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The human gut microbiome is diverse and dominated by trillions of bacteria with as many as one-thousand different bacterial species. These microbes thrive in the harsh conditions of the gut and are heavily involved in maintaining healthy nutrition, normal metabolism, and proper immune function. They aid in the digestion of non-digestible carbohydrates, the metabolism of bile acid and drugs, and in the synthesis of amino acids and many vitamins. A number of gut microbes also produce antimicrobial substances that protect against pathogenic bacteria.

Microbiota of the oral cavity number in the millions and include archaea, bacteria, fungi, protists, and viruses. These organisms exist together and most in a mutualistic relationship with the host, where both the microbes and the host benefit from the relationship. While the majority of oral microbes are beneficial, preventing harmful microbes from colonizing the mouth, some have been known to become pathogenic in response to environmental changes. Bacteria are the most numerous of the oral microbes and include Streptococcus, Actinomyces, Lactobacterium, Staphylococcus, and Propionibacterium.

You’re in a collective extended “survival vehicle” relationship.

In a kind of no-brainer biochemical “social contract,” bacterial colonies, like human communities, have to handle the “common good” (suppressing cheating, free-riding, the “tragedy of the commons,” etc).

We dominate because we’re the best cooperators (Yuval Harari).

Evolution is itself a free-floating logic pattern (for discovering other, ever more effective logic patterns, and enacting “competence without comprehension").

Evolution’s logic is like geometry’s: in both relevant patterns and results arise from the intrinsic logic of the elements involved. In geometry, it’s lines, planes, etc. In evolution it’s kinetic functions like survival, varying replication, and adaptation.

STEIN: The brain connections of people whose microbes are dominated by one species of bacteria look different than those of people whose microbes are dominated by another species. That suggests that the specific mix of microbes in our guts helps determine what kinds of brains we have, how our brain circuits develop, how they're wired.

STEIN: It worked the other way around too. The bold mice became timid when they got the microbes of anxious ones. Aggressive mice also calmed down when the scientists altered their microbes by changing their diet, feeding them probiotics, or dosing them with antibiotics.

They did things like replace the gut bacteria of anxious mice with bacteria from fearless mice.

COLLINS: And this resulted in a change in behavior. The mice became a little bit less anxious, a little bit more gregarious.

This could help explain why some people are born with brains that don't work the way they're supposed to, causing problems like autism, anxiety, depression.

STEIN: Finally, these scientists figured out how the microbes in the guts of the mice were communicating with their brains - by sending signals up a big nerve known as the vagus nerve.

All this is raising the possibility that scientists could create drugs that mimic these signals. Or just give people the good bacteria - probiotics - to prevent or treat problems involving the brain.

The researchers, at the Northeastern University in Boston, Massachusetts, turned to the source of nearly all antibiotics - soil.

It allowed the unique chemistry of soil to permeate the room, but kept the bacteria in place for study.

The scientists involved believe they can grow nearly half of all soil bacteria.

uncultured bacteria do harbour novel chemistry that we have not seen before. That is a promising source of new antimicrobials and will hopefully help revive the field of antibiotic discovery."

The researchers also believe that bacteria are unlikely to develop resistance to teixobactin.

There are limits to the discovery of the antibiotic teixobactin, which has yet to be tested in people.

Globally, the numbers can be even worse, and the stakes often higher. “Say a person comes into the hospital in Sierra Leone with a fever and flulike symptoms,” DeRisi says. “After a few days, or a week, they die. What caused that illness? Most of the time, we never find out. Because if the cause isn’t something that we can culture and test for” — like hepatitis, or strep throat — “it basically just stays a mystery.”

It would be better, DeRisi says, to watch for rare cases of mystery illnesses in people, which often exist well before a pathogen gains traction and is able to spread.

Based on a retrospective analysis of blood samples, scientists now know that H.I.V. emerged nearly a dozen times over a century, starting in the 1920s, before it went global.

Zika was a relatively harmless illness before a single mutation, in 2013, gave the virus the ability to enter and damage brain cells.

The beauty of this approach” — running blood samples from people hospitalized all over the world through his system, known as IDseq — “is that it works even for things that we’ve never seen before, or things that we might think we’ve seen but which are actually something new.”

In this scenario, an undiscovered or completely new virus won’t trigger a match but will instead be flagged. (Even in those cases, the mystery pathogen will usually belong to a known virus family: coronaviruses, for instance, or filoviruses that cause hemorrhagic fevers like Ebola and Marburg.)

And because different types of bacteria require specific conditions in order to grow, you also need some idea of what you’re looking for in order to find it.

The same is true of genomic sequencing, which relies on “primers” designed to match different combinations of nucleotides (the building blocks of DNA and RNA).

Even looking at a slide under a microscope requires staining, which makes organisms easier to see — but the stains used to identify bacteria and parasites, for instance, aren’t the same.

The practice that DeRisi helped pioneer to skirt this problem is known as metagenomic sequencing

Unlike ordinary genomic sequencing, which tries to spell out the purified DNA of a single, known organism, metagenomic sequencing can be applied to a messy sample of just about anything — blood, mud, seawater, snot — which will often contain dozens or hundreds of different organisms, all unknown, and each with its own DNA. In order to read all the fragmented genetic material, metagenomic sequencing uses sophisticated software to stitch the pieces together by matching overlapping segments.

The assembled genomes are then compared against a vast database of all known genomic sequences — maintained by the government-run National Center for Biotechnology Information — making it possible for researchers to identify everything in the mix

Traditionally, the way that scientists have identified organisms in a sample is to culture them: Isolate a particular bacterium (or virus or parasite or fungus); grow it in a petri dish; and then examine the result under a microscope, or use genomic sequencing, to understand just what it is. But because less than 2 percent of bacteria — and even fewer viruses — can be grown in a lab, the process often reveals only a tiny fraction of what’s actually there. It’s a bit like planting 100 different kinds of seeds that you found in an old jar. One or two of those will germinate and produce a plant, but there’s no way to know what the rest might have grown into.

Such studies have revealed just how vast the microbial world is, and how little we know about it

“The selling point for researchers is: ‘Look, this technology lets you investigate what’s happening in your clinic, whether it’s kids with meningitis or something else,’” DeRisi said. “We’re not telling you what to do with it. But it’s also true that if we have enough people using this, spread out all around the world, then it does become a global network for detecting emerging pandemics

One study found more than 1,000 different kinds of viruses in a tiny amount of human stool; another found a million in a couple of pounds of marine sediment. And most were organisms that nobody had seen before.

After the Biohub opened in 2016, one of DeRisi’s goals was to turn metagenomics from a rarefied technology used by a handful of elite universities into something that researchers around the world could benefit from

metagenomics requires enormous amounts of computing power, putting it out of reach of all but the most well-funded research labs. The tool DeRisi created, IDseq, made it possible for researchers anywhere in the world to process samples through the use of a small, off-the-shelf sequencer, much like the one DeRisi had shown me in his lab, and then upload the results to the cloud for analysis.

he’s the first to make the process so accessible, even in countries where lab supplies and training are scarce. DeRisi and his team tested the chemicals used to prepare DNA for sequencing and determined that using as little as half the recommended amount often worked fine. They also 3-D print some of the labs’ tools and replacement parts, and offer ongoing training and tech support

The metagenomic analysis itself — normally the most expensive part of the process — is provided free.

But DeRisi’s main innovation has been in streamlining and simplifying the extraordinarily complex computational side of metagenomics

IDseq is also fast, capable of doing analyses in hours that would take other systems weeks.

“What IDseq really did was to marry wet-lab work — accumulating samples, processing them, running them through a sequencer — with the bioinformatic analysis,”

“Without that, what happens in a lot of places is that the researcher will be like, ‘OK, I collected the samples!’ But because they can’t analyze them, the samples end up in the freezer. The information just gets stuck there.”

Meningitis itself isn’t a disease, just a description meaning that the tissues around the brain and spinal cord have become inflamed. In the United States, bacterial infections can cause meningitis, as can enteroviruses, mumps and herpes simplex. But a high proportion of cases have, as doctors say, no known etiology: No one knows why the patient’s brain and spinal tissues are swelling.

When Saha and her team ran the mystery meningitis samples through IDseq, though, the result was surprising. Rather than revealing a bacterial cause, as expected, a third of the samples showed signs of the chikungunya virus — specifically, a neuroinvasive strain that was thought to be extremely rare. “At first we thought, It cannot be true!” Saha recalls. “But the moment Joe and I realized it was chikungunya, I went back and looked at the other 200 samples that we had collected around the same time. And we found the virus in some of those samples as well.”

Until recently, chikungunya was a comparatively rare disease, present mostly in parts of Central and East Africa. “Then it just exploded through the Caribbean and Africa and across Southeast Asia into India and Bangladesh,” DeRisi told me. In 2011, there were zero cases of chikungunya reported in Latin America. By 2014, there were a million.

Chikungunya is a mosquito-borne virus, but when DeRisi and Saha looked at the results from IDseq, they also saw something else: a primate tetraparvovirus. Primate tetraparvoviruses are almost unknown in humans, and have been found only in certain regions. Even now, DeRisi is careful to note, it’s not clear what effect the virus has on people. “Maybe it’s dangerous, maybe it isn’t,” DeRisi says. “But I’ll tell you what: It’s now on my radar.

it reveals a landscape of potentially dangerous viruses that we would otherwise never find out about. “What we’ve been missing is that there’s an entire universe of pathogens out there that are causing disease in humans,” Imam notes, “ones that we often don’t even know exist.”

“The plan was, Let’s let researchers around the world propose studies, and we’ll choose 10 of them to start,” DeRisi recalls. “We thought we’d get, like, a couple dozen proposals, and instead we got 350.”

Metagenomic sequencing is especially good at what scientists call “environmental sampling”: identifying, say, every type of bacteria present in the gut microbiome, or in a teaspoon of seawater.

“When you draw blood from someone who has a fever in Ghana, you really don’t know very much about what would normally be in their blood without fever — let alone about other kinds of contaminants in the environment. So how do you interpret the relevance of all the things you’re seeing?”

Such criticisms have led some to say that metagenomics simply isn’t suited to the infrastructure of developing countries. Along with the problem of contamination, many labs struggle to get the chemical reagents needed for sequencing, either because of the cost or because of shipping and customs holdups

we’re less likely to be caught off-guard. “With Ebola, there’s always an issue: Where’s the virus hiding before it breaks out?” DeRisi explains. “But also, once we start sampling people who are hospitalized more widely — meaning not just people in Northern California or Boston, but in Uganda, and Sierra Leone, and Indonesia — the chance of disastrous surprises will go down. We’ll start seeing what’s hidden.”

offers new insights into the contributions made by the fungus to plant degradation

identification of enzymes capable of degrading lignocelluloses could also be a boon for the biofuels industry. Biofuel companies already use enzyme blends to break down starches from plant biomass, most commonly corn, into sugars to be fermented into ethanol. But the enzymes currently available can’t break down tough-to-degrade molecules such as lignocelluloses on an industrial scale.

idea is that the genes coding for these enzymes in the fungus gardens of leafcutter ants can be mass-produced in the lab by inserting them into E. coli or yeast, then used to break down feedstocks that require less land, fewer resources, and that don’t compete with food crops. “This is a highly evolved system, so the hypothesis is that the enzymes would be highly tuned to break down plant biomass,”

researchers will also need to take into account the role of bacteria. “It could be that bacteria are producing some enzymes that enhance the efficacy of the fungal enzymes,” says Aylward. “Integrating the bacterial component is likely to be important, because the synergism we see with leafcutter gardens is on the level of the entire symbiosis.”

In the late 1900s, researchers discovered that mitochondria were free-living bacteria at some point in the past. Somehow they were drawn inside another cell, providing new fuel for their host. In 2015, Thijs Ettema of Uppsala University in Sweden and his colleagues discovered fragments of DNA in sediments retrieved from the Arctic Ocean. The fragments contained genes from a species of archaea that seemed to be closely related to eukaryotes.Dr. Ettema and his colleagues named them Asgard archaea. (Asgard is the home of the Norse gods.) DNA from these mystery microbes turned up in a river in North Carolina, hot springs in New Zealand and other places around the world.

Masaru K. Nobu, a microbiologist at the National Institute of Advanced Industrial Science and Technology in Tsukuba, Japan, and his colleagues managed to grow these organisms in a lab. The effort took more than a decade.The microbes, which are adapted to life in the cold seafloor, have a slow-motion existence. Prometheoarchaeum can take as long as 25 days to divide. By contrast, E. coli divides once every 20 minutes.

In the lab, the researchers mimicked the conditions in the seafloor by putting the sediment in a chamber without any oxygen. They pumped in methane and extracted deadly waste gases that might kill the resident microbes.The mud contained many kinds of microbes. But by 2015, the researchers had isolated an intriguing new species of archaea. And when Dr. Ettema and colleagues announced the discovery of Asgard archaea DNA, the Japanese researchers were shocked. Their new, living microbe belonged to that group.The researchers then undertook more painstaking research to understand the new species and link it to the evolution of eukaryotes.The researchers named the microbe Prometheoarchaeum syntrophicum, in honor of Prometheus, the Greek god who gave humans fire — after fashioning them from clay.

This finding suggests that the proteins that eukaryotes used to build complex cells started out doing other things, and only later were assigned new jobs.Dr. Nobu and his colleagues are now trying to figure out what those original jobs were. It’s possible, he said, that Prometheoarchaeum creates its tentacles with genes later used by eukaryotes to build cellular skeletons.

Before the discovery of Prometheoarchaeum, some researchers suspected that the ancestors of eukaryotes lived as predators, swallowing up smaller microbes. They might have engulfed the first mitochondria this way.

Instead of hunting prey, Prometheoarchaeum seems to make its living by slurping up fragments of proteins floating by. Its partners feed on its waste. They, in turn, provide Prometheoarchaeum with vitamins and other essential compounds.

We have that genetic element that would allow for bacteria that are resistant to every antibiotic.”

colistin

We are one step away from CRE strains that cannot be treated with antibiotics.

overuse of antibiotics in people and in animals put human health at risk by reducing the power of the drugs,

There's nothing metaphorical about "gut feelings," for what happens in the gut really does influence what we feel. Nor is it just the gastrointestinal tract that alters our minds. Mr. Damasio has shown that neurological patients who are unable to detect changes in their own bodies, like an increased heart rate or sweaty palms, are also unable to make effective decisions

This research shows that the immateriality of mind is a deep illusion. Although we feel like a disembodied soul, many feelings and choices are actually shaped by the microbes in our gut and the palpitations of our heart.

living organisms concentrate carbon-12 in their cells—and when they die, that signature persists. When scientists find graphite that’s especially enriched in carbon-12, relative to carbon-13, they can deduce that living things were around when that graphite was first formed. And that’s exactly what the Tokyo team found in the Saglek Block—grains of graphite, enriched in carbon-12, encased within 3.95-billion-year-old rock.

the team calculated the graphite was created at temperatures between 536 and 622 Celsius—a range that’s consistent with the temperatures at which the surrounding metamorphic rocks were transformed. This suggests that the graphite was already there when the rocks were heated and warped, and didn’t sneak in later. It was truly OG—original graphite.

Still, all of this evidence suggests Earth was home to life during its hellish infancy, and that such life abounded in a variety of habitats. Those pioneering organisms—bacteria, probably—haven’t left any fossils behind. But Sano and Komiya hope to find some clues about them by analyzing the Saglek Block rocks. The levels of nitrogen, iron, and sulfur in the rocks could reveal which energy sources those organisms exploited, and which environments they inhabited. They could tell us how life first lived.

As our sexuality becomes ever more divorced from emotion and intimacy, a process already well underway, sex will increasingly be seen as simply a matter of provoking orgasm in the most efficient, reliable ways possible.

Human sexuality will continue to be subjected to the same commodification and mechanization as other aspects of our lives. Just as the 21st century saw friends replaced by Facebook friends, nature replaced by parks, ocean fisheries replaced by commercially farmed seafood, and sunshine largely supplanted by tanning salons, we’ll see sexual interaction reduced to mechanically provoked orgasm as human beings become ever more dominated by the machines and mechanistic thought processes that developed in our brains and societies like bacteria in a petri dish.

Gender identity will fade away as sexual interaction becomes less “human” and we grow less dependent upon binary interactions with other people. As more and more of our interactions take place with non-human partners, others’ expectations and judgments will become less relevant to the development of sexual identity, leading to greater fluidity and far less urgency and passion concerning sexual expression.

the collapse of western civilization may well be the best thing that could happen for human sexuality. Following the collapse of the consumerist, competitive mind-set that now dominates so much of human thought, we’d possibly be free to rebuild a social world more in keeping with our preagricultural origins, characterized by economies built upon sharing rather than hoarding, a politics of respect rather than of power, and a sexuality of intimacy rather than alienation.

In support of that idea, half a dozen Nobel laureates and other prominent scientists are working with two small companies offering NR supplements.

This time his lab made headlines by reporting that the mitochondria in muscles of elderly mice were restored to a youthful state after just a week of injections with NMN (nicotinamide mononucleotide), a molecule that naturally occurs in cells and, like NR, boosts levels of NAD.

It should be noted, however, that muscle strength was not improved in the NMN-treated mice

a single dose of NR resulted in statistically significant increases” in NAD in humans—the first evidence that supplements could really boost NAD levels in people.

When NAD levels drop, as they do with aging, SIRT1 activity falls off, which in turn makes the crucial signals fade, leading to mitochondrial dysfunction and all the ill effects that go with it.

NAD boosters might work synergistically with supplements like resveratrol to help reinvigorate mitochondria and ward off diseases of aging

Test-tube and rodent studies also suggest that pterostilbene is more potent than resveratrol when it comes to improving brain function, warding off various kinds of cancer and preventing heart disease.

Even before Sinclair's paper, researchers had shown in 2012 that when given doses of NR, mice on high-fat diets gained 60 percent less weight than they did on the same diets without NR. Further, none of the mice on NR showed signs of diabetes, and their energy levels improved. The scientists reportedly characterized NR's effects on metabolism as "nothing short of astonishing."

The Sinclair group's NAD paper drew attention partly because it showed a novel way that NAD and sirtuins work together. The researchers discovered that cells' nuclei send signals to mitochondria that are needed to maintain their normal operation. SIRT1 helps insure the signals get through. When NAD levels drop, as they do with aging, SIRT1 activity falls off, which in turn makes the crucial signals fade, leading to mitochondrial dysfunction and all the ill effects that go with it.

Test-tube and rodent studies also suggest that pterostilbene is more potent than resveratrol when it comes to improving brain function, warding off various kinds of cancer and preventing heart disease.

How will you and the CDC help ensure a well-executed program?

Right, and one of the things that will help tuberculosis control is the test and treat approach, and increasing the proportion of HIV-positive people that are treated. The majority of TB cases currently occur before people are started on anti-HIV medicines.

Partly it's the characteristic of the bacteria: You require long-term treatment for many months, we don't have a vaccine as we do with measles or polio, but partly it's the nature of the control program.

Fundamentally, what happens with tuberculosis will depend on two things. First, how well we implement what we know today, and second, how quickly we get better tools to stop tuberculosis.

If we could figure out which of them are going to develop active TB and provide shorter, more effective treatments for them, then we might really be able to knock down tuberculosis cases.