Friday, September 21, 2018

'Gut Sense' Is Hardwired, Not Hormonal, It’s a Neural superhighway

If you've ever felt nauseous before an important presentation, or foggy after a big meal, then you know the power of the gut-brain connection.

Scientists now believe that a surprising array of conditions, from appetite disorders and obesity to arthritis and depression, may get their start in the gut. But it hasn't been clear how messages in this so-called "second brain" spread from our stomachs to our cerebrum. For decades, researchers believed that hormones in the bloodstream were the indirect channel between the gut and the brain.

Recent research suggests the lines of communication behind that "gut feeling" is more direct and speedy than a diffusion of hormones. Using a rabies virus jacked up with green fluorescence, Duke researchers traced a signal as it traveled from the intestines to the brainstem of mice. They were shocked to see the signal cross a single synapse in under 100 milliseconds -- that's faster than the blink of an eye.

Credit: Duke University

"Scientists talk about appetite in terms of minutes to hours. Here we are talking about seconds," said Diego Bohórquez, Ph.D., senior author of the study and assistant professor of medicine at Duke University School of Medicine. "That has profound implications for our understanding of appetite. Many of the appetite suppressants that have been developed target slow-acting hormones, not fast-acting synapses. And that's probably why most of them have failed."

The research appears Sept. 21 in the journal Science.

Your brain takes in information from all five senses -- touch, sight, hearing, smell and taste -- through electrical signals, which travel along long nerve fibers that lie beneath your skin and muscle like fiber optic cables. These signals move fast, which is why the scent of freshly baked cookies seems to hit you the moment you open a door.

Though the gut is just as important a sensory organ as your eyes and ears -- after all, knowing when your stomach is in need of a fill-up is key to survival -- scientists thought it delivered its messages by a multi-step, somewhat indirect process. Nutrients in your gut, the thinking went, stimulated the release of hormones, which entered the bloodstream minutes to hours after eating, eventually exerting their effects on the brain.

They were partly right. That tryptophan in your turkey dinner is notorious for its transformation into serotonin, the brain chemical that makes you feel sleepy.

But Bohórquez suspected the brain had a way of perceiving cues from the gut more quickly. He noticed that the sensory cells lining the gut shared many of the same characteristics as their cousins on the tongue and in the nose. In 2015, he published a landmark study in the Journal of Clinical Investigation showing that these gut cells contained nerve endings or synapses, suggesting that they might tap into some kind of neural circuitry.

In this study, Bohórquez and his team set out to map that circuitry. First, postdoctoral fellow Maya Kaelberer pumped a rabies virus carrying a green fluorescent tag into the stomachs of mice. She saw that the virus had labeled the vagus nerve before landing in the brainstem, showing her there was a direct circuit.

Next, Kaelberer recreated the gut-brain neural circuit by growing sensory gut cells of mice in the same dish with vagal neurons. She saw the neurons crawl along the surface of the dish to connect to the gut cells and begin to fire signals. When the research team added sugar to the mix, the firing rate sped up. Kaelberer measured how fast the information from sugar in the gut was communicated and was shocked to find it was on the order of milliseconds.

That finding suggested that a neurotransmitter like glutamate -- which is involved in conveying other senses like smell and taste -- might act as the messenger. Sure enough, when the researchers blocked the release of glutamate in the sensory gut cells, the messages were silenced.

Bohórquez has data that suggests the structure and function of this circuit will be the same in humans.

"We think these findings are going to be the biological basis of a new sense," Bohórquez said. "One that serves as the entry point for how the brain knows when the stomach is full of food and calories. It brings legitimacy to idea of the 'gut feeling' as a sixth sense."

In the future, Bohórquez and his team are interested in figuring out how this new sense can discern the type of nutrients and caloric value of the foods we eat.

This research was supported by the National Institutes of Health (K01DK-103832, R03DK114500-01, P30DK034987, 1OT2023849-01), an AGA-Elsevier Pilot Research Award, a UNC Center for Gastrointestinal Biology and Disease Research Award, the Defense Advanced Research Projects Agency (ElectRxN2002850300), the Hartwell Foundation, the Dana Foundation, the Grass Foundation and the Howard Hughes Medical Institute.

Contacts and sources:
Karl Bates
Duke University

Citation: "A Gut-Brain Neural Circuit for Nutrient Sensory Transduction," Melanie Maya Kaelberer, Kelly L. Buchanan, Marguerita E. Klein, Bradley E. Barth, Marcia M. Montoya, Xiling Shen, and Diego V. Bohórquez. Science, Sept. 21, 2018. DOI: 10.1126/science.aat5236

A Fast Mass Extinction in South China during the "Great Dying"

It took less than 30,000 years and maybe only thousands, to kill more than 90% of sea creatures and most land species, according to the most precise study ever published about the mass extinction marking the end of the Permian Period.

Earth's greatest mass extinction, also known as the "Great Dying," occurred about 252 million years ago. By some estimates, over 90% of sea creatures and most land-dwelling reptiles disappeared. Even usually resilient plants and insects suffered near annihilation. But how long did it take to wipe out the vast majority of life on Earth? What could have caused such a massive die-off?

Credit: MIT

A recent study published in the Geological Society of America Bulletin on September 19 suggests an answer.

Scientists from China, the USA and Canada combined new high-resolution radiometric dating of seven closely spaced layers of volcanic material from South China's Penglaitan section with detailed biostratigraphy and geochemical analyses. Results show the duration of the end-Permian mass extinction to be about 31 thousand years, essentially instantaneous by geological standards.

"The mass extinction may have occurred in only thousands of years, but the analytical uncertainty of current CA-ID-TIMS dating technique prevents us from getting a more meaningful constraint for less than 30,000 years," said Prof. SHEN Shuzhong from the Nanjing Institute of Geology and Palaeontology (NIGPAS) of the Chinese Academy of Sciences, the lead author of this paper.

The study also suggests that the sudden extinction may have been caused by Siberian flood-basalt eruptions, along with local intensive explosive volcanism that may have started some 420 thousand years before the mass extinction. These events may have significantly reduced the stability of Late Permian ecosystems to the point where a single extreme incident finally resulted in a sudden ecosystem collapse.

Outcrop photos of the Permian-Triassic boundary interval at Penglaitan.
Credit: NIGPAS

For decades, scientists have studied the Permian-Triassic boundary at Meishan in Zhejiang Province, South China, which serves as the international reference for the boundary. But this "condensed section" - a lot of time represented by a small thickness of sediments - makes it difficult to discern if the extinctions were abrupt or gradual.

To deal with this problem, SHEN and colleagues from CAS, MIT, the National Museum of Natural History (Washington, D.C.) and the University of Calgary focused their attention on the Penglaitan section in South China's Guangxi Autonomous Region.

The Penglaitan sediments were deposited in shallow, tropical waters where sediments accumulated more than 100 times faster than in the Meishan beds, making the Penglaitan sediment much thicker than Meishan for a comparable period of time. In other words, only a few centimeters of rock at Meishan are equivalent to meters of sediment in Penglaitan. The expanded section at Penglaitan allowed the scientists to study the events at the Permian-Triassic boundary at a much higher temporal resolution.

In addition to the higher sedimentation rates, the Penglaitan section has better geochronologic and stratigraphic controls, and rich palaeontological data, enabling examination of the fine structure of the extinction and coeval environmental perturbations.

SHEN and his colleagues documented a rich Late Permian biota at Penglaitan, with at least 10 major marine fossil groups, including brachiopods, ammonoids, sponges, corals, conodonts, foraminifera, bryozoans, bivalves, and trilobites. Twenty-nine of the 66 Permian species identified in the section disappeared within or at the top of a single bed of volcanic ash-rich sandstone (Bed 141). Moreover, there is no "survival interval" of Permian taxa extending into the Early Triassic. This highly diverse marine ecosystem suddenly disappeared during the time of deposition of Bed 141.

The radiometric ages of the Siberian Traps volcanism match the radiometric dates recovered from the volcanic ash beds preserved at Penglaitan and Meishan. The overlap in dates suggests that the environmental effects of volcanic gases like carbon dioxide, methane and sulfur dioxide could have been deadly. A lethal greenhouse warming, oceans depleted of dissolved oxygen, acid rain, and atmospheric pollution by heavy metals would have made life difficult.

Previously, scientists working on the problem were not even sure whether there was one pulse or two pulses of extinction at the Permian-Triassic boundary, or whether some Permian species actually survived into the earliest Triassic beds. These problems could not be resolved in condensed sections like Meishan. In contrast, the Permian deposits at Penglaitan contain more than 50 volcanic ash layers and volcanic ash-rich sandstone beds, possibly produced by pyroclastic flows from the nearby volcanic arc eruption centers in South China, thus presenting a clearer picture of the extinction period. The abrupt change in deposition from the uppermost Permian limestones and ash-rich sandstones to black shale with centimeter-scale limestone interbeds in the lowermost Triassic clearly represents a major shift in the oceanic environment.

The Permian extinction has in the past been linked to a time of rapid climate warming, potentially produced by carbon dioxide and methane emissions from the massive Siberian flood basalt eruptions.

High-resolution paleotemperature measurements across the mass extinction interval suggest a substantial warming of up to 10 degrees Celsius immediately after the mass extinction event. "This might explain the shift in sediment type from limestones in the Permian to early Triassic black shales, indicating ocean anoxia," said SHEN.

A warming climate may cause ocean currents to become sluggish while at the same time bringing increased nutrients into the sea from increased weathering and river runoff. The reduction in mixing of oxygen-rich waters from the ocean surface with deeper waters, and the increase in ocean productivity triggered by the increased nutrient supply, could have led to increased organic carbon deposition and resulting ocean anoxia.

Contacts and sources:
Chen Xiaozheng
Chinese Academy of Sciences Headquarters

Citation: A sudden end-Permian mass extinction in South China
Shu-Zhong Shen Jahandar Ramezani Jun Chen Chang-Qun Cao Douglas H. Erwin Hua Zhang Lei XiangShane D. Schoepfer Charles M. Henderson Quan-Feng Zheng Samuel A. Bowring Yue Wang Xian-Hua LiXiang-Dong Wang Dong-Xun Yuan Yi-Chun Zhang Lin Mu Jun Wang Ya-Sheng Wu
GSA Bulletin (2018)