Microbiome heroes and villains

Escherischia Coli (it may be bad or indifferent, but it is pretty)

Time to wrap up this series, for now.  Let’s finish with three bacteria: Faecalibacterium prausnitzii, Escherischia coli, and Clostridium difficile.  The good, the bad, and the ugly.

Everybody has heard of E Coli; beaches are closed to swimming because of high coliform counts.  This gives the impression that it is the main bacteria found in feces, but that’s far from the case.  They make up less than one percent of the mix, but they are easy to culture.  Their presence in a water or food sample indicate fecal contamination, but they are usually harmless.  Usually; but the group includes the nasty O157:H7 variant, a relatively recent arrival that incorporates some genes from the Shigella bacteria.  Feedlots may be where these genes were acquired, giving rise to hamburger disease and the Walkerton crisis.  If Theodor Escherisch came back, he would not recognize his formerly innocuous bacteria.

Clostridium difficile

C-diff, Clostridium difficile, became notorious in the early 2000s.  Virulent strains in hospitals in Quebec and Alberta killed several patients in 2003, and over 100 have died in Canada alone since.  This is an infection contracted via the oral-fecal route (yes, they like our gut) that causes fever, diarrhea, and sepsis.  This ugly critter likes to colonize the guts of people who have been treated with antibiotics; like a weed, they colonize the empty gut faster than other bacteria. (Surprisingly, it owes its name not to the difficulties it causes but to the fact that it is very fastidious and difficult to culture.)

Faecalibacterium praustnitzii (no, it doesn’t wear a cape)

But where there are villains is bound to be a hero. Faecalibacterium prausnitzii is one of these.  Moises Velasquez-Manoff wrote a really interesting article on how this particular bug was identified and its positive role in the gut realized:

In the mid-2000s Harry Sokol, a gastroenterologist at Saint Antoine Hospital in Paris, was surprised by what he found when he ran some laboratory tests on tissue samples from his patients with Crohn’s disease, a chronic inflammatory disorder of the gut. The exact cause of inflammatory bowel disease remains a mystery. Some have argued that it results from a hidden infection; others suspect a proliferation of certain bacteria among the trillions of microbes that inhabit the human gut. But when Sokol did a comparative DNA analysis of diseased sections of intestine surgically removed from the patients, he observed a relative depletion of just one common bacterium, Faecalibacterium prausnitzii. Rather than “bad” microbes prompting disease, he wondered, could a single “good” microbe prevent disease?

F. praustnitzii is one of the more common bacteria in the human gut, and its relative absence has been associated with Crohn’s disease, but also with obesity, asthma, and depression – not bad for a single type of bacteria.  And yes, they like dietary fiber, please.

What is surprising to be is how similar this particular bacterium is to several black sheep in its cluster class, Clostridium IV.  This includes the various clostridia that cause botulism, gas gangrene, and tetanus. There is still so much to learn about our very own bacteria.  Don’t be surprised if you’re asked for fecal samples more often in the future.

 

This is the final post of this microbiome series. The previous post, on gut bacteria and asthma, can be found here.

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Asthma (wheeze!) and gut bacteria

Archaeon Methanobrevibacter smithii (one of the main methane makers in the gut)

Asthma is another respiratory disease that has been convincing linked with the activity of gut bacteria, the so-called gut-lung axis. But there is something special about asthma: the link between bacteria and disease is much clearer than in the other ones discussed in this series.

Whether or not a person will be likely to become asthmatic seems to be determined at a very early age. Tori Rodriguez summarizes recent findings stating that the gut microflora composition during the first two years of life has a clear incidence on the likelihood of developing asthma (or other allergy problems) by age five.  She mentions

age-dependent regulation of immunoglobulin E production by the gut microbiota and a potential direct role for specific bacteria, such as LachnospiraVeillonellaFaecalibacterium, and Rothia, in mitigating asthma development.

Immunoglobulin E are antibodies linked to allergic reactions, which may be produced as a response to short-chain fatty acids produced by some bacteria. If these acids accumulate, they may trigger the gut secretion of antibodies linked to asthma.  Such acids (and other metabolic products) are consumed by desirable bacteria such as the ones listed above; so their presence indirectly prevents the production of antibodies.

Asthmatics and other readers may find the following technical review articles interesting, here and here. In particular, the fact that an asthmatic mother may transfer asthma to her newborn by passing on a deficient microbiome is interesting and points to a possible treatment. (Yes, fecal transplants may solve everything, it seems!)

But it may not even be bacteria that are involved; the microbiome contains multitudes of other groups.  A recent study reported that a high concentration of an archaeon, Methanosphaera stadtmanae, significantly lowers risk of asthma.  This is one of these exotic methane producers that are nearly impossible to culture and that can only be identified by fecal DNA analysis (and rarer than Methanobrevibacter smithii pictured above, which has no influence on asthma, according to the same study). The things you learn from shit…

 

This is the tenth post in this microbiome series. The previous post on Alzheimer’s disease and gut bacteria can be found here.

The microbiome and Alzheimer’s disease

Even though the disease was first described by Alois Alzheimer over a century ago, we still don’t know what causes it.  But recent studies on the link between the gut bacteria and the disease may open new avenues.

Tim Newman, in Medical News Today, reports that

there were measurable differences in the [fecal] samples from people with dementia and from those without it. In particular, the feces of individuals with dementia had higher levels of ammonia, indole, skatole, and phenol.

Bacteroides, which break down these compounds, were unsurprisingly found in lower concentrations in samples from patients with Alzheimer’s; conversely, they had unusually high levels of Ruminococcus.

(As an aside, high concentrations of ammonia and skatole would imply stinkier farts from these patients.  Skatole and indole smell like shit at “normal” concentrations, but at lower levels smell flowery – go figure.)

But how could bacteria in the gut affect the brain?  Emily Woodruff discusses the new findings and similarities with other neurological diseases (and adds a  video to her article, below).  Other researchers confirm the findings (here, here or here), but we’re no closer to understand the steps in the connection.

But at least, it may help explain why people on Mediterranean diet appear to be less prone to developing Alzheimer.  Healthier gut bugs, maybe?

This is the ninth post in this series. The previous post on Parkinson’s disease and the gut can be found here.

The microbiome and Parkinson’s disease

The Michael J Fox foundation hosts a podcast series on Parkinson’s, found at https://podfanatic.com/podcast/the-michael-j-fox-foundation-parkinson-s-podcast

The connection between Parkinson’s disease and the gut is becoming clearer; the disease may actually originate in the gut.  In The Guardian, Nicola Davis writes that

The latest findings, which are based on studies in mice, back up a long-held theory that abnormally folded alpha-synuclein may start off in the gut and then spread to the brain via the vagus nerve – a bundle of fibres that starts in the brainstem and transports signals to and from many of the body’s organs, including the gut.

The study comes months after a different group of researchers revealed that people whose appendix was removed early in life had a reduced risk of later developing Parkinson’s disease – a finding experts said also supports the idea the disease may begin in the gut.

The appendix, of course, hosts a whole variety of bacteria. What is their role? In 2016, researchers at CalTech

discovered for the first time a functional link between bacteria in the intestines and Parkinson’s disease (PD). The researchers show that changes in the composition of gut bacterial populations–or possibly gut bacteria themselves–are actively contributing to and may even cause the deterioration of motor skills that is the hallmark of this disease.

Does that point to a possible cure, via the right microbes?  It’s much too early to say, but there are already suggestions that the right diet may promote the right bacteria. 

A diet for Parkinson’s?

As in most of these links between the microbiome and disease, we can only say “stay tuned”.  But it is fascinating that our shit – our guest bacteria – is really an integral part of us and our health, and that’s reason for hope.

This is the eight post in this series. The previous post, about the impacts of antibiotics pollution, can be found here.

The hot air dryer in the public washroom

Nora Keegan measuring the distance between a dryer and her ears

A good thing, no?  It saves all these paper towels, and there’s no garbage.

But there are a few knocks against them, though.  Most recently a young researcher, Nora Keegan, showed that they are too noisy.

“In Grade 4, I noticed that my ears kind of hurt after the hand dryer,” Keegan told the Calgary Eyeopener. “And then later, at the start of Grade 5, I also noticed that my ears were hurting after I used the hand dryer. So then I decided to test it to see if they were dangerous to hearing, and it turns out they are.” Eventually, Keegan determined that there are two models in particular that are harmful for children’s ears: the Dyson and XCelerator, which both operate at about 110 decibels.

Keegan noticed that children are exposed to higher noise levels since their heads are nearest to where dryers are installed.  She also found that the noise increases when hands are dried (duh – but not something that manufacturers seem to measure).  Her results were published in Paediatrics & Child Health – not bad for a 13-year old!

This is the second knock against air dryers.  The first one is the fact that they stir the air and spread bacteria – “the bacterial horror of hot-air dryers”, trumpets an article from the journal of the Harvard Medical School.

But where do these bacteria come from, anyways?  Well, flushing creates a lot of “bioaerosols”, tiny droplets of water from the toilet bowl (water, and whatever else…); here’s one study that quantifies the problem.  This is due to the fact that public toilets have no lids – why not is beyond me.  That would alleviate the problem by getting at the source (there are aerosolized bacteria in any busy public washrooms because of lack of lids, hot air dryers just make the problem worse).

That points the way to a solution: install lids, and design quieter dryers.  Or just use paper towels.

 

Antibiotics pollution

Indian cattle, from the India Water Portal

Antibiotic resistance is a well known concern, but where is the resistance coming from?  The expectation is that it comes from over-prescription in people and, in particular, in livestock, where it has been used as a preventative, whether or not the animals appear to be sick (thankfully, this will soon change).  The idea is that antibiotics or their metabolites are excreted and then enter the waterways, unaffected by sewage treatment. But New Scientists writers Alice Bomboy and Lise Barnéoud followed the research of Joakim Larsson who traced a source ignored before: pollution by pharmaceutical manufacturers.

Larsson has spent most of his career exploring the impact of pharmaceutical consumption. “Basically, it’s about how the environment is being contaminated through pee and poo,” he says. In 2007, he also turned his attention to pollution from manufacturing, which brought him to Hyderabad. He wanted to see just how much of the antibiotic compounds being produced end up in the local lakes and streams.

What he found was astonishing. In effluent at the local industrial waste-water treatment plant, the concentration of a common antibiotic called ciprofloxacin was 1000 times higher than is required to kill the bacteria it targets – and a million times higher than the levels typically found in sewage outflows elsewhere in the world. “There was enough ciprofloxacin in the effluent leaving the plant each day to treat everyone in a city of 45,000 people,” says Larsson.

The Medak district near Hyderabad, India, specializes in the manufacture of low-cost pharmaceuticals for export.  Bomboy and Lise Barnéoud report that downstream of Medak,

[t]he foetid lakes and streams contain extraordinarily high concentrations of antibiotics, creating reservoirs of the drug-resistant pathogens that kill hundreds of thousands of people every year. Some suspect these places might even be incubating new superbugs that could rapidly spread around the world.

Gaddapotharam Lake, for example, was once used to irrigate rice paddies. It is now so contaminated that farmers have abandoned the area. We also visited Isnapur Lake, right in front of a cluster of pharmaceutical plants, where the smell is so foul that, within minutes, you feel physically sick. Here, Dayakar pointed out tracks left in the muddy banks by the tankers that come at night to dump industrial waste rather than taking it to the local treatment plant.

Cheap antibiotics have been saving lives.  But unfortunately they have been used undiscriminately, which has negative consequences: fostering resistance in pathogens, but also harming the natural gut microbiome.  Obviously, the problem is compounded with this type of illegal pollution, releasing gross amounts into the environment.

You can follow Larsson’s highly interesting (if technical) research from his website at the University of Gothenburg, here. The reference to the article is: Alice Bomboy and Lise Barnéoud: Recipe for Disaster. New Scientist, 5/25/2019, Vol. 242, Issue 3231; paywalled link here.

This is the seventh post in this series.  The previous post, about Autism, can be found here.

Gut bacteria and autism

It seems the microbiome can strongly affect something that would seem unrelated, namely, autism.  An interesting article in The Economist reports on findings from a study conducted by Rosa Krajmalnik-Brown of Arizona State University and her colleagues.  They

tested a process called microbiota transfer therapy (MTT) on 18 autistic children aged between seven and 16. Of their participants 15 were regarded, according to the Childhood Autism Rating Scale, as having “severe” autism. MTT is a prolonged version of a process already used to treat infection by a bug called Clostridium difficile, which causes life-threatening diarrhoea. The researchers gave the children, first, an oral antibiotic, a bowel cleanse and an oral antacid (to ensure that microbes administered by mouth would survive their passage through the stomach). They followed this up with either an oral or a rectal dose of gut bacteria, and then, for seven to eight weeks, a daily antacid-assisted oral dose.

They found, unsurprisingly, that levels of desirable bacteria (bifidobacteria and prevotella) had multiplied. Prevotella was particularly important since it appears to be mostly absent in autistic children. Does that have any effect?

Crucially, these changes in gut bacteria have translated into behavioural changes. Even 18 weeks after treatment started the children had begun showing reduced symptoms of autism. After two years, only three of them still rated as severe, while eight fell below the diagnostic cut-off point for ASD altogether. These eight thus now count as neurotypical.

Exactly how gut bacteria might contribute to autism is a puzzle.

(The article can be found in The Economist, June 1 2019, pg 71-72; the link is paywalled)

This is the sixth post in this series.  The previous post, on what gut bacteria tell about evolution, can be found here.