Gut Microbiome Varies Hour to Hour, Month to Month - Intraindividual shifts over time may explain why drugs don't work the same in everyone, MedPage Today, by John Gever, Contributing Writer, May 4, 2023
While not specific to PCa, this contribution to the understanding of the complex nature of the microbiome has wide-ranging implications for our health. In particular, as the highlighted section from the MedPage article reproduced below implies, it might well help explain some inconsistencies in clinical trial results, as well as n=1 variations in individual responses to the same treatments, meds, and various dietary/lifestyle interventions.
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CHICAGO -- Composition of a person's intestinal microbial population differs from morning to night and from one month to the next, researchers found.
Analysis of more than 18,000 timestamped stool samples collected worldwide indicated that centered log-ratio values (a measure of relative abundance) for different bacterial phyla and families commonly found in the gut microbiome varied substantially over the course of a single day, and also over a full year, according to senior investigator Amir Zarrinpar, MD, PhD, of the University of California San Diego.
Populations of some phyla, such as Actinobacteriota, tended to peak in the afternoon and evening. Others, such as Proteobacteria, were more abundant in the morning, with troughs later in the day, Zarrinpar said at a press conference held in advance of the annual Digestive Disease Week conferenceopens in a new tab or window, to be held here starting Saturday.
Thus, at one point in the day certain types of bacteria may predominate but a wholly different composition may appear a few hours later. "More than a third" of phyla analyzed showed some degree of diurnal cycling after adjusting for confounding variables, Zarrinpar said.
Similar patterns were seen across seasons: Proteobacteria hit their annual zenith in the summer and a winter trough, while a massive peak was found for Bacteroidota in late autumn and a nadir in late spring. The time plot for Verrucomicrobiota showed a double peak, in spring and again in the fall at a similar level.
Zarrinpar said seasonal variations in temperature, humidity, and other "environmental factors" likely drive these changes, with different types of bacteria responding in their own peculiar ways.
With regard to diurnal cycling, he cited such influences as "nutrient and water availability and sleep" as important factors.
He also speculated that these previously unsuspected shifts in gut bacteria might help explain why people don't all respond to a particular drug in the same way, insofar as the microbiome is important in metabolizing them (and can affect organ function in other ways as well).
"As physicians and as scientists, we always wonder why certain patients respond more robustly to some medications than others. I think that in terms of performing clinical trials, it's important to remember that -- especially if it's a wide-ranging, multiyear study -- that perhaps there may be seasonal variations in response to a drug, and if so, it may be affected by something [like] the relationship of the microbiome, the host immune system, or post-metabolic processes," Zarrinpar said at the press conference. (emphasis added.)
"For example, an interesting thing we've thought about is that patients' responses to COVID vaccines differs by what time of day they receive the vaccine. Certainly since the microbiome is a tremendous influencer of immune response, we do wonder whether these variations [in microbiome composition] have a role in something like vaccine response."
Microbiome variations might also account for seasonal increases and decreases in susceptibility to infections, he said.
He cautioned that "it's too early" to conclude definitively that microbiome variation drives drug and vaccine responses, but it clearly deserves more study.
Stool samples were collected as part of the American Gut Project, a "citizen science" program in which individuals voluntarily submit dry-swab samples through the mail. Almost 100,000 have entered the project's database so far -- "primarily from Western countries" and in the Northern Hemisphere, according to Zarrinpar -- mostly collected from 2013 to 2019. The 18,219 included in the current study were those with day and time of collection recorded, and with at least 200 bacterial counts per sample. No more than 10 samples from any individual were allowed, and those from children or adolescents were excluded.
Zarrinpar also noted at the press conference that the data show some regional and ethnic differences in the diurnal cycling patterns. Those data were not presented in detail or included in the abstract published before the conference.
He also indicated that an important direction for future research is to examine whether the diurnal and seasonal variations correlate with individuals' health status.
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Here are links to the 1) MedPage Article, 2) The Digestive Disease Week Press Release, and 3) a paper describing the Citizens Science Microbiome Research Project:
1) Gut Microbiome Varies Hour to Hour, Month to Month - Intraindividual shifts over time may explain why drugs don't work the same in everyone, MedPage Today, by John Gever, Contributing Writer, May 4, 2023
The human microbiome is a classic case where the more we learn about it, the more we come to realize how little we really understand about its complexity and many impacts on our health.
Live to Learn & Stay S&W, Ciao - K9 terror
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Food for thought, thanks for posting. Interested as I have noticed a seasonal PSA behaviour. Each year, 4 years now, November and December offer PSA surprises. Vitamin D, a prime seasonal suspect, must be ruled out as I heavily supplement all year round.
It's often those "patterns that connect" which illuminate new pathways for treatment. Your super-active analytical mind has seen one that might be related to the microbiome's seasonal variation. If I can ever get back on a regular treatment regime, I'll be looking for similar ones. Some proponents of dietary interventions go so far as to suggest that we should tailor our diets to our personal genome's geographic homebase and then only eat plants when they would be in season there. Validity of that will never be tested, so for me, it just remains an interesting notion for consideration. However, when looked at in the context of this paper's findings, it might actually make sense . . . logically - in that it would be feeding the gut flora with the sort of different nutrients to support such short and longer-term variations in gut biodiversity.
BTW, I got my boobie RT yesterday and can now get back on my bical dosing experiment. I also had a blood draw for a basic male hormone panel as a new start-from baseline. As I've been on tamoxifen for about 60 days, it will also show what that is doing to E2. I had planned to add 5-ARi dutasteride and adjust the bical to see what benefit I might get from that combo at time-adjusted dosages. With the recent introduction of tamoxifen, I now have a potential third player for the dosing tests - i.e., @ 10 mg on a weekly basis or a half-tab 3 x per week it might provide some E2 control - if needed. (Friedman seems to think E2 alpha is the bad player since it promotes Bcl-2 - and, unfortunately, tamoxifen knocks down both E2 alpha and the (supposedly) beneficial E2 beta.)
Hope all is well with you and yours. Stay S&W. Paz - Kaptin K9
Not the only thing that varies on a circadian & seasonal basis.
Hormones:
- melatonin, of course. (not easy to get it tested at the peak - lol)
- pituitary hormones are also tied to the circadian cycle:
.... luteinizing hormome [LH], which stimulates Leydig cell production of testosterone
.... ACTH which tells the adrenals to produce cortisol
.... FSH
.... growth hormone (peaks around 2-4 am)
.... TSH - tells thyroid to produce hormones
.... etc.
- testosteone - max around 7 am
- cortisol - similar to T - although some in stressful jobs might say it gets higher as the day progresses.
- & so on
- hormonal vitamin D (1,25-D) can vary by season, since the 25-D reservoir depends on sunlight exposure
We manipulate the above with supplements & drugs.
Seasonal variations:
- we sleep an hour longer in winter (if permitted)
- there may be an instinct to gain weight in summer, to tide one through the winter, although we can get summer foods all through the year now - so some experience weight gain in winter.
Do we pay enough attention to the timing of blood tests, medication dosing, what to eat when?
Patrick, Thanks for adding a dozen more layers of complexity. The old saying about 'when you find yourself in a hole, the first thing to do is stop digging' seems to not apply in the case of human metabolism, immunity, cancer heterogeneity, and the microbiome. Only by forever digging do we ever find the hidden treasures along the way.
BTW, shouldn't you be glued to telly taking in all the pomp and circumstance of the coronation?
The NY Times today had as much coverage as I could take. Half of the UK aren't that interested (the younger half) - and the Commonwealth (ex-colonies) seem to want to break ties (with reparations.) The king will have his work cut out for him, keeping the family business together.
The most interesting story was about the house Charles owns in Transylvania. In the middle of nowhere, set back in time. He has been going there every year since he bought it. What does that reveal about him? He's my age. Perhaps he should retire now that he has finally made it to king. Move to Transylvania,
You can rent his getaway for $200/night (meals included.) Seriously.
The King and Count both hanging in Transylvania. $200 a night with meals (Bat Stew?) in the middle of nowhere sounds like my dream getaway!
While his views are often controversial, I've always like the new king for his willingness to engage the modernist crap-architecture, suggesting many (most?) of them have no regard for the surrounding context of their serial "masterpieces". I like the coined phrase "name-brand" architecture, as commissions for significant buildings in the public sphere went/go to that award-winning cadre of "look-at-my-creation" architects. We should be teaching architecture using the principles outlined by Christopher Alexander and NOT a bunch of esoteric ego-driven "master designers" . . . JMHO, of course.
My architect wife says that the value of an architectural design is to be assessed when the building gets old. Buildings like people get old. Very few look better than in their youth, the vast majority look worse.
It makes me wonder about "super responders" and whether their microbiome is significantly different than others.. Why do some develop resistance earlier?...is it all just disease severity and genetic mutations or does a poor microbiome play a role?? We have discussed Akkermansia muciniphilia and the immune system... some guy wrote a post on it here a while back:
I take abiraterone which helps to build Akkermansia muciniphilia levels... I also take Dr Langer's Ultimate 16 Strain Probiotics with FOS to maintain my microbiome and help the abiraterone.
The real question is how does the microbiome play a role in Prostate Cancer?? Can an attack and defend strategy be developed? Will fecal transplant via enemas become a part of the treatment plan ??
Fish - Did you catch any fish with that unattended rod & reel on Friday? Or did a big fish catch a rod and reel?
I'm reading a book this book, Curable: How an Unlikely Group of Radical Innovators Is Trying to Transform our Health Care System by Travis Christofferson. (I also read his earlier book, Tripping over the Truth: How the Metabolic Theory of Cancer Is Overturning One of Medicine's Most Entrenched Paradigms.)
Curable, for better and worse, is a case on Moneyball (see Kahneman & Tversky - Thinking, Fast and Slow) meets modern medicine. Along the way, he describes the long history of resistance to fecal implants and the amazing success of fecal implants to cure C. diff. - even when done via YouTube instructional videos in the face of that resistance. Is there a role for fecal implants for PCa? How would we know unless someone is testing for possible efficacy. The very simple do-it-yourself procedure is described, but the key would be finding the right donor; i.e., what would a perfect fecal profile look like?
He also discusses the proven efficacy of both metformin and lipophilic statins for cancer prevention and treatment - and the refusal of mainstream medical oncologists to endorse the use of either.
Of special interest to me was his very insightful story about lab research with rats having cancer cells injecting into their portal veins (which drains directly into the liver), then waiting five months, and removing their livers - to find them healthy and cancer-free. They repeated the experiment, but starting at three months they made incisions across the bellies of the rats. These incisions were repeated weekly with no purpose other than to release wound-healing factors on the distant cancer cells. When they looked at the rat's livers at five months this time, they were filled with tumors - in 100% of the animals; i.e., all of the rats that suffered the trauma and resulting inflammation and healing actions developed tumors. I now have a fourth possibility for BCR#2, the surgical trauma of the AUS replacement.
All books mentioned above are good reads for a man who has time to go fishing. I have them all in ePub format if you have an eReader. Have a good week. Ciao - K9
PS as for you PM reveal, I guess I should check to see how my content is being "curated".
The story of the way that fecal transplant happened for C. diff. was that a wife of a patient who could not be cured with antibiotics decided that a poop transplant might help...I believe she was a nurse, so she took a dump in a blender (no Paper) and added warm water, put it in an enema bag, and gave it to hubby... after a number of infusions, the C. diff was resolved...
Yes, inflammation is one of the horsemen, so repeated exposure via cutting did not help...
As for the fish, it was a day of truce, so no one engaged on either side...I still have the pole, but no one ended up in the icebox that day either...
As for PM, I just sent you a revelation that was revealed to me... You will not be surprised... I am sure of that response...
That's the right story. Who would thought someone else's poop could save your life - and embarrass the health care community in the process. It is a prime example of superior patient advocacy doing what is necessary when the docs throw in the towel. Leave no medical stone unturned.
As for the PM. I'm never surprised on that topic anymore.
Have a nice week - Go catch yourself some fish. I'm going to chase me some fast cars. Paz - K9
Belt sander over head is some work out... being careful... but that seems to be the best for removal... Locum tenens is chasing my wife... looks like the summer got a whole lot busier due to their pursuit... I did find 45 minutes for fishing... the melding with nature is good for my stress...
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