reply kl 13.51 fredag 12-7-2019
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To Professor Olivier Piguet - The Olfactory Sense
- emailed Fredag 12-7-2019
Prof Piguet is an NHMRC Senior Research Fellow and Professor of Clinical Neuropsychology. He is the co-director of FRONTIER, the frontotemporal dementia clinical research group and the director of the Memory Program of the ARC Centre of Excellence in Cognition and its Disorders.
Good Day Professor Piguet,
I watched you on a Netflix show, “Ask the Doctor”, episode “The Senses”, season 1.
I have reason to believe the sense of smell is diminished in Parkinson’s Disease and other neurological conditions as a result of dysbiosis. Joy Milne can smell Parkinson’s which leads me to believe, like a case of Strep Throat which can be smelled from an over abundance of Streptococcus pyogenes, a dysbiosis exists in PD patients.
An out of balance microbial soup allows an overgrowth of one or more, therefore, a diminished population of another. If the diminished population can be supported or re-established symptoms of the disease (tremors, anosmia, cognitive decline, breathing difficulties) could be managed better. There is a possibility that perhaps the congruence of dysbiosis leads to mis-folding of Beta Amyloid Peptides, Tau Proteins or Alpha-synuclein Protein 1, Could these tangled accumulations NOT exist if dysbiosis were treated?
It is well known drugs interact with body function. Morphine binds to an opiate receptor to have its effect. When the opiate receptor is located on sphincters in the lower digestive system, the sphincters relax and a side effect occurs - constipation.
Nature ran an article in March 2018 2, how non-antibiotic pharmaceuticals could affect the gut microbiome. The Microbiome is not only in the gut, it is on the skin, in the mouth, in epithelial tissue and in the nasal passages as well. The sense of smell is highly relevant to the communities of microbes within the olfactory system. An early warning sign of PD, is the loss of the sense of smell.
Prevotella species help the breakdown of protein and carbohydrate foods in the rumen of cattle and sheep. Studies have shown patients with Parkinson’s disease have less bacteria of the Prevotellaceae family in their gut than control subjects 3. Why? We don’t know.
When humans eat flavonoids, this type of polyphenol is beneficial to the human brain and vascular function.4 Before the human body absorbs a flavonoid, intestinal enzymes or colonic microflora MUST hydrolyzed them 5. If the colonic microflora is missing, the health benefits and vascular protections are missing.
The roots of a legume plant secrete flavonoids to help gram negative, motile, non-sporulating rods of diazotrophic bacteria known as Rhizobia have a symbiotic relationship and fix nitrogen for the plant to have in a usable form. 6
Is there a possibility, the Nitric Oxide, humans need is regulated by a microorganism like in the legume plant? Perhaps the lack of this microbe in humans stiffens not only the blood vessels but the human fascial system, whereby making neurotransmission and neuromodulation inept. Cycling, Boxing, Singing and Dancing all promote more Nitric Oxide production in vivo. If I were a protein, overtime, I would mis-fold and mis-behave, under these circumstances, without the proper balance of microbes.
I leave you with excerpts from an article written by Miro Mannino. There have been many whom have written about the Island of Guam and lytico-bodig disease like Oliver Sacks.
All my best for your research. Hope you can used some of mine.
Allissa Harter from Iowa, Living in Sweden
Long studied, now disappearing disease (excerpts only)
by Miro Mannino
Lytico-bodig is the local name for a complex of neurological diseases (or diseases that affect the nervous system) on Guam that resembles amyotrophic lateral sclerosis (ALS or Lou Gerhig’s disease), Parkinsonism-Dementia (PD) and possibly Alzheimer’s disease.
Although lytico-bodig are worded together, they actually represent two different diseases. The term “lytico” comes from the Spanish word paralytico which means weakness. “Bodig” comes from the Spanish word bodega, or warehouse. Lytico patients have ALS symptoms, while patients with Bodig have symptoms that resemble PD.
Because of its occurrence in a relatively unique and isolated population, lytico-bodig has been widely studied by various groups of researchers in the hopes of finding its cause and possible cures.
Now known formally as ALS-PD complex of Guam (ALS-PDC), its prevalence in the 1950s and 1960s brought a sense of immediacy to working on Guam as patients passed away from the disease. The major research efforts sought to answer the question of whether lytico-bodig is a genetic or hereditary disease, or one caused by some environmental factor or factors? Although numerous theories were brought forward, there is still no definitive set of causes or cures. With advances in medical technology, strides have been made toward understanding lytico-bodig clinically, however, only few have studied its social or cultural impact on the Chamorro people. Although reports of neurological disease resembling lytico-bodig among the Chamorros occurred as far back as the early 1800s, formal study of the disease would not take place until more than a century later.
At its peak in the 1950s, lytico-bodig became the leading cause of death for Chamorros, affecting some 420 per 100,000 Chamorros, at a ratio of 2:1 males to females. ALS was seen more in Chamorros, while PD was seen in both Chamorro and Filipino natives. According to Chris Plato, et al., the incidence of ALS peaked from 1950-1954 in both males and females, but by the late 1950s, the incidence of ALS began to decline. Also, the incidence of PDC in males peaked from 1960 to 1964, and then declined steadily until 1980. The incidence of PDC in females peaked in 1970 to 1974, then rapidly declined in the early 1980s.
Another symptom which seems to be associated with ALS/PDC is linear retinal epitheliopathy, which is a disorder of the eye. The retinal epithelium is the pigmented layer of the retina at the back of the eye that anchors photoreceptors, or the cells that sense light and help with vision. There are no symptoms except for unusual tracks that appear in the retinal layer, but it seems to appear in half of Guamanian Chamorros with ALS and PDC and to precede the onset of the disease.
Probably the most well-known proposed cause of lytico-bodig involves neurotoxins in cycad seeds. In the 1960s, early researchers Leonard Kurland and Donald Mulder postulated that poisons in cycad seeds, ingested over time, possibly caused the disease on Guam. Unlike other Pacific islands, the Chamorros on Guam would leech the seeds of the false sago palm (Cycas micronesica, or fadang in Chamorro) to remove the poisons and then ground them into flour for baking.
In the early 2000s, the cycad toxin theory was brought up again with Paul Cox and Oliver Sacks who observed a decline in lytico-bodig that paralleled a decline in the fruit bat population on Guam. They proposed that while cycad processed into flour was not toxic enough to produce lytico-bodig, there may be other elements in the Chamorro diet that could magnify the effects of the neurotoxin. Eating fruit bat (Pteopus ariannusmariannus, or fanihi in Chamorro), for example, a local delicacy, might contribute to the possibility of the disease. The scientists suggested that fruit bats that eat the cycad accumulate the toxins in their tissues but may not themselves be affected by the toxins.
However, if people ate enough of the fruit bats over the course of their lifetime (perhaps beginning in childhood), the toxins could accumulate in their bodies and eventually cause the disease. Cox also suggested that the presence of cyanobacteria in cycads which could produce BMAA naturally, may also be considered a possible cause. Cox and his colleagues also reported that BMAA was found in ALS and PD patients on Guam.
1) https://ghr.nlm.nih.gov/gene/SNCA It is unclear how alterations in the SNCA gene cause Parkinson disease. This condition involves the selective death or impairment of neurons that produce dopamine. Misfolded or excess alpha-synuclein proteins may cluster together to form Lewy bodies and impair the function of these neurons in specific regions of the brain. Lewy bodies may disrupt the regulation of dopamine, which allows dopamine to accumulate to toxic levels and eventually kill neurons.
2) Nature volume 555, pages 623–628 (29 March 2018)
“Extensive impact of non-antibiotic drugs on human gut bacteria”
Lisa Maier, Mihaela Pruteanu, Michael Kuhn, Georg Zeller, Anja Telzerow, Exene Erin Anderson, Ana Rita Brochado, Keith Conrad Fernandez, Hitomi Dose, Hirotada Mori, Kiran Raosaheb Patil, Peer Bork & Athanasios Typas
3) Patients with Parkinson’s disease have clear changes in their gut microbiota
A study carried out at the University of Helsinki indicates that microbes in the gut and mouth could provide new perspectives on the onset of Parkinson’s disease, particularly as they have long been suspected to play a part in the disease process.
Recently, microbial inhabitants of the human body have been connected to several health problems, including Parkinson’s disease and other neurological diseases.
In her doctoral dissertation, Velma Aho investigated the potential associations of Parkinson’s disease and human microbiota in the mouth, nose and gut, and examined the tools used to compare their abundance. Aho’s findings supported an observation according to which patients with Parkinson’s disease have less bacteria of the Prevotellaceae family in their gut than control subjects.
Prevotella species are among the most numerous microbes culturable from the rumen and hind gut of cattle and sheep, where they help the breakdown of protein and carbohydrate foods.
my Letter to Velma Aho. She answered April 17, 2019 “I must admit I don't know anything at all about the relationship of Prevotellaceae and nitric oxide. I have primarily focused on gut microbiota analyses, and a quick literature search of Prevotella and NO seems to mainly give hits related to oral microbiota. The oral species and strains tend to be different from the ones in the gut, so it's difficult to know how similar their metabolism etc would be. Overall, what the gut Prevotella species are actually doing seems quite unclear to me based on the literature I've found so far, so there's a lot of research to be done regarding that. But I think I will try to look more into the Prevotella and NO literature in the future, since this is something I haven't read about at all. So, unfortunately I don't really have an answer for you, but it's an interesting question, so thank you again!”
4) Professor Jeremy Spencer
A major output from the group has been to help define the paradigm-changing concept of how flavonoids and other polyphenols act via non-antioxidant mechanisms of action in vivo to mediate bphysiologically/clinically significant benefits on human brain and vascular function. His group have defined how a number of flavonoids/polyphenols and their metabolites exert specific interactions within ERK and PI3 kinase/Akt signalling pathways, leading to increases in the expression of neuroprotective and neuromodulatory proteins and an increase in the number of, and strength of, connections between neurons. Furthermore, they have detailed effects on the vascular system, which may lead to enhancements in cognitive performance through increased brain blood flow and an ability to initiate neurogenesis in the hippocampus.
5) Oxid Med Cell Longev. 2009 Nov-Dec; 2(5): 270–278.
Plant polyphenols as dietary antioxidants in human health and disease
Kanti Bhooshan Pandey and Syed Ibrahim Rizvi
Department of Biochemistry; University of Allahabad; Allahabad, India
Correspondence to: Syed Ibrahim Rizvi; Email: moc.liamg@ivziris
Diazotrophs are bacteria and archaea that fix atmospheric nitrogen gas into a more usable form such as ammonia. Cyanobacteria—there are also symbiotic cyanobacteria. Some associate with fungi as lichens, with liverworts, with a fern, and with a cycad.