Microbiome: hypertension; and atopic dermatitis
Two recent articles found relationships between the gut
microbiome and hypertension (see doi:10.1038/nature24628
); and between the skin microbiome and atopic dermatitis (see DOI: 10.1126/scitranslmed.aah4680 ).
--------------------------
Gut microbiome and hypertension.
Details:
--in mice:
--high salt diet led to increased blood
pressure as well as gut microbiome changes: eg, depletion of
Lactobacillus murinus within one day of the high salt diet
--concomitant high salt diet and
repletion of L. murinus led to a decrease in systolic and normalization of
diastolic blood pressures
--other studies suggest that high salt diet
leads to induction of TH17 cells (T helper 17 cells),
which depends on the gut microbiota
--in this study high salt diet led to led
to pretty specific increases in the mouse TH17 cells, and these
levels decrease with L. murinus treatment
--in humans:
--a systematic review and meta-analysis in
2014 (see Khalesi S. Hypertension 2014; 64: 897) found that probiotics
were associated with decreases in blood pressure
--an exploratory pilot study (a part of
the above mouse study) in 12 healthy male volunteers were given
a high salt diet for 14 days (6 g of sodium chloride/d, equivalent to 2.36
grams of sodium), along with their usual baseline sodium intake, leading
to an overall salt intake of 13.8 g/d:
--in a subgroup
of 8 patients who had ambulatory blood pressure monitoring at baseline and
after the salt challenge (focusing on their night-time readings, to decrease
potential stress-related daytime BP changes):
--nocturnal
systolic and diastolic blood pressures increased with the high salt diet
--the
level of TH17 cells increased with the high salt diet
--at baseline, 7 different gut Lactobacillus species were detected; after
the high salt, 9 of the 10 Lactobacillus populations that were
initially present could no longer be detected (which has been shown in other
studies)
--Lactobacillus is not a dominant member of the human gut
microbiome. in the current study, 5 of the 12 (42%) had at least one
Lactobacillus species at baseline. though other studies in non-Westernized
populations confirm more Lactobacillus in the gut, as is also
the case in newborn infants (which then decreases over time)
Commentary:
--so, in humans,
a high salt diet was associated with increased blood pressure, increased TH17 cells, and reduced
Lactobacillus species in those who had Lactobacillus at baseline
--this was a
small pilot study, which should be replicated in a larger cohort, but the
results do mirror the extensive and
impressive literature in mice. Would be interesting to know if
introducing Lactobacillus species in humans decreased the TH17 cells and also decreased the
blood
pressure...
--it
may mean something that with westernization, there seems to be a decrease in
the apparently healthful Lactobacillus species…???
--------------------------
Skin microbiome and atopic dermatitis
Details:
--in mice:
--mice colonized with S. aureus develop
atopic dermatitis (AD)-like skin lesions
--treating mouse skin with coagulase-negative staph (CoNS), largely S
epidermidis and S hominis, found increased defense against S. aureus
--in humans:
--patients with
atopic dermatitis (AD) frequently have S. aureus on their skin, which is an
important factor in disease exacerbations. And they have decreased ability to
express the antimicrobial peptides (AMPs) of cathelicidins, and b-defensins
--non-AD
patients tend to have more CoNS than AD patients, and these CoNS
have some antimicrobial activity by producing AMPs
--80
patients in this study with AD were tested and the majority who had
positive S. aureus cultures had decreased bacterial diversity.
--and,
many of the CoNS species in AD patients did not have antimicrobial
activity, suggesting that it was the specific strain and not the species
identity that predicted antimicrobial function
--a
small study of 5 people who had AD and were S. aureus culture-positive: rare
clones of S. hominis or S. epidermidis were found with antimicrobial activity,
but when these rare isolates were grown in culture to produce the
normal colony count of non-AD patients’ skin, a single application to these 5
people dramatically decreased S. aureus abundance. And doing this
process in mice repeatedly for one week led to complete elimination of S.
aureus.
Commentary:
--patients with
AD are frequently colonized with S aureus, and this colonization is associated
with disease exacerbations. In this study, patients with AD had more S.
aureus present when their commensal CoNS did not have antimicrobial
activity (which was typically found). So, AD was basically associated with
decreases in quantity of CoNS as well as dramatic decreases in functionality
(ie, most had no antimicrobial effect)
--But, finding
and culturing the few CoNS which had antimicrobial activity in AD patients, then
reintroducing the subjects' own functional CoNS colonies back to the skin as a
single application, dramatically reduced their S. aureus colonization.
--Unclear why
the AD patients who had significant CoNS on their skin had a dysfunctional
CoNS lacking antimicrobial activity against S. aureus. Did the dysfunctional
CoNS lead to S. aureus colonization? did long-term exposure to S. aureus
lead to dysfunctional CoNS? Did some other, perhaps environmental factor lead
to both dysfunctional CoNS and S. aureus overgrowth?
--one advantage
of the above approach of introducing functional CoNS back to the skin is
that it avoids using broad-spectrum antibiotics in AD patients as are often
used, and these antibiotics might further distort the microbiome (and further kill
CoNS strains), instead of replenishing the microbiome with
physiologically-active CoNS. But, would it be as effective if generic CoNS
strains were applied topically? Ie, do they need to be harvested from the
individual patient, grown in vitro, then transferred back to the skin?
--as a brief
review of the current knowledge about the skin microbiome: the skin
microbiome has not been studied as well as the gut microbiome, but there is
evidence that it interacts with the gut microbiome; and the skin microbiome
manufactures and metabolizes steroid hormones, peptide neurohromones and
neurotransmitters. It can have stress-induced increases in Substance P, which
is linked to eczema, acne, and barrier dysfunction. In germ-free mice, the
lack of skin commensal bacteria affects normal immune responses, especially
cytokine production. In healthy
teenagers, Acinetobactor on the skin is associated with IL-10 expression
in peripheral blood, reflecting a systemic effect of surface bacteria. In North
Karelia, those people who are in the more westernized region have more
eczema (see http://gmodestmedblogs.blogspot.com/2016/08/microbiome-and-type-1-diabetes-etc.html ,which also reviews a study from North Karelia), and have less abundance
and diversity of Acinetobacter on the skin and nasal epithelium. The
environmental factors affecting the skin microbiome are also less
well-understood as compared to the gut, but the skin microbiome tends to change
more easily over time, is influenced by exposure to pets, person-to-person
contact (including shared cellphones), and (likely) ambient temperature,
ventilation, co-occupancy, humidity, environmental contact, air quality, UV
light, pH, and the skin's lipid content. also, the skin microbiome can be quite
different in different areas of the body of the same person, and microbiomes
can be successfully transplanted from one area of the body to another. In
addition, oral probiotics can influence the nasal microbiome (see Prescott SL.
World Allergy Organizataion J 2017; 10:29, or go to https://waojournal.biomedcentral.com/articles/10.1186/s40413-017-0160-5 ).
so, the point of these microbiome studies is not to push for
probiotics or even skin microbiome transplants, but to point out a few things:
--the various human microbiomes (gut,
lung, vaginal, skin, etc) seem to serve as important
intermediaries between the environment and health/disease
--there are important ways to optimize the
health of these microbiomes: minimize antibiotic use and, in particular,
broader spectrum antibiotics. also, as per prior blogs (see below), diet,
exercise, healthy weight, decreased stress, better quality sleep (and, no
doubt, more) can have pretty profound effects on the microbiomes (best
documented for the GI microbiome)
--and (for the GI microbiome) though
probiotics or fecal transplants do seem to have some positive effects, it
seems that these effects would pale in comparison to these above interventions
of improving lifestyle and avoiding antibiotics:
--partly because our
understanding of the various microbes in the gut is undoubtedly far from
complete and our understanding of the likely complex interaction between the
different species is even further from complete,
--partly because we are making
really small changes in the composition of the gut (the absolute numbers of
bacteria in the gut is staggering, per prior blogs, and the number of
"good" bacteria introduced with probiotics is miniscule, and no
one knows what is the optimal composition and relative potencies of
the different bacteria introduced (and the current preparations in the
marketplace vary dramatically from one to another),
--and in terms of fecal
transplants, one concern is also transplanting potentially serious microbes
from one person into another that are hiding in the gut (and these microbes
might take years to create disease: are we getting short-term benefits but
potentially very serious long-term diseases???)
prior
blogs of note:
http://gmodestmedblogs.blogspot.com/2015/10/gi-microbiome-in-little-kids-and.html for a Canadian study associating the GI microbiome in little kids and asthma
http://gmodestmedblogs.blogspot.com/2014/11/gastric-acid-suppression-and-microbiome_23.html shows that gastric acid suppression leads to changes in the gut and also in the
lung microbiomes. ??predisposes people to pneumonia
http://gmodestmedblogs.blogspot.com/2017/10/mediterranean-diet-helps-nafld.html documents the data on the microbiome and NAFLD, as well as a study showing
that the Mediterranean diet decreased hepatic steatosis
http://gmodestmedblogs.blogspot.com/search/label/microbiome
for the array of many many blogs on the microbiome, including the association
between antibiotics and colorectal adenomas, dramatic microbiome changes by
artificial noncaloric sweeteners (leading to weight gain, glucose
intolerance, ...), association with asthma and allergic/immunologic disorders,
the effects of diet/exercise/travel/sterss/poor sleep on the microbiome, and
the huge and potentially devastating longterm microbiome changes with
antibiotics.
If you would like to receive regular emails with these blogs, please let me know at gmodest@uphams.org
Comments
Post a Comment
if you would like to receive the near-daily emails regularly, please email me at gmodest@uphams.org