corpses could help forensic detectives establish a person's time of death

Christoph Schwaiger, LiveScience

Weird ‘Obelisks’ Found in Human Gut May be Virus-Like Entities

Rod-shaped fragments of RNA called “obelisks” were discovered in gut and mouth bacteria for the first time

Joanna Thompson

Semen Has Its Own Microbiome—And It Might Influence Fertility

Recent research found a species of bacteria living in semen that’s associated with infertility and has links to the vaginal microbiome

Andrew Chapman

Bacteria Make Decisions Based on Generational Memories

Bacteria choose to swarm based on what happened to their great-grandparents

Allison Parshall

Your Body Has Its Own Built-In Ozempic

Popular weight-loss and diabetes drugs, such as Ozempic and Wegovy, target metabolic pathways that gut microbes and food molecules already play a key role in regulating

Christopher Damman, The Conversation US

See Your Body’s Cells in Size and Number

The larger a cell type is, the rarer it is in the body—and vice versa—a new study shows

Clara Moskowitz, Jen Christiansen, Ni-ka Ford

Subterranean ‘Microbial Dark Matter’ Reveals a Strange Dichotomy

The genes of microbes living as deep as 1.5 kilometers below the surface reveal a split between minimalist and maximalist lifestyles

Stephanie Pappas

The Vaginal Microbiome May Affect Health More than We Thought

A recent study finds varying combinations of microbes in the vaginal microbiome may influence health outcomes such as risk of sexually transmitted disease and preterm birth

Lori Youmshajekian

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Turning microbiome research into a force for health

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The microbiome comprises trillions of microorganisms living on and inside each of us. Historically, researchers have only guessed at its role in human health, but in the last decade or so, genetic sequencing techniques have illuminated this galaxy of microorganisms enough to study in detail.

As researchers unravel the complex interplay between our bodies and microbiomes, they are beginning to appreciate the full scope of the field’s potential for treating disease and promoting health.

For instance, the growing list of conditions that correspond with changes in the microbes of our gut includes type 2 diabetes, inflammatory bowel disease, Alzheimer’s disease, and a variety of cancers.

“In almost every disease context that’s been investigated, we’ve found different types of microbial communities, divergent between healthy and sick patients,” says professor of biological engineering Eric Alm. “The promise [of these findings] is that some of those differences are going to be causal, and intervening to change the microbiome is going to help treat some of these diseases.”

Alm’s lab, in conjunction with collaborators at the Broad Institute of MIT and Harvard, did some of the early work characterizing the gut microbiome and showing its relationship to human health. Since then, microbiome research has exploded, pulling in researchers from far-flung fields and setting new discoveries in motion. Startups are now working to develop microbiome-based therapies, and nonprofit organizations have also sprouted up to ensure these basic scientific advances turn into treatments that benefit the maximum number of people.

 “The first chapter in this field, and our history, has been validating this modality,” says Mark Smith PhD ’14, a co-founder of OpenBiome, which processes stool donations for hospitals to conduct stool transplants for patients battling gut infection. Smith is also currently CEO of the startup Finch Therapeutics, which is developing microbiome-based treatments. “Until now, it’s been about the promise of the microbiome. Now I feel like we’ve delivered on the first promise. The next step is figuring out how big this gets.”

An interdisciplinary foundation

MIT’s prominent role in microbiome research came, in part, through its leadership in a field that may at first seem unrelated. For decades, MIT has made important contributions to microbial ecology, led by work in the Parsons Laboratory in the Department of Civil and Environmental Engineering and by scientists including Institute Professor Penny Chisholm.

Ecologists who use complex statistical techniques to study the relationships between organisms in different ecosystems are well-equipped to study the behavior of different bacterial strains in the microbiome.

Not that ecologists — or anyone else — initially had much to study involving the human microbiome, which was essentially a black box to researchers well into the 2000s. But the Human Genome Project led to faster, cheaper ways to sequence genes at scale, and a group of researchers including Alm and visiting professor Martin Polz began using those techniques to decode the genomes of environmental bacteria around 2008.

Those techniques were first pointed at the bacteria in the gut microbiome as part of the Human Microbiome Project, which began in 2007 and involved research groups from MIT and the Broad Institute.

Alm first got pulled into microbiome research by the late biological engineering professor David Schauer as part of a research project with Boston Children’s Hospital. It didn’t take much to get up to speed: Alm says the number of papers explicitly referencing the microbiome at the time could be read in an afternoon.

The collaboration, which included Ramnik Xavier, a core institute member of the Broad Institute, led to the first large-scale genome sequencing of the gut microbiome to diagnose inflammatory bowel disease. The research was funded, in part, by the Neil and Anna Rasmussen Family Foundation.

The study offered a glimpse into the microbiome’s diagnostic potential. It also underscored the need to bring together researchers from diverse fields to dig deeper.

Taking an interdisciplinary approach is important because, after next-generation sequencing techniques are applied to the microbiome, a large amount of computational biology and statistical methods are still needed to interpret the resulting data — the microbiome, after all, contains more genes than the human genome. One catalyst for early microbiome collaboration was the Microbiology Graduate PhD Program, which recruited microbiology students to MIT and introduced them to research groups across the Institute.

As microbiology collaborations increased among researchers from different department and labs, Neil Rasmussen, a longtime member of the MIT Corporation and a member of the visiting committees for a number of departments, realized there was still one more component needed to turn microbiome research into a force for human health.

“Neil had the idea to find all the clinical researchers in the [Boston] area studying diseases associated with the microbiome and pair them up with people like [biological engineers, mathematicians, and ecologists] at MIT who might not know anything about inflammatory bowel disease or microbiomes but had the expertise necessary to solve big problems in the field,” Alm says.

In 2014, that insight led the Rasmussen Foundation to support the creation of the Center for Microbiome Informatics and Therapeutics (CMIT), one of the first university-based microbiome research centers in the country. CMIT is based at the MIT Institute for Medical Engineering and Science (IMES).

Tami Lieberman, the Hermann L. F. von Helmholtz Career Development Professor at MIT, whose background is in ecology, says CMIT was a big reason she joined MIT’s faculty in 2018. Lieberman has developed new genomic approaches to study how bacteria mutate in healthy and sick individuals, with a particular focus on the skin microbiome.

Laura Kiessling, a chemist who has been recognized for contributions to our understanding of cell surface interactions, was also quick to join CMIT. Kiessling, the Novartis Professor of Chemistry, has made discoveries relating to microbial mechanisms that influence immune function. Both Lieberman and Kiessling are also members of the Broad Institute.

Today, CMIT, co-directed by Alm and Xavier, facilitates collaborations between researchers and clinicians from hospitals around the country in addition to supporting research groups in the area. That work has led to hundreds of ongoing clinical trials that promise to further elucidate the microbiome’s connection to a broad range of diseases.

Fulfilling the promise of the microbiome

Researchers don’t yet know what specific strains of bacteria can improve the health of people with microbiome-associated diseases. But they do know that fecal matter transplants, which carry the full spectrum of gut bacteria from a healthy donor, can help patients suffering from certain diseases.

The nonprofit organization OpenBiome, founded by a group from MIT including Smith and Alm, launched in 2012 to help expand access to fecal matter transplants by screening donors for stool collection then processing, storing, and shipping samples to hospitals. Today OpenBiome works with more than 1,000 hospitals, and its success in the early days of the field shows that basic microbiome research, when paired with clinical trials like those happening at CMIT, can quickly lead to new treatments.

“You start with a disease, and if there’s a microbiome association, you can start a small trial to see if fecal transplants can help patients right away,” Alm explains. “If that becomes an effective treatment, while you’re rolling it out you can be doing the genomics to figure out how to make it better. So you can translate therapeutics into patients more quickly than when you’re developing small-molecule drugs.”

Another nonprofit project launched out of MIT, the Global Microbiome Conservancy, is collecting stool samples from people living nonindustrialized lifestyles around the world, whose guts have much different bacterial makeups and thus hold potential for advancing our understanding of host-microbiome interactions.

A number of private companies founded by MIT alumni are also trying to harness individual microbes to create new treatments, including, among others, Finch Therapeutics founded by Mark Smith; Concerto Biosciences, co-founded by Jared Kehe PhD ’20 and Bernardo Cervantes PhD ’20; BiomX, founded by Associate Professor Tim Lu; and Synlogic, founded by Lu and Jim Collins, the Termeer Professor of Medical Engineering and Science at MIT.

“There’s an opportunity to more precisely change a microbiome,” explains CMIT’s Lieberman. “But there’s a lot of basic science to do to figure out how to tweak the microbiome in a targeted way. Once we figure out how to do that, the therapeutic potential of the microbiome is quite limitless.”

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• Published: 05 October 2020

Microbes and microbiomes in 2020 and beyond

• Aravind Natarajan   ORCID: orcid.org/0000-0003-2180-7842 1 , 2 &
• Ami S. Bhatt   ORCID: orcid.org/0000-0001-8099-2975 1 , 2  

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• Metagenomics

In the next decade, advances in our understanding of microbes and microbiomes will likely transform our way of life; providing novel therapeutics, alternate energy sources, and shaping fundamental doctrines of biology. We explore the promises herein, and tools required to achieve this progress. Notably, it is critical that we improve the inclusivity and diversity of our research agendas and teams, so that science benefits people of all identities and backgrounds.

Microbes have shaped the course of humanity, enabling basic biological discoveries such as the triplet nature of codons, yielding therapeutics including numerous antibiotics, and contributing to everyday life by serving us fermented products and as sources of enzymes for our laundry detergent. Recent studies have also revealed that our healthy existence is intricately reliant on microbes that inhabit our body and influence physiological functions in ways that we are only beginning to understand. Notably, the entirety of our knowledge of and from microbes is derived from 0.001% of microbial taxa predicted to exist on earth 1 . With advances in technology that enable us to investigate microbes across time and space, humanity has the opportunity ‘ to explore strange new worlds. To seek out new life and new civilizations. To boldly go where no one has gone before!’ guided by reams of sequence information. In this commentary, we reflect on the impact of the burgeoning knowledge of microbes and microbiomes, and some of the tools required to explore this new world.

Human microbiome

The study of the human microbiome takes us back to the origins of microbiology when Antonie van Leeuwenhoek invented the simple microscope and first saw bacteria (which he termed animalcules ) derived from pond scum and between his teeth. Through concerted efforts over the last two decades, we now better understand the identity of microbes that inhabit the human body. In certain cases, we even understand the roles of specific microbes in the maintenance of our health. Despite some promising advances, the holy grail of microbe-based therapeutics has under-delivered, perhaps because of premature hype from associative knowledge and absence of causative information. However, as we move past the first wave of exploratory enthusiasm, the field is making rapid progress, developing computational algorithms, genetic tools for microbial manipulation, improved metrics for measurements, and high-throughput experiments to nail down molecular and biochemical details of the complex relationship between human hosts and microbes. We anticipate that understanding the intricate signaling between microbes, and with the host 2 , 3 through small molecules and peptides will be a key area of progress that will yield therapeutics and clinical interventions. Further, sequencing technologies and bioinformatic algorithms that are honed to characterize phages, protists and other eukaryotic symbionts of the human body are promising areas of development. Despite the wave of new information that is being generated, one area of concern in studies on the human microbiome is the lack of diversity in research subjects, where most studies focus on western and Caucasian populations. We need to urgently act to ensure that existing disparities in healthcare are not exacerbated as we make forays into new therapeutic avenues backed by our knowledge of the human microbiome 4 .

Environmental microbiome

In the past decade, we have witnessed fascinating advances in the study of microbes from diverse ecologies, including intricate symbionts at submarine volcanic eruptions 5 , hardy survivors in the Atacama desert (ecology akin to Mars) 6 , and ‘huge phages’ found in wide-ranging ecosystems 7 . Focused efforts like the Tara Expeditions and Earth Microbiome project 8 that leverage massive sampling in combination with high-throughput sequencing have significantly expanded the catalog of known microbes. While these endeavors are invaluable in advancing our knowledge, it is humbling to remember that despite our best efforts, we are still only sampling a miniscule fraction of the 10 12 microbial species predicted to currently exist 1 , and an even smaller fraction of the organisms that have ever existed and will exist in the future. In the new decade, we anticipate learning new facets of the rules of life and biocatalyzed chemistries from these novel microorganisms. For instance, strategies to assemble complete genomes 9 , 10 , 11 , track mobile genetic elements 12 and extrachromosomal elements 13 may finally allow us to comprehensively grasp the dynamics of the evolution and exchange of genetic material. This will also provide us insight into novel classes of enzymes that interact with nucleic acids in fundamental processes such as DNA repair, epigenetic modifications, and recombination, and have translational utility in genome engineering, just as CRISPR/Cas systems have revolutionized molecular biology. While modern tools and techniques have allowed us to explore new organisms, we are also improving our understanding of well-studied model organisms like Escherichia coli . For instance, advances in biochemical, computational and microscopy-based techniques have enabled us to dissect the nature and extent of subcellular organization in this familiar microbe, yielding exciting new fundamental insights.

Transformative tools and technology

The biggest challenge in honing tools to explore the unknown remains our deep familiarity with the known. Therefore, we need to constantly remember that our world view of microbes and their potential is based on a fraction of the existent diversity of life. One strategy to develop enabling futuristic tools is to remain unfettered by current biological principles, and lean on the fundamental sciences of mathematics, physics and chemistry, and contemporaneous machine learning algorithms. Mathematical frameworks that can handle the inherent nonlinearity, stochasticity and complexity of biological problems, assembling multi-omics data at a systems level, are a cornerstone for progress. Similarly, defining statistical measures that are most relevant to assessing ecological interactions is also invaluable to capture signal over noisy data with reasonable sensitivity. Cutting edge physics has pushed the boundaries of microscopy, down to even visualizing folded proteins 14 and RNAs 15 . In the next decade, we anticipate non-invasive methods to capture host-microbe and other systems level interactions in vivo. An important element herein is advancements in robust fluorescence markers and strategies in bioorthogonal chemistry that can identify and label different biomolecules such as nucleic acids, cell-surface proteins, and sugars. Peering within a cell, improvements in mass spectrometry, pushing the boundaries of physicochemical principles, have enabled researchers to gain metabolic insights that were previously inaccessible. We hope that such high-throughput strategies in analytical chemistry continue to advance, enabling identification of small molecules ab initio from complex mixtures. These efforts in metabolomics will benefit from innovative bioinformatic algorithms that identify and predict functional pathways in microbes. Similar computational efforts to map the metabolic potential and growth requirements of traditionally unculturable microbes will augment our ability to grow these exotic bugs and understand their biology. Finally, computer algorithms have exponentially transformed the scale of biological investigations, ranging from massive efforts to identify novel microbes, to characterizing molecular pathways, and defining fundamental principles of biochemical and molecular interactions. Further, maturation of machine learning strategies will enable us to take a fresh approach to data analysis, uncluttered by limitations of the human imagination.

Taken together, in the centuries since the time of van Leeuwenhoek, breakthrough discoveries have exemplified the transformative power of discovering new microbes, understanding their biology, and gaining access to their evolutionarily honed biocatalytic potential. Recognizing that this is just a tiny fraction of the abounding knowledge and resources that exist around us inspires curiosity and verve that in turn fosters endeavors in research. These efforts will certainly improve the quality of our lives and likely even sustain our survival as a species. The steady rise in multi-drug resistant superbugs and extended dry spell in the discovery of novel antibiotics is a major cause for concern. We hope that microbes will continue to yield novel antibiotics and inspire new synthetic solutions. Further, as we make progress in deciphering  the mechanisms that commensal microbes use to influence its human host, we are certain to see a new wave of microbe-based therapeutics, including the potential use of bugs or “bug-derived products” as drugs. The promising impacts of new frontiers in microbiome research extend well beyond medicine. This has never been more evident as we rely on microbial cellulases for the production of biofuels, and realize that microbes are the largest players in the global carbon cycle with a tangible impact on global warming and the health of our planet. At a more fundamental level, we are innately curious about how the world around us works and the delightfully different manifestations of life. While it is certain that the next decade of microbiome research will reveal novel strategies in survival, unimagined metabolic pathways and intricate mechanisms in genetic regulation, it may well challenge more sacrosanct principles such as the central dogma. For instance, microbes did present us nonribosomal peptide synthesis as an alternate route to protein expression.

Finally, as we look ahead and chart the course for our exciting explorations of microbes and microbiomes, it is imperative to take stock of who is privileged to participate in this journey and who reaps the most benefits from its bounties. Scientists of underrepresented identities continue to face systemic challenges that preclude them from fully engaging in research. Further, therapeutics by and large are neither developed for nor tested in diverse populations. The racial, ethnic and socioeconomic inequality in subjects of human microbiome research threatens to perpetuate this disparity in healthcare. While it is beyond the scope of this commentary to deeply assess this problem or to offer solutions, we believe that as we look to the future, it is imperative not only to focus on what we see through the microscope but also to be keenly aware of the context of our work in the broader society.

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Acknowledgements

We are thankful to our many colleagues—those in our lab, in the larger Stanford “Bug Club” community, and around the world—for their groundbreaking work and collegiality. Their ongoing contributions and commitment to open science have enabled the field of microbiome research to advance at an impressive pace. We also acknowledge funding support from the following sources: NIH R01 AI143757, NIH R01 AI148623, the V Foundation, and the Sloan Foundation.

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Aravind Natarajan & Ami S. Bhatt

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A.N. and A.S.B. contributed equally to all aspects of this article.

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A.N. has no competing interests. A.S.B. is on the advisory board of January.ai, Caribou Biosciences, and ArcBio, and has served as a paid consultant for BiomX and Guardant Health.

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Natarajan, A., Bhatt, A.S. Microbes and microbiomes in 2020 and beyond. Nat Commun 11 , 4988 (2020). https://doi.org/10.1038/s41467-020-18850-6

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Received : 24 August 2020

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DOI : https://doi.org/10.1038/s41467-020-18850-6

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