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The cFMD – curatedFoodMetagenomicData database – What’s in the microbiome of the foods we eat?
Microbes are part of the food we eat and can influence our own microbiome, but we know very little about the microbes in our foods. Now, researchers have developed a database of the “food microbiome” by sequencing the metagenomes of 2,533 different foods. They identified 10,899 food-associated microbes, half of which were previously unknown species, and showed that food-associated microbes account for around 3% of the adult and 56% of the infant gut microbiome on average. The study published August 29 in the journal Cell, and the database is available as an open access resource.

“This is the largest survey of microbes in food,” says co-senior author and computational microbiologist Nicola Segata (@nsegata) of the University of Trento and the European Institute of Oncology in Milan. “We can now start to use this reference to better understand how the quality, conservation, safety, and other characteristics of food are linked with the microbes they contain.”

Traditionally, microbes in food have been studied by culturing them one-by-one in the lab, but this process is slow and time consuming, and not all microbes can be easily cultured. To characterize the food microbiome more comprehensively and efficiently, the researchers leveraged metagenomics, a molecular tool that enabled them to simultaneously sequence all the genetic material within each food sample. Metagenomics is often used to characterize the human microbiome or analyze environmental samples but hasn’t previously been used to investigate food at a large scale.

“Food microbiologists have been studying foods and testing for food safety for well over a hundred years now, but we’ve underutilized modern DNA sequencing technologies,” says co-senior author and microbiologist Paul Cotter (@pauldcotter) of Teagasc, APC Microbiome Ireland and VistaMilk Ireland. “This is the starting point for a new wave of studies in the field where we make full use of the molecular technology available.”

Altogether, the team analyzed 2,533 food-associated metagenomes from 50 countries, including 1,950 newly sequenced metagenomes. These metagenomes came from a variety of food types, of which 65% were dairy sources, 17% were fermented beverages, and 5% were fermented meats.

These metagenomes comprised genetic material from 10,899 food-associated microbes categorized into 1,036 bacterial and 108 fungal species. Similar foods tended to harbor similar types of microbes—for example, the microbial communities in different fermented beverages were more similar to each other than to the microbes in fermented meat—but there was more variation between dairy products, likely due to the larger number of dairy products surveyed.

Though the researchers didn’t identify many overtly pathogenic bacteria in the food samples, they did identify some microbes that might be less desirable due to their impact on food flavor or preservation. Knowing which microbes “belong” in different types of food could help producers—both industrial and small-scale—to produce more consistent and desirable products. It could also help food regulators define which microbes should and should not be in certain types of food and to authenticate the identity and origins of “local” foods.

“One thing that was striking is that some microbes are present and performing similar functions in even quite different foods, and at the same time, we showed that foods in each local facility or farm have unique characteristics,” says Segata. “This is important because it could further improve the idea of the specificity and the quality of local foods, and we could even use metagenomics to authenticate foods coming from a given facility or location.”

Understanding the food microbiome could also have implications for human health as some of the microbes we eat could become stable members of our own microbiomes. To examine overlaps between food-associated microbes and the human microbiome, the team compared their new database with 19,833 previously sequenced human metagenomes. They showed that food-associated microbial species compose around 3% of the gut microbiome of adults and more than 50% of the gut microbiomes of newborns.

“This suggests that some of our gut microbes may be acquired directly from food, or that historically, human populations got these microbes from food and then those microbes adapted to become part of the human microbiome,” says Segata. “It might seem like only a small percentage, but that 3% can be extremely relevant for their function within our body. With this database, we can start surveying at a large scale how the microbial properties of food could impact our health.”

The study was one of the main outputs from the MASTER EU consortium, an EU-funded initiative spanning 29 partners across 14 countries that aims to characterize the presence and function of microbes throughout the entire food chain.

“In the future, we want to explore the diversity of these food microbiomes with respect to different foods, cultures, lifestyles, and populations,” says Cotter.

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This research was supported by Horizon 2020 of Horizon Europe, the Italian Ministry of Foreign Affairs and International Cooperation, the European Research Council, the National Cancer Institute of the National Institutes of Health, the Spanish Ministry of Science and Innovation, the Science Foundation Ireland, and the Irish Department of Agriculture, Food and the Marine.

 

Bibliographic information:

Carlino et al., “Unexplored microbial diversity from 2,500 food metagenomes and links with the human microbiome”, Cell, DOI: 10.1016/j.cell.2024.07.039

The cFMD - curatedFoodMetagenomicData database

Press release from Cell Press.

Plants emit sounds, especially when they are stressed

For the first time in the world, Tel Aviv University researchers recorded and analyzed sounds distinctly emitted by plants.

Left to right: Prof. Yossi Yovel & Prof. Lilach Hadany. Credits: Tel Aviv University, CC BY

Do you talk to your plants? While you may not be able to hear them, your plants could very well be chatting away as well (perhaps they are not such great listeners after all), and that’s especially true if they are having a bad day (did you forget to water them again?). For the first time in the world, TAU researchers recorded and analyzed sounds distinctly emitted by plants. The click-like sounds, resembling the popping of popcorn, are emitted at a volume similar to human speech, but at high frequencies, beyond the hearing range of the human ear. The researchers:

“We found that plants usually emit sounds when they are under stress, and that each plant and each type of stress is associated with a specific identifiable sound. While imperceptible to the human ear, the sounds emitted by plants can probably be heard by various animals, such as bats, mice, and insects.”

plants sounds
Cactus plant with Microphones. Credits: Tel Aviv University, CC BY

Resolving Old Scientific Controversy

The study was led by Prof. Lilach Hadany from the School of Plant Sciences and Food Security at The George S. Wise Faculty of Life Sciences, together with Prof. Yossi Yovel, Head of the Sagol School of Neuroscience and faculty member at the School of Zoology and the Steinhardt Museum of Natural History, and research students Itzhak Khait and Ohad Lewin-Epstein, in collaboration with researchers from the Raymond and Beverly Sackler School of Mathematical Sciences, the Institute for Cereal Crops Research, and the Sagol School of Neuroscience – all at Tel Aviv University. The paper was published in the prestigious scientific journal Cell.

“From previous studies we know that vibrometers attached to plants record vibrations,” says Prof. Hadany. “But do these vibrations also become airborne soundwaves – sounds that can be recorded from a distance? Our study addressed this question, which researchers have been debating for many years.”

At the first stage of the study the researchers placed plants in an acoustic box in a quiet, isolated basement with no background noise. Ultrasonic microphones recording sounds at frequencies of 20-250 kilohertz (the maximum frequency detected by a human adult is about 16 kilohertz) were set up at a distance of about 10cm from each plant. The study focused mainly on tomato and tobacco plants, but wheat, corn, cactus and henbit were also recorded.

plants sounds
Prof. Lilach Hadany. Credits: Tel Aviv University, CC BY

Mapping Plants’ Complaints with AI

Before placing the plants in the acoustic box, the researchers subjected them to various treatments: some plants had not been watered for five days, in some the stem had been cut, and some were untouched. Prof. Hadany explains that their intention was to test whether the plants emit sounds, and whether these sounds are affected in any way by the plant’s condition:

“Our recordings indicated that the plants in our experiment emitted sounds at frequencies of 40-80 kilohertz. Unstressed plants emitted less than one sound per hour, on average, while the stressed plants – both dehydrated and injured – emitted dozens of sounds every hour.”

plants sounds
Eavesdropping on a cut plant. Credits: Tel Aviv University, CC BY

The recordings collected in this way were analyzed by specially developed machine learning (AI) algorithms. The algorithms learned how to distinguish between different plants and different types of sounds, and were ultimately able to identify the plant and determine the type and level of stress from the recordings. Moreover, the algorithms identified and classified plant sounds even when the plants were placed in a greenhouse with a great deal of background noise.

In the greenhouse, the researchers monitored plants subjected to a process of dehydration over time and found that the quantity of sounds they emitted increased up to a certain peak, and then diminished.

“In this study we resolved a very old scientific controversy: we proved that plants do emit sounds!” says Prof. Hadany. “Our findings suggest that the world around us is full of plant sounds, and that these sounds contain information – for example about water scarcity or injury. We assume that in nature the sounds emitted by plants are detected by creatures nearby, such as bats, rodents, various insects, and possibly also other plants – that can hear the high frequencies and derive relevant information. We believe that humans can also utilize this information, given the right tools – such as sensors that tell growers when plants need watering. Apparently, an idyllic field of flowers can be a rather noisy place. It’s just that we can’t hear the sounds.”

In future studies the researchers will continue to explore a range of intriguing questions, such as: What is the mechanism behind plant sounds? How do moths detect and react to sounds emitted by plants? Do other plants also hear these sounds? Stay tuned.

The research team. Credits: Tel Aviv University, CC BY

 

Press release from Tel Aviv University.

Case report of first woman of color possibly cured of HIV published in Cell
A new method to cure HIV—by transplanting HIV-resistant stem cells from umbilical cord blood—has yielded long-term successful results, say scientists. The approach was successfully used to treat the “New York patient,” a middle-aged woman with leukemia and HIV who self-identifies as mixed race, who has been without HIV since 2017. Using stem cells from cord blood rather than from compatible adult donors, as has been done previously, increases the potential to cure HIV via stem cell transplantation in people of all racial backgrounds.

Case report of first woman of color possibly cured of HIV. Picture by StockSnap

The researchers share the full results March 16 in the journal Cell; preliminary details on the case study were presented in February 2022 at the 29th annual Conference on Retroviruses and Opportunistic Infections.

“The HIV epidemic is racially diverse, and it’s exceedingly rare for persons of color or diverse race to find a sufficiently matched, unrelated adult donor,” says Yvonne Bryson of UCLA, who co-led the study with fellow pediatrician and infectious disease expert Deborah Persaud (@persaud_deborah) of the Johns Hopkins University School of Medicine. “Using cord blood cells broadens the opportunities for people of diverse ancestry who are living with HIV and require a transplant for other diseases to attain cures.”

Nearly 38 million people around the world live with HIV, and antiviral treatments, while effective, must be taken for life. The “Berlin patient” was the first person to be cured of HIV in 2009, and since then, two other men—the “London patient” and “Düsseldorf patient”—have also been rid of the virus. All three received stem cell transplants as part of their cancer treatments, and in all cases, the donor cells came from compatible or “matched” adults carrying two copies of the CCR5-delta32 mutation, a natural mutation that confers resistance to HIV by preventing the virus from entering and infecting cells.

Only around 1% of white people are homozygous for the CCR5-delta32 mutation and it is even rarer in other populations. This rarity limits the potential to transplant stem cells carrying the beneficial mutation into patients of color because stem cell transplants usually require a strong match between donor and recipient.

Knowing it would be almost impossible to find the New York patient a compatible adult donor with the mutation, the team instead transplanted CCR5-delta32/32-carrying stem cells from banked umbilical cord blood to try to cure both her cancer and HIV simultaneously. The patient received her transplant in 2017 at Weill Cornell Medicine thanks to a team of transplant specialists led by Drs. Jingmei Hsu and Koen van Besien. Her case was part of the NIH-sponsored International Maternal Adolescent AIDS Clinical Trials (IMPAACT) Network and was co-endorsed by the Adult AIDS Clinical Trials Network (ACTG).

The umbilical cord blood cells were infused alongside stem cells from one of the patient’s relatives to increase the procedure’s chance of success.

“With cord blood, you may not have as many cells, and it takes a little longer for them to populate the body after they’re infused,” says Bryson. “Using a mixture of stem cells from a matched relative of the patient and cells from cord blood gives the cord blood cells a kick start.”

The transplant successfully put both the patient’s HIV and leukemia into remission, and this remission has now lasted more than four years. Thirty-seven months after the transplant, the patient was able to cease taking HIV antiviral medication. The doctors, who continue to monitor her, say she has now been HIV negative for more than 30 months since stopping antiviral treatment (at the time that the study was written, it had only been 18 months).

“Stem cell transplants with CCR5-delta32/32 cells offer a two-for-one cure for people living with HIV and blood cancers,”

says Persaud. However, because of the invasiveness of the procedure, stem cell transplants (both with and without the mutation) are only considered for people who need a transplant for other reasons, and not for curing HIV in isolation; before a patient can undergo a stem cell transplant, they need to undergo chemotherapy or radiation therapy to destroy their existing immune system.

“This study is pointing to the really important role of having CCR5-delta32/32 cells as part of stem cell transplants for HIV patients, because all of the successful cures so far have been with this mutated cell population, and studies that transplanted new stem cells without this mutation have failed to cure HIV,” says Persaud. “If you’re going to perform a transplant as a cancer treatment for someone with HIV, your priority should be to look for cells that are CCR5-delta32/32 because then you can potentially achieve remission for both their cancer and HIV.”

The authors emphasize that more effort needs to go into screening stem cell donors and donations for the CCR5-delta32 mutation.

“With our protocol, we identified 300 cord blood units with this mutation so that if someone with HIV needed a transplant tomorrow, they would be available,” says Bryson, “but something needs to be done [on] an ongoing basis to search for these mutations, and support will be needed from communities and governments.”

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This research was supported by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, the AIDS Clinical Trials Group, the Weill Cornell Medicine-New Jersey Medical School Clinical Trials Unit, the PAVE Collaboratory, the Johns Hopkins CFAR, the IMPAACT Center subspecialty laboratory, the Miami CFAR at the University of Miami Miller School of Medicine, and the ACTG and IMPAACT Networks.

Cell, Hsu et al. “Possible HIV-1 Cure in a Woman Receiving CCR5 Δ32/Δ32 Haplo-Cord Stem Cell Transplant for Acute Myeloid Leukemia” https://www.cell.com/cell/fulltext/S0092-8674(23)00173-3
DOI: http://dx.doi.org/10.1016/j.cell.2023.02.030

Press release from Cell Press.

Watch brain cells in a dish learn to play Pong in real time

Human and mouse neurons in a dish learned to play the video game Pong, researchers report October 12 in the journal Neuron. The experiments are evidence that even brain cells in a dish can exhibit inherent intelligence, modifying their behavior over time.

“From worms to flies to humans, neurons are the starting block for generalized intelligence,” says first author Brett Kagan (@ANeuroExplorer), chief scientific officer at Cortical Labs in Melbourne, Australia. “So, the question was, can we interact with neurons in a way to harness that inherent intelligence?”

To start, the researchers connected the neurons to a computer in such a way where the neurons received feedback on whether their in-game paddle was hitting the ball. They monitored the neuron’s activity and responses to this feedback using electric probes that recorded “spikes” on a grid.

The spikes got stronger the more a neuron moved its paddle and hit the ball. When neurons missed, their playstyle was critiqued by a software program created by Cortical Labs. This demonstrated that the neurons could adapt activity to a changing environment, in a goal-oriented way, in real time.

Pong brain cells play
Watch the video to see the brain cells in a dish learning to play Pong in real time. Picture by Eric Perlin

“We chose Pong due to its simplicity and familiarity, but, also, it was one of the first games used in machine learning, so we wanted to recognize that,” says Kagan, who worked with collaborators from 10 other institutions on the project.

“An unpredictable stimulus was applied to the cells, and the system as a whole would reorganize its activity to better play the game and to minimize having a random response,” he says. “You can also think that just playing the game, hitting the ball and getting predictable stimulation, is inherently creating more predictable environments.”

The theory behind this learning is rooted in the free-energy principle. Simply put, the brain adapts to its environment by changing either its world view or its actions to better fit the world around it.

Pong wasn’t the only game the research team tested. “You know when the Google Chrome browser crashes and you get that dinosaur that you can make jump over obstacles (Project Bolan). We’ve done that and we’ve seen some nice preliminary results, but we still have more work to do building new environments for custom purposes,” says Kagan.

Future directions of this work have potential in disease modeling, drug discoveries, and expanding the current understanding of how the brain works and how intelligence arises.

“This is the start of a new frontier in understanding intelligence,” Kagan says. “It touches on the fundamental aspects of not only what it means to be human but what it means to be alive and intelligent at all, to process information and be sentient in an ever changing, dynamic world.”

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Financial support was provided by Cortical Labs.

Neuron, Kagan et al. “In vitro neurons learn and exhibit sentience when embodied in a simulated gameworld.” Link: https://www.cell.com/neuron/fulltext/S0896-6273(22)00806-6

 

Press release from Cell Press.