New 'interspecies communication' strategy between gut bacteria and mammalian hosts uncovered

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New 'interspecies communication' strategy between gut bacteria and mammalian hosts uncovered
Study describes molecular language bacteria use to control host genes and development
Date:February 21, 2019Source:Case Western Reserve UniversitySummary:Bacteria in the gut do far more than help digest food in the stomachs of their hosts; they can also tell the genes in their mammalian hosts what to do. A study describes a form of 'interspecies communication' in which bacteria secrete a specific molecule -- nitric oxide -- that allows them to communicate with and control their hosts' DNA, and suggests that the conversation between the two may broadly influence human health.

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Bacteria in the gut do far more than help digest food in the stomachs of their hosts, they can also tell the genes in their mammalian hosts what to do.

A study published today in Cell describes a form of "interspecies communication" in which bacteria secrete a specific molecule -- nitric oxide -- that allows them to communicate with and control their hosts' DNA, and suggests that the conversation between the two may broadly influence human health.
The researchers out of Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center, and Harvard Medical School tracked nitric oxide secreted by gut bacteria inside tiny worms (C. elegans, a common mammalian laboratory model). Nitric oxide secreted by gut bacteria attached to thousands of host proteins, completely changing a worm's ability to regulate its own gene expression.
The study is the first to show gut bacteria can tap into nitric oxide networks ubiquitous in mammals, including humans. Nitric oxide attaches to human proteins in a carefully regulated manner -- a process known as S-nitrosylation -- and disruptions are broadly implicated in diseases such as Alzheimer's, Parkinson's, asthma, diabetes, heart disease, and cancer.
The findings suggest nitric oxide is a general mechanism by which gut bacteria can communicate with mammalian hosts. Previous work to untangle communication lines to and from gut bacteria has primarily focused on rare molecules that bacteria secrete. The new findings are akin to uncovering a chemical language common across species, as opposed to single words, said senior author Jonathan Stamler, MD, director of the Institute for Transformative Molecular Medicine at Case Western Reserve University School of Medicine and president of the Harrington Discovery Institute at University Hospitals Cleveland Medical Center. "There is tremendous complexity in the gut, and many researchers are after the next unusual substance produced by a bacterium that might affect human health," he says. With trillions of bacteria in the average gut, Stamler decided to look for a common language that all bacterial species might use. "The enormity of the gut bacteria population and its relationship to the host predicts there will be general means to communicate that we humans can recognize."
The researchers demonstrated the phenomenon by feeding developing worms bacteria that produce nitric oxide. They then selected one very important protein -- argonaute protein, or ALG-1 -- that is highly conserved from worms to humans and silences unnecessary genes, including genes critical for development. When nitric oxide secreted by the bacteria attached to ALG-1, they developed malformed reproductive organs and died. Too much nitric oxide from bacteria commanded the worms' DNA silencing proteins and impaired healthy development.
"Practically, animals will not let this happen," Stamler said. Instead, the authors speculate a mammalian host outside of a laboratory setting will adjust to accommodate changing nitric oxide levels. Said Stamler, "The worm is going to be able to stop eating the bacteria that make the nitric oxide, or it will begin to eat different bacteria that makes less nitric oxide, or change its environment, or countless other adaptations. But by the same token, too much nitric oxide produced by our microbiome may cause disease or developmental problems in the fetus."
The study adds to a growing body of evidence that bacteria living in the gut, determined by diet and environment, have a tremendous influence on mammalian health. Stamler imagines nitric oxide may represent an opportunity to manipulate this symbiotic relationship. Just as probiotics are designed to improve digestion, inoculating a person's gut with bacteria to improve nitric oxide signaling is conceivable. "I now think of this therapeutically, as a drug. There are tremendous opportunities to manipulate nitric oxide to improve human health."
While nitric oxide and S-nitrosylation may be a general mode of interspecies communication with broad health implications, it will require additional future research. Will nitric oxide be the only chemical communication channel? "We're basically seeing a new field opening for general strategies of communication," says Stamler. "There will be others."
Story Source:
Materials provided by Case Western Reserve University. Note: Content may be edited for style and length.
Journal Reference:
  1. Puneet Seth, Paishiun N. Hsieh, Suhib Jamal, Liwen Wang, Steven P. Gygi, Mukesh K. Jain, Jeff Coller, Jonathan S. Stamler. Regulation of MicroRNA Machinery and Development by Interspecies S-Nitrosylation. Cell, Feb. 21, 2019; DOI: 10.1016/j.cell.2019.01.037
 
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Remember Fluge and Mella patented an intervention for MECFS using Nitric Oxide?

And of course NO is essential in vasodilation and vasoconstricton. Lots of theories saying poor blood flow could explain our problems. It certainly seems relevant to POTS.

I'm unsure what the links are here but it is tantalising.
 

kangaSue

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Nitric oxide is a gaseous signalling molecule involved in GI motlity too. A nitric oxide synthase deficiency is a common pathology finding in a number of chronic conditions, including gastroparesis which I have a severe case of (idiopathic), and the only med that has helped significantly with the GI symptoms from gastroparesis is a nitrate med. (I don't identify as having ME/CFS though)

The med was prescibed for suspected chronic bowel ischemia (insufficient blood flow to the bowel during the digestion process) even though I had no imaging evidence of blocked bowel arteries. That the med helped significantly suggests something affects my vasodilation/vasoconstriction responses at the intestinal microvascular level, and probably automic dysfunction related (I also have have Autonomic Neuropathy).

(Gastroparesis and chronic bowel ischemia can be one and the same thing with having similar symptom sets)
 

percyval577

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Here another article:

Rao et al 2015 Nitric Oxide mediates Biofilm Formation and Symbiosis in Silibacter ...

IMPORTANCE Bacterial nitric oxide (NO) signaling via heme-nitric oxide/oxygen binding (H-NOX) proteins regulates biofilm formation, playing an important role in protecting bacteria from oxidative stress and other environmental stresses. Biofilms are also an important part of symbiosis, allowing the organism to remain in a nutrient-rich environment. In this study, we show that in Silicibacter sp. strain TrichCH4B, NO mediates symbiosis with the alga Trichodesmium erythraeum, a major marine diazotroph. In addition, Silicibacter sp. TrichCH4B is the first characterized bacteria to harbor both the NOS and H-NOX proteins, making it uniquely capable of both synthesizing and sensing NO, analogous to mammalian NO signaling. Our study expands current understanding of the role of NO in bacterial signaling, providing a novel role for NO in bacterial communication and symbiosis.
The story on nitric oxide may become pretty complex
as a host produces nitric oxide by iNOS in micromolar concentrations to destroy pathogenes, eg bacteria.
 
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ebethc

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Nitric oxide is a gaseous signalling molecule involved in GI motlity too. A nitric oxide synthase deficiency is a common pathology finding in a number of chronic conditions, including gastroparesis which I have a severe case of (idiopathic), and the only med that has helped significantly with the GI symptoms from gastroparesis is a nitrate med. (I don't identify as having ME/CFS though)
how was this diagnosed (ie which test)?
is this caused by bad bacteria (ie can it be solved by lowering bad bacteria, via low carb, etc)? so much is chicken vs egg, w gastro function and bacteria, so it can be hard to tell where it starts..

thx
 

ebethc

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Remember Fluge and Mella patented an intervention for MECFS using Nitric Oxide?

And of course NO is essential in vasodilation and vasoconstricton. Lots of theories saying poor blood flow could explain our problems. It certainly seems relevant to POTS.

I'm unsure what the links are here but it is tantalising.
this is def true for me.... I tried an experiment w citrulline/arginine a few years ago and felt GREAT until I didn't... worst crash BUT I felt like it was worth it b/c it gave me so much insight and convinced me that NO was part of the problem... plus, martin pall's theory is based greatly on NO and his rx for antioxidants has worked well for me, more than any other theory. that's not to say that it's comprehensive, but it's a good piece of the puzzle for me personally.
 

kangaSue

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how was this diagnosed (ie which test)?
Is it gastroparesis you are asking about or a nitric oxide synthase deficiency?
If it's the latter, I don't know. It's not something I've been tested for and and it is only done in clinical studies as far as I am aware.

For diagnosing gastroparesis, there is a breath test available in some countries but it more usually involves eating a small meal with a radioactive tracer then measuring your gastric emptying percent at set intervals over the course of 4 hours (GES - Gastric emptying scintography), if they are following the gold standard protocol.
is this caused by bad bacteria (ie can it be solved by lowering bad bacteria, via low carb, etc)? so much is chicken vs egg, w gastro function and bacteria, so it can be hard to tell where it starts
I think it's usually the case with gastroparesis that the restrictions it can cause to your diet contributes to eventually having a messed up gut bacterial balance but I can't say I have seen any studies into bacterial counts in the early stages of having gastroparesis and GI dysmotility so it's possible that it could be the other way around.
 

Belbyr

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I'm going to start seeing a phycologist about my horrid GI symptoms that keep landing me in the hospital. GI doctors have been horrid...

He has sent me some reading on microbiome and how neurology and digestion are affected. If there is a subgroup I fit in, it is probably that one. (no sudden onset and little to no PEM)