Friday, March 25, 2011

2 The Friday Four

1) Stress affects the balance of bacteria in the gut and immune response

Low stress & bacterial biodiversity:
The key to better health?
ScienceDaily (2011-03-22) -- Stress can change the balance of bacteria that naturally live in the gut, according to new research.

This study funded by the NIH shows that stress dysregulates the immune system, changing the natural flora of one's intestines and leaving people more susceptible to infections such as C. difficile. The more biodiverse intestinal flora is, the healthier one's immune system generally is.

Intestinal bacteria have been linked to diseases like inflammatory bowel disease and asthma, and a future goal of the study is see if changes in gut bacteria is related to such diseases worsening when people are under more pressure.

Comments:

Lyme disease patients are already pretty savvy about taking probiotics inbetween taking antibiotics - but is there something that can be done to diversify the number and kind of bacteria in our guts that would reflect the right balance of helpful organisms? Which combination of organisms is most beneficial to have, and how close are common probiotic blends to this beneficial mix?

Original Source Reference:
Bailey. Exposure to a social stressor alters the structure of the intestinal microbiota: Implications for stressor-induced immunomodulation? Brain, Behavior, and Immunity, 2011; 25 (3): 397 DOI: 10.1016/j.bbi.2010.10.023

2) 'Knowing it in your gut' is real: Cross-talk between human gut bacteria and brain

ScienceDaily (2011-03-23) -- A lot of chatter goes on inside each one of us and not all of it happens between our ears. Researchers have discovered that the "cross-talk" between bacteria in our gut and our brain plays an important role in the development of psychiatric illness, intestinal diseases and probably other health problems as well including obesity.

This study showed that genes linked to learning and memory are altered in germ-free mice and, in particular, in the hippocampus - one of the key brain regions for learning and memory.

"The take-home message is that gut bacteria influences anxiety-like behavior through alterations in the way the brain is wired," said Jane Foster, associate professor in the Department of Psychiatry and Behavioural Neurosciences of the Michael G. DeGroote School of Medicine.

Foster's team has a hypothesis that the state of your immune system and your gut bacteria influence your personality - and in this case, influences anxiety.

Comments:

This reminds me of a video I posted in a Friday Four a while ago that showed personality changes in mice based on whether they had cultivated bacteria or not.

One fascinating thing to consider here is if researchers find out that certain bacterial flora combinations create different psychological states and can be directly implicated in mental illness that new treatments involving probiotics may improve conditions that to date have been treated with psychiatric medications. Perhaps these new treatments will avoid some of the more troubling side effects of anti-depressants and anti-psychotic drugs.


Original Source Reference:
K. M. Neufeld, N. Kang, J. Bienenstock, J. A. Foster.Reduced anxiety-like behavior and central neurochemical change in germ-free mice.Neurogastroenterology & Motility, 2011; 23 (3): 255 DOI:10.1111/j.1365-2982.2010.01620.x

3) Biofilm  reorganization: Back to the theoretical drawing board

Staphlococcus aureus biofilm
"In a surprising new study, researchers using image-analysis methods similar to those employed in facial-recognition software have made a startling discovery that rules out the two main theories scientists had created to explain how bacteria self-organize into multicellular aggregate mounds. The study by researchers from Rice University and the University of Georgia has implications for biofilm research and appears online this week in the Proceedings of the National Academy of Sciences."

What scientists did was make a microscopic movie of Myxococcus xanthus, common soil bacteria, while it was forming aggregates or spore forms with up to 100,000 cells. In this way, the bacteria could survive more easily - just as many other bacteria survive in biofilms to evade antibiotics.

They discovered that the size of the aggregates led to a higher survival rate, and not other factors they predicted such as individual chemical signaling between cells.

So in this case: size matters.

Comments:

More studies on how biofilms form and what can be done to break them up are needed to prevent resistant infections. Studying bacteria and how it organizes itself can tell us more about what makes biofilms work and how to target them for treatment in the future.


4) Breakthrough in delivering drugs to the brain

Alzheimer's plaque
A team of researchers Oxford removed exosomes from mouse dentritic (immune system) cells. Then they attached specific proteins from the rabies virus (not the virus itself) to these exosomes -  proteins which bind to acetylcholine receptors in brain cells.

Then they filled these exosomes with the genetic code, siRNA, and injected them back into the mice.

In doing so, the siRNA got delivered to the mice's brain cells and turned off a gene (BACE1) which is involved in Alzheimer's disease. There was a 60% reduction in the gene's activity.

Comments:

If there is more than one cause for Alzheimer's disease - if it can be treated by using the body's own natural defenses and systems - this could be ground breaking.

Treatment systems similar to these exosome injections could also potentially be used to deliver medicine past the blood brain barrier for other conditions including cancer and infectious diseases.

2 comments:

  1. OC,
    think about this: doxycycline is a second line antibiotic in syphilis, including late stage neurosyphilis.

    NO NEED OF EXOSOMES: pharmaceutical chemists derived lipophilic forms of tetracycline, notably mino- and doxycycline; half a century ago, and these patent-free phantastic ABs cross the blood brain barrier!

    Has the potential of these cheap ABs in late neuroborreliosis / NB been explored enough? Well: in Sweden doxycycline is the AB of choice in NB - but the rest of the world possibly has not taken notice of that?

    Don't dream of "exosomes" etc. Rather try to find out what might be achieved with the "stuff at hand", i.e. doxy.
    I know of two persons who have managed their NB with doxy over more than a dozen years, but probably there are many more...
    chen-men

    ReplyDelete
  2. Chen-men,

    Actually, the use of doxycycline for neuroborreliosis hasn't escaped notice in the United States. Including by the IDSA - which would probably surprise many chronic Lyme disease patients.

    The IDSA 2006 Guidelines for Lyme disease treatment state:

    "Although experience with the use of oral doxycycline for the treatment of meningitis due to Lyme disease is limited in the United States, this drug, administered orally or intravenously, has been used successfully in Europe in adults and in children ⩾8 years of age [174–179]. These studies, however, have included few patients with encephalomyelitis [178]. In one prospective, open-label, randomized trial from Europe [176], patients with neuroborreliosis were treated for 14 days with either oral doxycycline (200 mg per day; n = 31) or intravenous penicillin (∼20 million U per day; n = 23). No significant differences were found in clinical outcome or posttreatment CSF test results between the study groups. In another prospective, open-label, nonrandomized trial from Europe, the rate of improvement in clinical outcome or in CSF cell counts was similar for adult patients treated for 10–14 days with either ceftriaxone (2 g intravenously once per day) (n = 29) or doxycycline (200 mg orally twice per day) (n = 36) [179]. Although duration of therapy has not been systematically compared in studies of acute neurologic Lyme disease, it is noteworthy that 10–14 days of antibiotic therapy has been associated with highly favorable outcomes in both adults [171, 176, 179, 180] and children [178]."

    The IDSA generally doesn't recommend use of doxycycline for late neuroborreliosis, but here you can see that they're okay with using it in early acute neuroborreliosis. I'm not sure those loading doses are high enough, but I'd need to find references to support higher doses.

    And I'm not entirely sure how many ID doctors have used doxycycline to treat late stage Lyme disease. I am aware that some early disseminated cases have received 3-4 months of doxycycline from ID doctors. I know that Dr. Donta will use tetracycline for chronic Lyme disease patients (see his study here: http://www.ncbi.nlm.nih.gov/pubmed/9233665). And I am aware that a number of ILADS doctors have prescribed doxycycline and minocycline for their patients - along with other antimicrobials intended to treat tickborne coinfections.

    There remains a debate in medicine as to whether or not doxycycline and the other -cyclines really are effective at penetrating the blood-brain barrier and if IV ceftriaxone is needed for neuroborreliosis. In general, I've observed that both ID doctors and ILADS doctors will give patients with more obvious serious neurological symptoms IV ceftriaxone and not doxycycline or another -cycline drug.

    The trouble is, even with such treatment, some people will get better but as soon as they stop treatment, the symptoms begin coming back. Where is the treatment end point, then, if this happens? And this is where the controversy begins, because mainstream medicine does not want to keep people on antibiotics forever. So how long is long enough?

    CO

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