Poor absorption of Vitamin D is strongly related to type of gut bacteria – Dec 2020

The potential role of vitamin D supplementation as a gut microbiota modifier in healthy individuals

Sci Rep. 2020 Dec 10;10(1):21641. doi: 10.1038/s41598-020-77806-4.
Parul Singh 1, Arun Rawat 1, Mariam Alwakeel 2, Elham Sharif 3, Souhaila Al Khodor 4

 Download the PDF from VitaminDWiki

Non-Responders = did not respone to >20 ng/ml after 50,000 IU weekly for 12 weeks

Vitamin D deficiency affects approximately 80% of individuals in some countries and has been linked with gut dysbiosis and inflammation. While the benefits of vitamin D supplementation on the gut microbiota have been studied in patients with chronic diseases, its effects on the microbiota of otherwise healthy individuals is unclear. Moreover, whether effects on the microbiota can explain some of the marked inter-individual variation in responsiveness to vitamin D supplementation is unknown. Here, we administered vitamin D to 80 otherwise healthy vitamin D-deficient women, measuring serum 25(OH) D levels in blood and characterizing their gut microbiota pre- and post- supplementation using 16S rRNA gene sequencing. Vitamin D supplementation significantly increased gut microbial diversity. Specifically, the Bacteroidetes to Firmicutes ratio increased, along with the abundance of the health-promoting probiotic taxa Akkermansia and Bifidobacterium. Significant variations in the two-dominant genera, Bacteroides and Prevotella, indicated a variation in enterotypes following supplementation.
Comparing supplementation responders and non-responders we found more pronounced changes in abundance of major phyla in responders, and a significant decrease in Bacteroides acidifaciens in non-responders. Altogether, our study highlights the positive impact of vitamin D supplementation on the gut microbiota and the potential for the microbial gut signature to affect vitamin D response.

.Discussion - clipped from PDF

In this study we aimed to characterize changes in the gut microbiota of vitamin D-deficient female volunteers following 12 weeks of vitamin D supplementation. In addition, we wanted to assess whether any characteristics of the gut microbiota were linked with the response to vitamin D supplementation. We found that vitamin D supplementation increased the overall diversity of the gut microbiota, and in particular the increased the relative abundance of Bacteroidetes and decreased the relative abundance of Firmicutes. A high ratio of Firmicutes to Bacteroidetes has been correlated with obesity 51 and other diseases 52-54; while conversely a prebiotic intervention that decreased the Firmicutes to Bacteroidetes ratio resulted in improvements to gut permeability, metabolic endotoxemia and inflammation55. Alongside the results of a recent pilot study29, our data solidify the proposed link between Vitamin D supplementation and decreased Firmicutes to Bacteroidetes ratio, which is associated with improved gut health54.

In addition to improving the Bacteroidetes to Firmicutes ratio, our data show that members of Verrucomicro- bia and Actinobacteria phyla also increased in abundance following vitamin D supplementation. Akkermansia muciniphila is the only representative of the phylum Verrucomicrobia in the human gut,56,57 and helps maintain host intestinal homeostasis by converting mucin into beneficial by-products58. The abundance of A. muciniphila negatively correlates with body mass 59,60 inflammation 61 metabolic syndrome 62 and both type 1 and type 2 diabetes 60,63. Our analysis also showed a significant increase in the abundance of Bifidobacterium which is an important probiotic with a wide array of benefits to human health64, as well as playing a role in folate and amino acid production65. Accordingly, using PICRUSt predictive functional analysis, we predicted an increased in genes involved in folate production and biosynthesis of several amino acids following vitamin D supplementation.
Alongside characterising individual taxa, Wu et al. clustered fecal communities into two enterotypes distinguished primarily by the levels of Bacteroides and Prevotella, and found that vitamin D intake was negatively associated with abundance of the Prevotella enterotype, instead being strongly positively associated with the Bacteroides enterotype66. In line with this, we found that vitamin D supplementation favoured a Bacteroides- dominated enterotype over Prevotella. This is potentially important as several studies indicate Prevotella as an intestinal pathobiont: high levels of Prevotella spp. have been reported in children diagnosed with irritable bowel syndrome67; while the expansion of Prevotella copri was strongly correlated with enhanced susceptibility to arthritis68.Taken together, our results make a compelling argument that vitamin D supplementation modulates the gut microbiota composition and diversity towards a more beneficial state—a previously undescribed benefit of vitamin D.
At present, the mechanism underlying vitamin D regulation of the gut microbiota is not clear. One possibility is that, following absorption in the small intestine1, vitamin D could impact gut microbial communities via indirect systemic mechanisms; for example, the vitamin D receptor (VDR) is highly expressed in the proximal colon and acts as a transcription factor regulating expression of over 1000 host genes involved in intestinal homeostasis and inflammation, tight junctions, pathogen invasion, commensal bacterial colonization, and mucosal defense70, including the defensins, cathelicidin, claudins, TLR2, zonulin occludens, and NOD269,70. Interestingly, there is some recent evidence of the cross talk between the gut microbiota and VDR signalling affecting host responses and inflammation, and this appears to be bidirectional9. Intestinal VDR expression has been shown to regulates the host microbiota to mediates the beneficial effects of probiotics71,72 and vitamin D treatment72-75. Similarly, probiotics and pathogenic bacteria have been also shown to modulate VDR expression, with the former increasing76, and the latter decreasing77, its expression.

Alternatively, or alongside such systemic mechanisms, growing evidence suggests that vitamins administered in large doses escape complete absorption by the proximal intestine 78, and so might then be available to directly modulate the distal gut microbiome. Whether this is the case for the vitamin D remains to be investigated; however, such a mechanism might account for the differences in microbiota change seen in various studies employing high versus low dose supplementation protocols.

Interestingly, in our study microbial functional potentials inferred using PICRUSt indicated that vitamin D supplementation elevated pathways associated with the metabolism of amino acids, cofactors, vitamins, and lipids, including steroid biosynthesis and fatty acid elongation. This could be important as adequate concentrations of lipids, bile salts and fatty acids are required for incorporation of fat-soluble vitamin D into mixed micelles, as a prerequisite for its absorption 79,80. Thus, increased abundance of bacterial genes related to lipid and fatty acid metabolism post supplementation could indicate increased vitamin D bioavailability and absorption in the gut81.
While the benefits of vitamin D supplementation in deficient/insufficient level individuals are clear, there are a sub-group of people in which even high-dose oral vitamin D supplementation has been shown to be ineffective. A secondary aim of this study was to assess whether the microbiota in these individuals could be associated with their non-responder status. Lower levels of baseline Bacteroides acidifaciens in non-responders combined with an additional depletion post-supplementation suggest that this bacterium may be linked with response to vitamin D supplementation. Bacteroides acidifaciens has previously been proposed as a “lean bug” that could prevent obesity and improve insulin sensitivity82. It is also one of the predominant commensal bacteria that promote IgA antibody production in the large intestine. Thus, we hypothesize that the vitamin D supplementation promotes the ‘farming’ of good bacteria in order to maintain immune-microbe homeostasis.

While results from this study are promising and warrant more research, it is worth noting that our study has few limitations. Firstly, we did not have vitamin D sufficient controls to observe the impact of vitamin D supplementation in comparison with the deficient subjects. Secondly, addition of a placebo group would minimize the potential effects of non-treatment factors. Lastly, experimental studies with larger cohort needs to be undertaken to have sufficient representation of study responders/non-responders to confirm the finding of the present study.

In conclusion, vitamin D supplementation of deficient/insufficient otherwise healthy females changed the composition and diversity of the gut microbiota, eliciting a beneficial effect by improving health-promoting taxa along with clinical biomarkers for kidney and liver function. Our study also provides a proof-of-concept that the gut microbiota is informative in examining individualized responses to vitamin D supplementation, presenting a rationale for planning future clinical trials that focus on the inter and intra individual variation using multi- omics approaches such as genotyping, transcriptomics and proteomics.

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VitaminDWiki has been investigating why some have poor response to Vitamin D

Reasons for low response by vitamin D level in the blood contained the following Dec 2020
~ 50% of all people have a low response to vitamin D3
~ 10% of all people have a ZERO response to a LOW dose

Occurence	Reason for low response	Typical % extra Vit D needed	Comments
Common	Excess BMI/weight	150%	Obese need 2X to 3X more
Common	Vitamin D supplement was not taken with/after large meal	40%	Take after large meal - provides more gut-time for vitamin D evening meal or largest meal Note: avoid late in the evening
Common	Magnesium - low (Gut needs Mg to absorb Vit. D)	30%	Many reasons - which include low stomach acid and antacids
Common	Smoking	30%	Smoking reduces vitamin D - many studies -9 ng reduction
Common	mono-unsat fat ratio -low	20%	Need higher ratio of mono to poly fat ratio
Common	Cola - soft drinks	20%	Cola removes Calcium, Vit D consumed in restoring Calcium
Common	Oil-based Vitamin D	20%	Oil-based Vitamin D helped the least Some olive oils decrease absorption by 25 % Bio-Tech uses a water-soluble form of Vitamin D
Common	Vitamin K2 -low	10%	Overview Vitamin K and Vitamin D perhaps 100 microgram/ 1000 IU of vitamin D
Common	Boron - low	15%	Boron increases vitamin D in the blood claims 6 mg ==> 24%   -Boron is also known to build bone - perhaps by increasing vitamin D
Common	Cholesterol - reduced in diet	N.A.	Cholesterol is needed to make Vitamin D from the sun Low Cholesterol DOES NOT appear to affect vitamin D supplementation
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Sometimes	Extremely Vit D deficient	200%	Low dose can result in ZERO increase if very deficient When body is very deficient all vit. D is immediately consumed Note: sometimes extreme deficiency is due to genes.
Sometimes	Health - low	200%	Unhealthy body consumes a lot of vitamin D - see extremely deficient (Examples: MS, HIV, some cancers, Diabetes, Depression. .
Sometimes	Anemia	40%	Liver is needed to process vitamin D Sometimes need to add Iron as well as vitamin D
Sometimes	Fatty Liver	40%	Half of seniors have fatty liver, vitamin C reduces inflammation, Calcidiol or Calcitrol might be taken instead of Vitamin
Sometimes	Drugs which consume or block Vit D	50%	Taking drugs such as Statins, Antiseizure, Prednisone, AIDS drugs, Orlistat, Questran, Dilatin, Phenobarbital, Rifampin, Methamphetamine..
Sometimes	Genes	50%	Genes need to be functioning properly to process vitamin D Twin studies   Genetics    VDBP    CYP2R1  also kidney Note: sometimes cells do not get Vitamin D even though tests are OK    see below on this page
Sometimes	Taking D2 vs D3	30%	Sometimes D2 will actually DECREASE the level of D3
Sometimes	Too much UVA vs UVB	20%	UVA appears to actually DECREASE vitamin D levels Avoid getting a lot of sun thru windows or very early/late in the day
Sometimes	Winter birth	11%	Winter birth, 11 % more likely to be vitamin D deficient as an adult
Sometimes	Oral contraceptives INCREASE response	-20%	Oral Contraceptives INCREASES vitamin D levels Perhaps due to less blood loss/anemia
Sometimes	Test results inaccurate	+20% -20%	Overview  Graph of tests from 1000 labs Vitamin D differences of 5 ng are meaningless - Aug 2015
Sometimes	Gut - poor	100%	Bio-Mulsion form of vitamin D was designed for poor guts, etc
Sometimes	Probiotic + -	+20% -30%	1/3: 30% increased D bioavailability; 1/3: 20% decreases
Sometimes	DDT, pesticides	20%	Pesticides - 2016
Sometimes	Plastics (phthalates and BPA)	10%	2016
Sometimes	Vitamin A - excessive	30%	Attenuates responses for > 10,000 IU vit D: from cod liver oil or Accutane Many children in developing countries get excess Vit A doses every 6 months
Sometimes	Roundup/glyphosate	? %	Gut bacteria and liver
Sometimes	Stress	? %	Cortisol consumes Cholesterol needed to make Vitamin D
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Rare	Gallbladder removed 600,000/year in US	100%	Gallbladder essential to absorb vitamins dissolved in fats Consider other forms of Vitamin D: Biomulsion, water soluble, .
Rare	Bariatric Surgery which bypasses the small intstine	> 200%?	Vitamin D is normally adsorbed only in the small intestine will need to get alternate source of Vitamin D
Rare	Pancreatic Insufficiency	??	Fat soluble vitamins (A, D, E, K) are not absorbed as well
Rare	Liver problems	50%	Use Calcidiol or Calcitrol forms of vitamin D instead
Rare	Burned skin	70%	Burn - uncertain response to supplementation
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Sun/UV	Skin - Dark	250%	vitamin D produced varies with darkness of skin: White = 0%, Black = 250%
Sun/UV	Skin - Elderly	100%	varies with age: teenager = 0%, 60 years = 100% this due to thin skin or low cholesterol in skin
Sun/UV	Skin - Sunburned	30%	varies with % of skin which is burned Burns and bone loss    75% less
- - - - -	Reduction in Vitamin D actually getting to cells - downstream from Vitamin D Testing
Test invisible	Genes		Genes, problems which often run in families Vitamin D Receptor 341 items as of Dec 2019 Vitamin D Binding Protein 126 items as of Dec 2019 CYP27B1 25 items as od Dec 2019
Test invisible	Cells		Low Magnesium
Test invisible	Cells		Low Omega-3
Test invisible	Kidney		Poor Kidney

Note:

• Any study will rarely consider even 4 of the above factors
• Factors are sometimes additive: example, 50% + 50% = 100% = 2X as much Vitamin D is needed

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Items in both categories Genetics and Predict Vitamin D

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• Increased Vitamin D response if take cofactors, etc
• Vitamin D Nutrigenomics - High, Medium, and Low Responders - March 2019
• Response to Vitamin D - Grassroots
  • following chart shows the huge variation between individuals
  •