Cholesterol-chomping gut bacteria can reduce risk of heart attack

The Dark Energy Spectroscopic Instrument experiment has provided the largest and the most precise 3D map of the universe to date.

The rod-shaped Oscillibacter species bacteria take up fluorescently labelled cholesterol (shown here in green). | Photo Credit: Ahmed Mohamed/Broad Institute

CHANGES in the microbiome in the gut have been linked to a range of diseases, including type 2 diabetes, obesity, and inflammatory bowel disease. A recent study has added one more to that list: cardiovascular disease (CVD). The study, published in Cell, was done by a team of researchers at the Broad Institute of MIT and Harvard, along with Massachusetts General Hospital. The team has identified a specific bacterial species that consumes cholesterol in the gut and may help lower its levels and, thus, the risk of CVD.

The researchers analysed metabolites and microbial genomes from more than 1,400 participants in the Framingham Heart Study, a decades-long project focussed on risk factors for CVD. The approach uncovered more than 16,000 associations between microbes and metabolic traits, including one that was particularly strong: People with several species of bacteria from the Oscillibacter genus had lower cholesterol levels than those who lacked the bacteria. The researchers found that these species were surprisingly abundant in the gut, representing on average 1 in every 100 bacteria.

The researchers discovered that Oscillibacter metabolise cholesterol, and they also identified the mechanism the bacteria use to break it down. The results suggest that the gut microbiome can be manipulated in specific, targeted ways to improve cardiovascular health. Even though links between the gut microbiome and CVD risk had been found earlier, the connections were not sufficient to suggest therapies partly because of the lack of a complete understanding of metabolic pathways in the gut. In this study, the team gained a more complete picture of the impact of gut microbes on metabolism. They combined the complete structural and functional profiles of all the microbial DNA in stool samples, with the levels of many known and thousands of unknown metabolites.

To figure out the biochemical pathway the microbes use to break down cholesterol, the team first grew the Oscillibacter bacteria in the laboratory and then used mass spectrometry to identify the most likely by-products of cholesterol metabolism in the bacteria. This allowed them to determine the pathways the bacteria uses to lower cholesterol levels. They found that the bacteria converted cholesterol into intermediate products that can be broken down by other bacteria and excreted from the body. Next, the team used machine-learning models to identify enzymes responsible for this biochemical conversion, and then detected those enzymes and cholesterol breakdown products specifically in certain Oscillibacter in the laboratory.

The DESI instrument is equipped with 5,000 robotic fibres to dramatically speed up data collection.   | Photo Credit: Marilyn Sargent/The Regents of the University of California, Lawrence Berkeley National Laboratory

The DESI twist to dark energy

THE Dark Energy Spectroscopic Instrument (DESI), located at the Kitt Peak National Observatory in Arizona, is an ambitious multilayer astronomy experiment with the aim of improving our understanding of the evolution and fate of the cosmos by gathering light from the most distant parts of the universe. The US Department of Energy’s Lawrence Berkeley National Laboratory manages this multiyear experiment that involves more than 900 researchers from over 70 institutions around the world.

The results of the analyses of the first year of data collected by DESI were presented on April 4 at a meeting of the American Physical Society in California. The results have provided the largest and the most precise 3D map of the universe to date at different slices of aeons up to as far back as 8-11 billion years ago—the universe in its youth so to speak—that helps trace its evolution to what is observed today. While in broad agreement with what is called the standard cosmological model, the results have also thrown up some important questions the answers to which will have great implications for the correct understanding of the universe and its apparent accelerating expansion. The DESI collaboration plans to publish these results in multiple papers through the open access preprint Web platform arXiv.

The first results have confirmed the basics of what scientists hold as the best model of the universe but also hint that the underlying cause (or causes) of cosmic acceleration, the discovery of which led to the Nobel Prize in Physics in 2011, is yet to be properly understood.

Cosmic acceleration is problematic because it is counter-intuitive. Gravity pulls matter together, but at the largest scales, the universe acts as if there is something repulsive pushing it apart and accelerating its expansion. While some scientists believe that “dark energy”, an unknown all-pervasive repulsive force that is not well understood, is responsible for this cosmic acceleration, others theorise that it is a cosmological constant—an intrinsic property of space-time itself—that drives the acceleration.

The Dark Energy Spectroscopic Instrument experiment has made the largest 3D map of the universe to date. The earth is at the centre of this thin slice of the full map. In the magnified section, it is easy to see the underlying structure of matter in the universe. | Photo Credit: Claire Lamman/DESI collaboration; custom colormap package by cmastro.

On the basis of DESI’s 3D maps of the universe DESI, the collaboration has been able to infer the effects of dark energy over the past 11 billion years. This is the first time scientists have measured the expansion history of the young universe with a precision better than 1 per cent.

The leading model of the universe is known as Lambda-CDM. It includes both ordinary matter and a rarely interacting type of matter called cold dark matter (CDM) and dark energy, known as Lambda. Both matter and dark energy shape how the universe expands but in opposing ways. The amount of each influences how the universe evolves. The Lambda-CDM model has been effective at validating results from previous experiments. However, when DESI’s first-year results are combined with data from earlier studies, there are some subtle differences from the Lambda-CDM predictions.

“Our results show some interesting deviations from the standard model of the universe that could indicate that dark energy is evolving over time [emphasis added],” said Mustapha Ishak-Boushaki, one of the scientists presenting the results. That is, dark energy is no longer a cosmological constant; this would call for a modification in Einstein’s theory of gravity. However, this is not settled statistically yet as the deviation is not at the five-sigma level, the statistical gold standard.

With more data we will know whether the deviation persists, which will shed some light on what is causing cosmic acceleration and provide a huge step in our understanding of the evolution of the universe, he added. More data will also improve DESI’s other early results as well, which weigh in on the Hubble constant—a measure of how fast the universe is expanding today—and the mass of particles called neutrinos.