Alzheimer's & Bacteroides fragilis

reflections passed forward (2012)...

May 07, 2025

Alzheimer’s & B. fragilis…

Updates:

Background

B. fragilis NCTC9343/atcc25285 is associated with a vast array of dis-ease states, autoimmune disorders, such as - atherosclerosis, NIDDM, autism, asthma, NAFLD and obesity, etc.

Interest in the relation between = Alzheimer's and ETBF - simply stems from the fact that the illness overlays other infections caused by B. fragilis and, specifically, the involvement of Bft (fragilysin), LPS and capsular PSA.

Thoughts

B. fragilis CPC/PSA administration or vaccination against ETBF (Bft-1,2,3 / fragilysin / EC 3.4.24.74) may be in order as Alzheimer’s appears strongly, positively and linearly associated with B. fragilis NCTC 9343/atcc25285, Bft / fragilysin producing cells. The disease may be maternally transmitted prior to 5-7 days postpartum and prior to immunological development and mature anamnestic response (if such is even possible within the host given the organism's repertoire of adaptive and virulent/survival mechanisms).

Perhaps, Alzheimer's Disease, may be defined as a disseminated microbial toxicosis relative B. fragilis entero/exo-toxin fragilysin - and perhaps resolved (“cured”) via administration of B. fragilis PSA &/or broad vaccination against B. fragilis toxin producing cells & specific epitopes raised against EC 3.4.24.74 aka "fragilysin" (Bft-1,2,3). Possibly, subsequent cellular/tissue repair could also be enhanced, expedited through utilization of: niacin + nicotinamide and CDP-choline.

If I may be so bold, by extension - I wish to (kindly/respectfully) forward the following ideas...

Regarding earliest events, it may be possible that initial development and subsequent disease process and advancement is possibly hinged upon the involvement of disseminated B. fragilis cells and disruption of cerebral circulatory vasculature.

Example:

Disruption and restructuring of collagens (i.e. IV etc) and e-cadherin, f-actin (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC173735/pdf/640113.pdf), actin and microtubule restructuring (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC174483/pdf/645022.pdf) within the basement membrane, and diverse changes relative: apoptosis, blebbing, pyknosis (http://www.ncbi.nlm.nih.gov/pubmed/1730463 ), organelle and cellular swelling - which precedes initial inflammatory and plaque forming events, may reflect the involvement of this organism &/or it's enter/exo-toxin (fragilysin/bft1,2,3).

Alzheimer's is strikingly reminiscent of the effects of fragilysin/Bft upon intestinal epithelium, and resultant pro-inflammatory response and subsequent restructuring.

As well, the unexplained early and progressive organelle swelling observed in Alzheimer's particularly relative ER (& resultant protein mis-folding?) and mitochondria (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2517415/ ) - may be explained with reference to Bacteroides fragilis (http://en.cnki.com.cn/Article_en/CJFDTOTAL-YTYS200208014.htm).

As example, it is of note also that the deposition of collagen such as type 1 http://www.jneurosci.org/content/25/48/11165.full.pdf (etc) may serve to protect tissue from B. fragilis via protein screening and cellular adhesion (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3949742/pdf/pone.0091141.pdf).

Of particular consequence is the production of the metalloprotease fragilysin/BFT (EC 3.4.24.74) - which parallels elastase associated with AD (http://www.ncbi.nlm.nih.gov/pubmed/21551909 ).

Such may, also explain the presence of foam cells/formation often present in Alzheimer's - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994432/.

B. fragilis - is likely the main culprit responsible for the vast majority of cases of atherosclerosis and Alzheimer’s dis-ease. See reference at end of writing.

Below: some examples of the overlay

between B. fragilis (BF) in Alzheimer's (AZ)

Fragilysin & other B. fragilis cellular dynamics - may shed light on just some aspects/observations relative Alzheimer's: (Variables explained by B. fragilis)

Examples... in no particular order
AZ = Alzheimer's and BF= Bacteroides fragilis

Cholesterol

AZ: http://www2.massgeneral.org/neurology/kovacs/publications/pdf/NN_AD_cholesterol_03.pdf

BF: http://www.ncbi.nlm.nih.gov/pubmed/2995802

BF: Klurfeld, cholesterol, B. fragilis, cholesterol & Brain: See Table 2
https://www.facebook.com/media/set/?set=a.119188775119645.1073741825.100010855692364&type=1&l=ea12ef799a

But why Cholesterol & how related? B. fragilis utilizes via 7 alpha hydroxysteroid dehydrogenase

Cholesterol (= B. fragilis 7a-HSD utilization): http://www.ncbi.nlm.nih.gov/pmc/articles/PMC246073/pdf/jbacter00330-0084.pdf

CNS/Brain/cholesterol (optimal/rapid growth/support for B. fragilis)

BF: http://jmm.microbiologyresearch.org/content/journal/jmm/10.1099/00222615-19-2-195?crawler=true&mimetype=application/pdf

(Results: sentence 2, Discussion: sentence 1, See: Fig. 1, Table 1)

Stat3/TH17

AZ: http://www.ncbi.nlm.nih.gov/pubmed/19663649

BF: http://www.ncbi.nlm.nih.gov/pubmed/24704822,

BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121853/pdf/nihms604331.pdf

TH17

AZ: http://www.ncbi.nlm.nih.gov/pubmed/24124514

BF: http://www.ncbi.nlm.nih.gov/pubmed/26201900

BF: (oral PSA vaccine) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995369/pdf/nihms250004.pdf

CD4+

AZ: http://www.ncbi.nlm.nih.gov/pubmed/19494434

AZ: http://www.ncbi.nlm.nih.gov/pubmed/23534386

BF: CD4+: http://www.ncbi.nlm.nih.gov/pubmed/25540199
BF: CD4+ (polarization): http://ac.els-cdn.com/S0092867405004514/1-s2.0-S0092867405004514-main.pdf?_tid=f9658a2c-a49f-11e5-a7e3-00000aab0f02&acdnat=1450344449_987d1be588161d596858b31be0123bff

CD8+

AZ: http://www.ncbi.nlm.nih.gov/pubmed/1564514

BF: (5th paragraph) http://aem.asm.org/content/76/3/936.full.pdf

CD14

AZ: http://www.ncbi.nlm.nih.gov/pubmed/21084593

BF: http://www.ncbi.nlm.nih.gov/pubmed/9587347

NK cells

AZ: http://www.ncbi.nlm.nih.gov/pubmed/22889057

BF: http://www.ncbi.nlm.nih.gov/pubmed/24439373

PMN migration

AZ: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248665/pdf/nihms644468.pdf

BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC260586/pdf/iai00091-0195.pdf

BF: http://www.ncbi.nlm.nih.gov/pubmed/3800654

PMN/neutrophil phagocytosis

AZ: (↓phagocytosis) http://www.jimmunol.org/content/194/1_Supplement/52.26

BF: (↓phagocytosis) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC260430/

BF: http://arch.neicon.ru/xmlui/bitstream/handle/123456789/4339172/JournalofInfectiousDiseasesjinfdis_145_1_145-1-72.pdf?sequence=1

Mast/histamine

AZ: http://www.ncbi.nlm.nih.gov/pubmed/9466423

BF: http://www.ncbi.nlm.nih.gov/pubmed/12793960

Foxp3+

AZ: http://www.ncbi.nlm.nih.gov/pubmed/26284939

BF: http://www.ncbi.nlm.nih.gov/pubmed/20566854
BF: CD39/Foxp3+: http://www.ncbi.nlm.nih.gov/pubmed/26230152

CD25+

AZ: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075150/

BF: http://www.nature.com/nri/journal/v10/n8/full/nri2827.html, BF:http://link.springer.com/article/10.1023%2FB%3AJOCI.0000018062.01980.ba

CD103+

AZ: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1783235/pdf/imm0103-0146.pdf

BF: http://www.ncbi.nlm.nih.gov/pubmed/20531465

increased TNF-a

AZ: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1785182/

BF: http://www.ncbi.nlm.nih.gov/pubmed/7532627,

TGF-beta (1)

AZ: http://www.ncbi.nlm.nih.gov/pubmed/17080189

BF: http://www.ncbi.nlm.nih.gov/pubmed/10691917

TLR (2 & 4)

AZ: http://www.ncbi.nlm.nih.gov/pubmed/25106635

BF: tlr2 http://www.ncbi.nlm.nih.gov/pubmed/19528164

BF: tlr4 http://www.ncbi.nlm.nih.gov/pubmed/16113279

SMAD-3

AZ: http://www.ncbi.nlm.nih.gov/pubmed/17279001

BF: http://www.ncbi.nlm.nih.gov/pubmed/20817872 (fig. 3)

WNT/beta-catenin/c-myc:

AZ: http://www.ncbi.nlm.nih.gov/pubmed/24365184, http://www.ncbi.nlm.nih.gov/pubmed/10837922

BF:http://www.jimmunol.org/content/194/1_Supplement/210.2 http://www.ncbi.nlm.nih.gov/pubmed/12557145

il1

AZ: http://www.ncbi.nlm.nih.gov/pubmed/11754997

BF: http://www.ncbi.nlm.nih.gov/pubmed/8641762

il2/il4

AZ:il2 http://www.ncbi.nlm.nih.gov/pubmed/25148802

AZ: il4 http://www.ncbi.nlm.nih.gov/pubmed/15050302

BF: http://www.ncbi.nlm.nih.gov/pubmed/?term=12812631

il6/il8

AZ: http://www.ncbi.nlm.nih.gov/pubmed/19246914, http://www.ncbi.nlm.nih.gov/pubmed/9094983

BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC517603/pdf/1918-03.pdf

il10

AZ: https://www.avactalifesciences.com/blogs/interleukin-10-anti-inflammatory-cytokine-heart-alzheimer%E2%80%99s-disease-storm

AZ: http://www.ncbi.nlm.nih.gov/pubmed/25619654

BF: http://jid.oxfordjournals.org/content/204/3/363.full.pdf

il12

BF: IL-2, IL-12 and INF-y. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176045/pdf/0008-07.pdf)

il13

AZ: http://www.ncbi.nlm.nih.gov/pubmed/22342341

BF: http://www.ncbi.nlm.nih.gov/pubmed/20817872 (p. 4103. results...)

il17/23

AZ: http://www.ncbi.nlm.nih.gov/pubmed/25138786

BF:il17 http://www.ncbi.nlm.nih.gov/pubmed/12574364
BF: il23 http://www.ncbi.nlm.nih.gov/pubmed/22695160

CXCR4

AZ: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2565515/pdf/nihms41149.pdf

BF: p.4 http://www.jimmunol.org/content/early/2014/11/08/jimmunol.1302575.full.pdf

VEGF

AZ: http://www.nature.com/articles/srep02053

BF: http://www.ncbi.nlm.nih.gov/pubmed/15317561

Sirt1

AZ: http://www.hindawi.com/journals/ijad/2012/509529/

BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3220885/pdf/nihms331000.pdf

PDGF

AZ: http://www.ncbi.nlm.nih.gov/pubmed/8544904, http://www.jbc.org/content/278/11/9290.full.pdf

BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049113/pdf/nihms275037.pdf

IGF-1

AZ: http://www.neurologyreviews.com/index.php?id=25318&tx_ttnews%5Btt_news%5D=207284

BF: http://www.ncbi.nlm.nih.gov/pubmed/16540952

Lipoproteins

AZ: http://www.ncbi.nlm.nih.gov/pubmed/18288927

BF: http://www.ncbi.nlm.nih.gov/pubmed/?term=19922

Insulin

AD/insulin: http://www.ncbi.nlm.nih.gov/pubmed/12467491

BF: Sepsis/NIDDM/insulin: http://www.jleukbio.org/content/75/3/413.full.pdf
BF: Sepsis/NIDDM/ p. 602 http://cmr.asm.org/content/20/4/593.full.pdf
BF: B. fragilis/pancreas: http://www.ncbi.nlm.nih.gov/pubmed/3882511

COX-2

AD: http://brain.oxfordjournals.org/content/131/3/651

BF: http://www.ncbi.nlm.nih.gov/pubmed/16892182

IFN

AD: http://www.ncbi.nlm.nih.gov/pubmed/19808651

BF: http://www.ncbi.nlm.nih.gov/pubmed/2434431,

BF: http://www.jimmunol.org/content/185/7/4101.full.pdf

TK/MAPK

AD: http://www.ncbi.nlm.nih.gov/pubmed/12566928

BF: http://www.ncbi.nlm.nih.gov/pubmed/16114110

CO2

AZ: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776495/pdf/nihms490459.pdf

BF: http://www.ncbi.nlm.nih.gov/pubmed/6414431

AL3+ (likely accumulated because inhibits fragilysin and limits B. fragilis cells)

AZ: http://www.ncbi.nlm.nih.gov/pubmed/21157018

BF: http://link.springer.com/article/10.1023/A%3A1003782209607#page-1

BF: (Bft ~ elastin/MMP inhibition) http://www.ncbi.nlm.nih.gov/pubmed/11733347

NO/iNOS/eNOS (flux due to zwitterionic PSA clearance)

AZ: http://www.ncbi.nlm.nih.gov/pubmed/20698819

BF: p.4 "ZPS are..." http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243960/pdf/nihms327113.pdf

Depolarization/membrane potential/ electrochemical gradient

AZ: http://www.ncbi.nlm.nih.gov/pubmed/12054502

BF: http://www.nature.com/ncomms/journal/v4/n2/full/ncomms2478.html

NFkB

AZ: http://www.ncbi.nlm.nih.gov/pubmed/9775392

BF: http://www.jimmunol.org/content/187/4/1931.full.pdf

IAP (p53/waf1...)

AZ: IAP http://www.ncbi.nlm.nih.gov/pubmed/20698819

AZ: p53 http://www.ncbi.nlm.nih.gov/pubmed/19895660

BF: http://www.ncbi.nlm.nih.gov/pubmed/18624297

Fibronectin (over-regulated due to Bft cleavage)

AZ: http://www.ncbi.nlm.nih.gov/pubmed/19864907

BF: http://www.ncbi.nlm.nih.gov/pubmed/7532044

MCP/MIP1a

AZ: http://www.ncbi.nlm.nih.gov/pubmed/16307829

BF: http://www.koreamed.org/SearchBasic.php?RID=1079JKSM/1997.32.2.201&DT=1

ICAM

AZ: http://www.ncbi.nlm.nih.gov/pubmed/1685745

BF: http://www.ncbi.nlm.nih.gov/pubmed/21724992

HLA-DR

AZ: http://www.ncbi.nlm.nih.gov/pubmed/25651370

BF: http://www.ncbi.nlm.nih.gov/pubmed/26230152

Blood type ("O" - limited protection at best, still...why the connection to AB"O" ?)

AZ: http://www.ncbi.nlm.nih.gov/pubmed/25681990

BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934257/

BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2129754/ (tbl.1,2,3)

BF: http://www.ncbi.nlm.nih.gov/pubmed/?term=6185437

BF: ultimately cannot hydrolyse http://www.ncbi.nlm.nih.gov/pubmed/?term=3117549

ACE - An ACE-Succinate connection...

AZ: http://www.ncbi.nlm.nih.gov/pubmed/10681079

Succinate: renin-ACE: Fig.1 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720812/pdf/gfn377.pdf
BF: Succinate http://www.ncbi.nlm.nih.gov/pmc/articles/PMC222221/pdf/jbacter00293-0096.pdf
BF: Captopril = Bft inhibitor - Captopril, Aprotinin: tbl. 2: http://www.pnas.org/content/suppl/2011/01/13/1012173108.DCSupplemental/pnas.1012173108_SI.pdf#ST2

Angiotensin-renin-aldosterone

BF: http://www.ncbi.nlm.nih.gov/pubmed/19202279 (C2E gene/renin binding protein)

BF: (fluid secretion) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC108111/pdf/ii001735.pdf

Sodium/chloride imbalances

AZ: http://www.ncbi.nlm.nih.gov/pubmed/22820549

BF: (proxy B. amylophilus - likely similar with B. fragilis)

http://www.ncbi.nlm.nih.gov/pubmed/4074073

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC251839/pdf/jbacter00351-0334.pdf

BF: http://iai.asm.org/content/63/10/3820.full.pdf (Cl-, tbl.1)

Chloride channel alterations: See (tbl. 1, lamb/rabbit, BFT vs. chloride)

AZ: http://www.ncbi.nlm.nih.gov/pubmed/15190104

BF: http://iai.asm.org/content/63/10/3820.full.pdf

Fibrinogen, Thrombin time, fibrin

AZ: http://www.ncbi.nlm.nih.gov/pubmed/25475538, http://www.ncbi.nlm.nih.gov/pubmed/22869464

BF: http://www.ncbi.nlm.nih.gov/pubmed/20466764,

BF: http://www.ncbi.nlm.nih.gov/pubmed/?term=6365029

Plasminogen (explaining fluctuations)

AZ: http://www.ncbi.nlm.nih.gov/pubmed/20709033

BF: http://www.ncbi.nlm.nih.gov/pubmed/18403231

Host Nicotinamide/NAD depletion: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC235550/pdf/jbacter00304-0216.pdf
It is curious that Alzheimer's disease may, in many aspects, also reflect a low

NAD/high proton state http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2617713/pdf/nihms-77725.pdf

(likely bacterial fumarate reductase pathway influence - producing H+ and utilizing host NAD).
Nicotinamide, besides repleting NAD+ levels may also serve as an inhibitor for BFT/fragilysin.

Niacin:

https://pmc.ncbi.nlm.nih.gov/articles/PMC1739176/

Niacin (lowers HMG-CoA reductase activity = low cholesterol = low BFT binding)

https://pmc.ncbi.nlm.nih.gov/articles/PMC1594844/pdf/0060-06.pdf

HSP 70

AZ: http://www.ncbi.nlm.nih.gov/pubmed/21403392

BF: http://www.ncbi.nlm.nih.gov/pubmed/26467144

HSP 90

AZ: http://www.ncbi.nlm.nih.gov/pubmed/25069659

BF: http://www.ncbi.nlm.nih.gov/pubmed/?term=19220840

CRP

AZ: http://www.ncbi.nlm.nih.gov/pubmed/23978419

BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258740/pdf/AMS-7-3-501.pdf
BF: p.794,795 http://jem.rupress.org/content/165/3/777.full.pdf

Gamma H2a

AZ: http://www.ncbi.nlm.nih.gov/pubmed/19424844

BF: http://www.ncbi.nlm.nih.gov/pubmed/?term=21876161

Beta defensin

AZ: http://www.hindawi.com/journals/tswj/2012/905785/

BF: http://www.ncbi.nlm.nih.gov/pubmed/20231411

Glucosamine

AZ: http://www.ncbi.nlm.nih.gov/pubmed/18201954

BF: http://www.ncbi.nlm.nih.gov/pubmed/3721582,
BF: tbl. 2 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1152152/pdf/biochemj00347-0205.pdf
(by extension... http://www.ncbi.nlm.nih.gov/pubmed/17007432)

COX2/PGE2

AZ: http://www.ncbi.nlm.nih.gov/pubmed/25485684

BF: http://www.ncbi.nlm.nih.gov/pubmed/16892182

ROS

AZ: http://www.ncbi.nlm.nih.gov/pubmed/21130159

BF: http://www.ncbi.nlm.nih.gov/pubmed/22075026

ENZYMES

Alkaline Phosphatase / Phosphatase

AZ: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110385/pdf/ijmeg0002-0114.pdf

BF: http://www.ncbi.nlm.nih.gov/pubmed/9468250

BF: http://ijs.microbiologyresearch.org/content/journal/ijsem/10.1099/00207713-35-3-327?crawler=true&mimetype=application/pdf

BF: http://biocyc.org/gene?orgid=BFRA272559&id=GKF0-411-MONOMER

Gamma glutamyl transferase

AZ: http://www.ncbi.nlm.nih.gov/pubmed/18416873

BF: http://www.ncbi.nlm.nih.gov/pubmed/9468250

HORMONES

Cortisol (glucocorticoid hypothesis)

AZ: http://www.ncbi.nlm.nih.gov/pubmed/17430248

BF: http://www.ncbi.nlm.nih.gov/pubmed/3514841

BF: http://aem.asm.org/content/30/1/82.full.pdf (tbl. 6)

BF: *http://www.ncbi.nlm.nih.gov/pmc/articles/PMC246073/pdf/jbacter00330-0084.pdf

Estrogen (17 beta estradiol)

BF: http://www.ncbi.nlm.nih.gov/pubmed/7392610

BF: (by proxy) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC351023/pdf/iai00153-0274.pdf

BF: * http://www.ncbi.nlm.nih.gov/pmc/articles/PMC246073/pdf/jbacter00330-0084.pdf

Progesterone

AZ: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146013/

BF: (p.261) http://iai.asm.org/content/35/1/256.full.pdf

BF: http://www.ncbi.nlm.nih.gov/pubmed/6991820

BF: (tbl. 2) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC351023/pdf/iai00153-0274.pdf

BF: * http://www.ncbi.nlm.nih.gov/pmc/articles/PMC246073/pdf/jbacter00330-0084.pdf

NEUROTRANSMITTERS

Dopamine (low due to sodium: neurotransmitter symporter uptake)

AZ: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC488258/pdf/jnnpsyc00520-0095.pdf

BF: (proxy BF ych46) http://www.uniprot.org/uniprot/Q64Z78

BF: (proxy BF ych46) http://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0005328#term=children

BF: (proxy BF ych46) http://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0005328#term=stats

Oxytocin

AZ: http://www.ncbi.nlm.nih.gov/pubmed/3587615

BF: http://www.ncbi.nlm.nih.gov/pubmed/12966884

Vasopressin

AZ: http://www.ncbi.nlm.nih.gov/pubmed/3813496

BF: (by proxy B. ruminicola) http://www.ncbi.nlm.nih.gov/pubmed/3813496

PROTEASES

Cathepsin S

AZ: http://www.ncbi.nlm.nih.gov/pubmed/7717452

BF: http://www.ncbi.nlm.nih.gov/pubmed/10865188

MMP(s) - i.e. MMP2, MMP9

AZ: http://www.ncbi.nlm.nih.gov/pubmed/21694463

BF: http://www.ncbi.nlm.nih.gov/pubmed/15677902, http://www.ncbi.nlm.nih.gov/pubmed/11833696
BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918133/

TIMP(2)

AZ: http://www.ncbi.nlm.nih.gov/pubmed/12614934

BF: http://www.jbc.org/content/288/48/34956

Alpha 1 proteinase inhibitor

AZ: http://www.ncbi.nlm.nih.gov/pubmed/1623174

BF: http://www.brenda-enzymes.org/literature.php?e=3.4.24.74&r=668836

alpha 2 macroglobulin

AZ: http://www.ncbi.nlm.nih.gov/pubmed/10959035

BF: tbl. 2 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC172975/pdf/630175.pdf
BF: (See inhibitors) http://www.brenda-enzymes.org/enzyme.php?ecno=3.4.24.74

Micro-RNAs

microRNAs: http://www.ijbs.com/v08p0171.htm

mir-29: (fig. 4) http://dmm.biologists.org/content/dmm/8/1/1.full.pdf

Homocysteine

AZ: http://www.ncbi.nlm.nih.gov/pubmed/12849121

BF: Homocysteine via B. fragilis Homocysteine thiolactonase/(aka BH): http://blast.ncbi.nlm.nih.gov/Blast.cgi

Folate (homocysteine) and MMP inhibitor link

AZ: http://ajcn.nutrition.org/content/82/3/636.abstract

MMP: http://www.ncbi.nlm.nih.gov/pubmed/21421131

BF: http://www.ncbi.nlm.nih.gov/pubmed/7806355

Bleomycin Hydrolase

AZ: http://www.ncbi.nlm.nih.gov/pubmed/10822352

BF: http://www.ncbi.nlm.nih.gov/protein/CAH07761.1

CD13/Aminopeptidase N

AZ: http://www.ncbi.nlm.nih.gov/pubmed/12935612

BF: http://www.uniprot.org/uniprot/A0A0K6BQX8

Chloride channel alterations: See (tbl. 1, lamb/rabbit, BFT vs. chloride)

AZ: http://www.ncbi.nlm.nih.gov/pubmed/15190104

BF: http://iai.asm.org/content/63/10/3820.full.pdf

Polyamine/spermine/dine:

AZ: http://www.ncbi.nlm.nih.gov/pubmed/8545054

BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174648/pdf/pnas.201010203.pdf

Complement c3

AZ: http://www.jneurosci.org/content/28/25/6333.full.pdf

BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033309/pdf/pnas.1012173108.pdf

IgA

AZ: http://link.springer.com/article/10.1007%2FBF02515005

BF: http://www.ncbi.nlm.nih.gov/pubmed/19202287

Inclusion bodies:

AZ: http://www.hindawi.com/journals/crim/2013/536231/

BF: http://www.ncbi.nlm.nih.gov/pubmed/8940763

Gamma-secretase

AZ: http://www.ncbi.nlm.nih.gov/pubmed/18625450

BF: http://www.ncbi.nlm.nih.gov/pubmed/17504810

Collagen IV

AZ: http://www.ncbi.nlm.nih.gov/pubmed/8821769

BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC172975/pdf/630175.pdf (fig. 3)

Fibrinogen

AZ: http://www.ncbi.nlm.nih.gov/pubmed/22869464, http://www.ncbi.nlm.nih.gov/pubmed/20547128

BF: http://www.pnas.org/content/108/5/1856.full.pdf (p. 1857, Proteolytic...)

BF: (Table S1, p. 7 of 8) http://www.pnas.org/content/suppl/2011/01/13/1012173108.DCSupplemental/pnas.1012173108_SI.pdf#SF1

Laminin (gamma 1 laminin, laminin-1)

AZ: (Lam-1) http://www.ncbi.nlm.nih.gov/pubmed/12111806

BF: http://www.ncbi.nlm.nih.gov/pubmed/7549160

BF: http://www.ncbi.nlm.nih.gov/pubmed/19057819

BF: (Lam-1) http://www.sciencedirect.com/science/article/pii/S0923250806002142

Paracellular barrier/Tight Junctions/ claudins /ZO-1

AZ: http://www.ncbi.nlm.nih.gov/pubmed/22237490

AZ: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887048/pdf/tisb-1-e23993.pdf

BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC175150/pdf/651431.pdf

BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC24561/pdf/pq014979.pdf

Claudin-1

AZ: CL-1 http://www.nature.com/ncomms/2015/150818/ncomms8967/pdf/ncomms8967.pdf (fig.1)

BF: CL-1 http://www2.hu-berlin.de/forschung/fdb/english/PJ/PJ1999980455.html

AZ: http://www.ncbi.nlm.nih.gov/pubmed/20707633

BF: http://jac.oxfordjournals.org/content/44/5/629.full.pdf

BF: http://www.ncbi.nlm.nih.gov/pubmed/9536953

*Perhaps, a simple idea may be the utility of compounds which raise colonic pH both proximally, distally - as enterohepatic pathway and colonic dissemination of B. fragilis (non/viable cells, outer membrane vesicles, endotoxin and fragilysin) possibly staging area.

Mitochondria relation

AZ: http://www.ncbi.nlm.nih.gov/pubmed/20442494

BF: http://www.ncbi.nlm.nih.gov/pubmed/11880608

BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC123612/

Mitochondrial/Organelle swelling

AZ: http://www.hindawi.com/journals/omcl/2014/780179/

BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC257631/pdf/iai00026-0013.pdf

BF: http://en.cnki.com.cn/Article_en/CJFDTOTAL-YTYS200208014.htm

Calcium influx (cellular)

AZ: http://www.ncbi.nlm.nih.gov/pubmed/20332425

BF: http://www.ncbi.nlm.nih.gov/pubmed/9110411

Serum calcium

AZ: http://www.sciencedirect.com/science/article/pii/0191886987900134

BF: http://www.scopemed.org/fulltextpdf.php?mno=30785

Nuclear Vitamin D receptor:

AZ: http://www.ncbi.nlm.nih.gov/pubmed/22306846

BF: http://www.ncbi.nlm.nih.gov/pubmed/25080448

Ammonia

AZ: http://www.ncbi.nlm.nih.gov/pubmed/12020619

BF: http://www.ncbi.nlm.nih.gov/pubmed/4853401

Polymicrobial - Fungi

AZ: http://www.ncbi.nlm.nih.gov/pubmed/25125470

But some examples...

Beneficial agents (other) - quick examples...

B. fragilis vaccine>B. fragilis PSA>fecal transplant or boiled/denatured/filtered oral, mucosal application

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995369/pdf/nihms250004.pdf

Possibly some efficacy...

http://www.ncbi.nlm.nih.gov/pubmed/11035726

Fumarate reductase inhibitors: Sesquiterpenes, fumaric acid esters as FRP antagonists

I.e. Berberine alkaloid (similar structure to rotenone)

AZ: http://www.ncbi.nlm.nih.gov/pubmed/22459600

BF: fig1 p927 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC235550/pdf/jbacter00304-0216.pdf

Acetyl-cysteine (NAC) - replenishes host but of low utility by B. fragilis

AZ: http://www.ncbi.nlm.nih.gov/pubmed/11673605

BF: http://www.ncbi.nlm.nih.gov/pubmed/4853401 (h2S, or cysteine)

BF: http://www.ncbi.nlm.nih.gov/pubmed/6880239

Activated charcoal (+ low dose potassium iodide)

AZ: http://www.ncbi.nlm.nih.gov/pubmed/15064035

BF: (likely ↓Bft + ↓Bacteroides load) http://www.ncbi.nlm.nih.gov/pubmed/21245127

Alpha lipoic acid (ala), diallyl disulfide (Bft zinc motif sequesterants/binding agents)
http://www.ncbi.nlm.nih.gov/pubmed/17982894, http://www.ncbi.nlm.nih.gov/pubmed/16842945

Chitosan

AZ: http://www.sciencedirect.com/science/article/pii/S0304394002000666

BF: http://www.ncbi.nlm.nih.gov/pubmed/17007432

EDTA/chelators: binds fragilysin Zn motif
http://www.brenda-enzymes.org/enzyme.php?ecno=3.4.24.74

Taurine (& DMSO, MSM…)

AZ: http://www.ncbi.nlm.nih.gov/pubmed/15003996

BF: (alters G-T ratios): http://ajcn.nutrition.org/content/24/2/218.full.pdf
(Taurochenodeoxycholic acid: http://www.ncbi.nlm.nih.gov/pubmed/23811455)
MSM ~ End group of Chemical structure of SB203580, Bft inhibitor…

Rhein

AZ: http://www.ncbi.nlm.nih.gov/pubmed/23777400

BF: http://www.ncbi.nlm.nih.gov/pubmed/3669689

Influenza vaccine

AZ: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC81665/

Protein blast with neuraminidase and hyaluronidase shows much overlap - likely conferred protection of influenza vaccine against B. fragilis

Similarly, S. pneumonia (group B) protection in AD also confers "non-traditional" protection against B. fragilis likely given that both contain zwitterionic CPC/PSA is present in both.

http://www.ncbi.nlm.nih.gov/pubmed/7927768

Niacin (G protein receptor)
AZ: http://www.ncbi.nlm.nih.gov/pubmed/21248787

BF: http://www.ncbi.nlm.nih.gov/pubmed/23365268

Taurolidine, EPPS (LPS, Bft zinc motif binding etc)
B. fragilis (etc) endotoxin: http://www.ncbi.nlm.nih.gov/pubmed/11035726

Captopril, Aprotinin: tbl. 2

AZ: http://www.ncbi.nlm.nih.gov/pubmed/23959119

BF:http://www.pnas.org/content/suppl/2011/01/13/1012173108.DCSupplemental/pnas.1012173108_SI.pdf#ST2

Fragilysin inhibitors: quercetin
AZ: http://www.ncbi.nlm.nih.gov/pubmed/25666032

BF: http://www.brenda-enzymes.org/enzyme.php?ecno=3.4.24.74

Chloro/Quinolone(s) (fits BFT/fragilysin enzymatic cleft pocket very well)

BF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC188049/pdf/aac00030-0167.pdf

AZ:

https://www.google.ca/?gfe_rd=cr&ei=xeJ6VtrvNKPP8gftzq1Q&gws_rd=ssl

AZ: hepps/epps http://www.chemicalbook.com/ChemicalProductProperty_EN_CB9310937.htm

Antibiotics (Multi-antibiotic regimen): clavulanate + Pen G, tetracycline, metronidazole
Need for multi-antibiotic cocktail; p. 1856, last paragraph: ETBF can be resistant to antibiotics such as

penicillin, ampicillin, clindamycin, tetracycline, and metronidazole... http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033309/pdf/pnas.1012173108.pdf

3-methylpyridine structures: pirfenidone, rupatadine, ligustrazine, thymine
http://www.frontiersin.org/10.3389/conf.fimmu.2013.02.00431/event_abstract

http://www.ncbi.nlm.nih.gov/pubmed/22415639

Bft / “fragilysin’ specific (Brenda: EC 3.4.24.74) - please see…

https://www.brenda-enzymes.org/enzyme.php?ecno=3.4.24.74#INHIBITOR

Again, but some examples...

End

As mentioned, I have attached a (pulsed/accelerated) videos- regarding atherosclerosis as filtered through the eyes of B. fragilis (but yet the host fails to see the connection). Project/video is where/why I first observed such similarity with AD.

Video simply created in 2011 for my own musing, again starts slow but becomes very fast(can be paused) - but gives a glimpse of disease through the eyes of B. fragilis in atherosclerosis - may be similar/identical for Alzheimer's disease... the difference is merely 'geography' relative this pathogen. (CNS is a rich source of cholesterol, sphingolipids, choline & glucose)

Before closing, a curiosity... that the hallmark of Alzheimer's disease is in many regards the production and presence of amyloid beta A4 protein - but why this protein, and why is this so?

This may simply serve a protective function. It is of interest that AbA4 of 770 AA's in length, contains 17 cysteine linkages within the first 350 AA's but is perfectly absent (as I guessed upon curiosity) in the remaining >1/2 (420) of the remaining structure. I believe, though I may be incorrect, that the answer is found in C-G and C-L linkages which are cleaved via B. fragilis CD13 and fragilysin, respectively.

I tend to believe that cysteine linkages are of vital importance, given the organism's adaptive and evolutionary propensity for cysteine as a main/exclusive sulfur source (and likely represents the cleavage of glutathione in AD). The absence of such in the remaining structure may minimize hydrolytic damage - a form of protective, host preservational 'shielding'/screening/damming...

Hope such may serve value.

oliver ennis

2012

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