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Gut check

Scientists discover a “mind-blowing” link between gut health and age reversal

“By restoring health in the microbiome we’re able to reverse age-related cognitive deficits,” scientists say about their new study in mice.

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To stave off the effects of aging, one might use retinol creams or play Sudoku.

But maybe we should be focusing on something different altogether.

Scientists have known for the past two decades that the metropolis home to trillions of bacteria in your belly — the gut microbiome — is also central to mental health, the immune system, and more.

One of the latest studies in gut health scrutinizes how our microbiome affects aging in mice, using a surprising transplant.

The research, published Monday in the journal Nature Aging, reveals that older mice who have received gut microbiota transplants from young mice show improved brain function and behavior. This mouse model offers powerful insight into how diet and what populates our stomachs affect what our brains look like in old age.

What’s new — Researchers have found that when they transplant microbiota of young mice into the intestines of older mice, the older mice display improved cognitive function. This is the first study that shows the correlation between transplantation of a gut microbiome from a younger mouse into an older one with improved brain abilities in the older mice.

“It was pretty mind-blowing.”

In an interview with Inverse, Marcus Böhme, a neuroscientist with University College Cork and one of the authors, was effusive in his reaction to the research.

“It was really great to see that full change in their microbiomes can really excel such effects on cognitive behavior, like almost resembling the learning performance of young mice, it was pretty mind-blowing,” says Böhme.

“Maintaining our gut health is really important for the many aspects of normal physiology, particularly as we age,” says Neil Mabbott, an immunopathologist at the University of Edinburgh. (Mabbott was not involved in the study.)

Testing covid-2019 new coronavirus vaccine in laboratory animals
This study examined how cognitive function of older mice improved when they received gut microbiota transplants from younger mice.Shutterstock

How they did it — Do the words “fecal microbiota transplantation” mean anything to you?

Another way to put it is “poo transplant.” That’s how John Cryan, one of the paper’s authors and a neuroscience professor at University College Cork, explains it to Inverse.

They had a group of three or four-month-old mice (akin lifecycle-wise to a healthy 18-year-old human) and a group of 19 or 20-month-old mice (akin to a healthy 70-year-old human).

The researchers collected fecal samples from the younger mice and transplanted them into the older mice’s intestines to cultivate a similar gut microbiome; the bacteria in the fecal samples would flourish in their new environment.

Lo and behold: the older mice who received the transplant from the younger mice had gut microbiota that resembled that of the younger mice.

And then they administered behavioral tests to the older mice to measure how their brain function may have changed. Notably, they conducted an experiment called the Morris water test in which a mouse submerged in a pool of water must navigate its way to a platform.

Finally, Böhme and his colleagues decapitated their mice and poked around their brains, particularly the hippocampus which is the seat of spatial learning and memory, to see how their brains had changed in response to the transplant.

A schematic drawing of a Morris water test
Boehme tested the older mice’s cognitive abilities with a Morris water maze, in which the mice have to navigate a pool and find an invisible platform.Samuel John via Wikimedia Commons

Why it matters — FMT is not going to become the next anti-aging fad, but this experiment does inform us more on how taking care of our gut health can help maintain holistic health into old age.

“There are big implications beyond just brain health,” says Katherine Guzzetta, a Ph.D. student at University College Cork and author on this paper. Guzzetta also astutely notes that knowledge of gut health and healthy elderly minds can also improve our pets’ quality of life, so our cats and dogs can continue to enjoy life into old age.

More immediately, this study could illuminate what aspects of diet are critical for brain health and more in our golden years.

Digging into the details — In particular, the results of the Morris water maze showed the benefits of this transplant. Older mice who had received the transplant from younger mice performed better at the maze than older mice who had not received a transplant.

Cryan says that this behavior is consistent with his team’s findings in the mouse brains. While the transplants gave the older mice the gut microbiomes of younger mice, in turn, parts of their brain appeared younger, too. Specifically, the hippocampus — the region of the brain involved with learning and memory — resembled that of younger mice.

So, it seems that the gut and brain are talking to each other, in a sense. Cryan elaborates that part of this communication comes from the vagus nerve, a “long, wandering nerve” that sends signals from the entire gastrointestinal tract up to the brain. But, that still only accounts for some of the bodily cooperation; there still remains the question of the mechanism behind these changes.

“I'm not recommending thing that we should go into poo transplants.”

What’s next — Hold onto your GI tract: Poo transplants are not coming to humans en masse quite yet.

“I'm not recommending thing that we should go into poo transplants in you and humans, because we have no evidence that that would work in humans,” says Cryan. (Although, FMT is already a successful way to treat the infection C. diff in humans.) “But what we do have evidence then is that targeting the microbes, which is in particularly or with specific microbes that we can identify with strains exactly are missing.”

Mabbott agrees that identifying specific bacteria strains that benefit older gut microbiomes is one of two crucial next steps. “What are other components of their microbiota which are causing this? And what is the mechanism by which they are doing this?” he tells Inverse. “Can we drill down to specific mechanisms here? That might have some very important therapeutic intervention means here.”

“By restoring the microbiome, we’re targeting it through this transplantation, we’re able to reverse age-related cognitive deficits,” says Guzzetta. “That’s mind-blowing.”

Editor’s note: This article has been updated from an earlier version with clarifying quotes from the scientists.

Abstract: The gut microbiota is increasingly recognized as an important regulator of host immunity and brain health. The aging process yields dramatic alterations in the microbiota, which is linked to poorer health and frailty in elderly populations. However, there is limited evidence for a mechanistic role of the gut microbiota in brain health and neuroimmunity during aging processes. Therefore, we conducted fecal microbiota transplantation from either young (3–4 months) or old (19–20 months) donor mice into aged recipient mice (19–20 months). Transplant of a microbiota from young donors reversed aging-associated differences in peripheral and brain immunity, as well as the hippocampal metabolome and transcriptome of aging recipient mice. Finally, the young donor-derived microbiota attenuated selective age-associated impairments in cognitive behavior when transplanted into an aged host. Our results reveal that the microbiome may be a suitable therapeutic target to promote healthy aging.
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A forest fire in June 2021 in Siberia.

Planet in Peril

Satellite images reveal a climate crisis nightmare in Siberia

Understanding this study’s findings “may make the difference between catastrophe and apocalypse.”

Dimitar Dilkoff/Getty Images

Traverse deep into northern Siberia, and you’ll find the Yenisey-Khatanga Basin. As of late, this remote part of the world is predominantly known for two things: its untapped potential as a massive source of oil and gas, and its proximity to the wildfires that have raged in Siberia this summer.

Now, scientists suggest another factor that demands our attention: According to a study published Monday in the journal Proceedings of the National Academy of Sciences, considerable amounts of methane are being released from a previously unexplored source.

Arctic methane is typically connected to two sources: organic matter in permafrost and methyl clathrate (molecules of methane frozen in ice crystals). This study spotlights a third — one released from fractures and pockets in the permafrost zone that’s become unstable due to warming.

As the climate crisis worsens, understanding this study’s findings “may make the difference between catastrophe and apocalypse,” lead author Nikolaus Froitzheim, a professor at the University of Bonn’s Institute of Geosciences in Germany, tells Inverse.

Melting permafrost in Siberia
Permafrost melts into the Kolyma River in Siberia during July 2019. Record-breaking heat waves increase permafrost thaw, triggering the release of methane and contributing to global warming. Getty

What you need to know first — The thawing of the Siberian permafrost — a mixture of rock, ice, soil, and the organic remains of animals and plants — is associated with the release of methane in the atmosphere. Global warming has led to an increased thawing of the permafrost.

Methane is a potent greenhouse gas emission with 84 to 86 times the warming power of carbon dioxide over a 20-year period.

After conducting a satellite analysis of the Yenisey-Khatanga Basin, Froitzheim and colleagues found we’ve been overlooking another crucial source of methane emissions from the Siberian permafrost: sites of “thermogenic methane.”

How the discovery was made— The researchers used an interactive satellite mapping technology, known as PULSE, to calculate methane emissions in the air above the Yenisey-Khatanga Basin in Siberia.

“There is a lot of natural gas in the subsurface of Siberia.”

The researchers looked specifically at methane emissions following a heat wave in Siberia in June 2020, as well as methane emissions in the area in spring 2021. They also compared the methane emissions on the satellite map to a geological map showing where certain rock formations occur.

The researchers then made an alarming discovery:

“We found that two elongated areas of elevated methane concentration on the PULSE map perfectly coincide with two stripes where limestone formations occur in the subsurface,” Froitzheim says.

Satellite map of methane emissions over Siberia
Satellite imagery shows atmospheric methane concentrations during May and August 2020 over the Taymyr Peninsula in Northern Siberia. Nikolaus Froitzheim, Dmitry Zastrozhnov, and GHGSAT.

What’s new — Those limestone formations are likely sites of “thermogenic methane” or natural gas deposits of methane hidden deep underneath the permafrost. Natural gas, the team writes, can be “trapped under or within the permafrost layer and released when it thaws.”

The methane couldn’t have come from the usual microbes breaking down organic matter in the soil, since there is very little soil in these limestone formations.

Heat “made this mixture unstable and opened pathways.”

Instead, Frotzheim suspects record-breaking temperatures disturbed fractures in the limestone, providing an opportunity for natural gas from deeper within the permafrost to escape into the atmosphere.

“Our hypothesis is that the heat made this mixture unstable and opened pathways through which natural gas from depth could reach the surface,” Frotzheim says. “There is a lot of natural gas in the subsurface of Siberia, and some of these reservoirs may have been tapped.”

Comparing maps over a one-year period between May 2020 and May 2021, the scientists found that “atmospheric methane concentrations have increased considerably during and after the 2020 heat wave.”

“After” is key: The increase in methane was highest in June/August 2020 as well as in March/April 2021, demonstrating how warming can trigger methane release long after the initial heat wave.

Why it matters — The events in Northern Siberia are all, in a way, connected: the fires, the hunt for natural fuel, and the release of a powerful greenhouse gas.

Methane traps heat in the atmosphere and plays a major role in climate change. The heat wave that ignited Siberia’s wildfires is part of a trend driven by human-induced climate change — so is the thawing of Siberia’s permafrost. The extraction of oil and gas also releases methane. These factors are all connected.

It’s a domino effect that doesn’t appear to be slowing down: Record-breaking temperatures hit Siberia in 2020 and once again in the summer of 2021.

Siberia
In July 2021, a couple attempts to evade smoke hanging over the city of Yakutsk, in Siberia. Dimitar Dilkoff/Getty Images

As temperatures continue to skyrocket due to the climate crisis, the permafrost thaw may unleash unknown quantities of this deep methane gas into the atmosphere. In 2018, NASA predicted a possible “future boost” of methane from Arctic permafrost — that prediction is coming true.

Based on their findings, the researchers conclude: “As a result, the permafrost–methane feedback may be much more dangerous than suggested by studies accounting for microbial methane alone.”

What’s next — Methane may be coming from deep within the Siberian ice, but scientists are still scratching the surface of permafrost research.

Froitzheim and his colleagues still aren’t sure why methane emissions began spiking more than half a year after the summer 2020 heat wave.

The team calls on more scientists to conduct research to “find out how fast and how much methane may be emitted this way,” including an analysis of methane in air samples and calculations of methane gas destabilization in the rocks.

While these measures are a way for scientists to better understand the exact amount of methane released due to permafrost, they’re not a solution.

These findings don’t necessarily mean the permafrost is beyond repair, the scientists suggest. The amount of methane being released from these deep methane reserves are relatively small compared to, say oilfields in Libya or wetlands in India, Froitzheim says. To have any chance of halting the release of methane from the permafrost we need to immediately begin reducing greenhouse gas emissions from fossil fuels and other industries.

“I do not think that these particular observations mean that we have passed a point of no return,” Frotzheim says.

Abstract: Anthropogenic global warming may be accelerated by a positive feedback from the mobilization of methane from thawing Arctic permafrost. There are large uncertainties about the size of carbon stocks and the magnitude of possible methane emissions. Methane cannot only be produced from the microbial decay of organic matter within the thawing permafrost soils (microbial methane) but can also come from natural gas (thermogenic methane) trapped under or within the permafrost layer and released when it thaws. In the Taymyr Peninsula and surroundings in North Siberia, the area of the worldwide largest positive surface temperature anomaly for 2020, atmospheric methane concentrations have increased considerably during and after the 2020 heat wave. Two elongated areas of increased atmospheric methane concentration that appeared during summer coincide with two stripes of Paleozoic carbonates exposed at the southern and northern borders of the Yenisey-Khatanga Basin, a hydrocarbon-bearing sedimentary basin between the Siberian Craton to the south and the Taymyr Fold Belt to the north. Over the carbonates, soils are thin to nonexistent and wetlands are scarce. The maxima are thus unlikely to be caused by microbial methane from soils or wetlands. We suggest that gas hydrates in fractures and pockets of the carbonate rocks in the permafrost zone became unstable due to warming from the surface. This process may add unknown quantities of methane to the atmosphere in the near future.
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