S-VV's desperation medicine

[JES]

So is there no place in the USA or another country to do Phage Therapy? If so, why?

I read a story about a man here who managed to get phage therapy for a bug that didn't respond to antibiotics. This was in the USA. But it seems practically impossible for anyone with "just" ME/CFS to get this sort of therapy in the USA without some special connections. Georgia and some east European countries have a long history of developing phage treatments, whereas in the west all focus on phages basically stopped when antibiotics came to market.

 

[Wishful]

Kind of hard to get phage therapy for ME when no one knows which bacteria to target, or even if a bacteria is involved.

 

[tyson oberle]

Kind of hard to get phage therapy for ME when no one knows which bacteria to target, or even if a bacteria is involved.

Wishful or anyone else in this forum, what about streptococcus? Could an overgrowth of this bacteria cause ME/CFS?

A 58-year-old patient diagnosed with fibromyalgia, irritable bowel syndrome (IBS) and chronic fatigue syndrome (CFS), non-responsive to variety of treatments over the years, suffered from significant social and occupational disabilities. The patient was interested in fecal microbiota transplantation (FMT), but given that FMT is not approved for these indications, he used an online protocol for FMT screening and preparation and self-instilled the filtrate using an enema 6 times. FMT resulted in a gradual improvement of symptoms and 9 months after the last treatment, the patient reported full recovery of symptoms, going back to work at full time employment. Improvement of symptoms was associated with major alterations of the enteric microbiota, according to next generation sequencing analysis performed before the first FMT and after the last FMT. Most prominent alterations at the genus level included a decrease in fecal Streptococcus proportion from 26.39% to 0.15% and an increase in Bifidobacterium from 0% to 5.23%. This case is added to several additional case reports that demonstrated the effectivity of FMT in these functional disorders that are lacking an otherwise good medical therapeutic intervention. We conclude that randomized controlled trials are required to ground FMT as a possible therapy for these difficult-to-treat conditions.

 

[Wishful]

Could an overgrowth of that bacteria or any other type trigger ME or make symptoms worse? I expect it's possible. Does it? You'd need a research team to answer that question. As for what causes ME/CFS, that's a question the research groups are working on, and still haven't reported finding an answer.

I expect that if you found two ME/CFS victims with high levels of bacteria 'x' and managed to reduce that population, one person might report a reduction in ME/CFS symptoms, and the other wouldn't. I think it highly unlikely that one bacteria species is going to be a factor in anything more than a very small number of ME/CFS victims. I think it's more likely that of the ones who are affected by bacteria, there will be a wide range of species involved...and it still won't be the core dysfunction of ME/CFS.

 

[S-VV]

Short update: the cold symptoms have subsided, but I still experience the quick accumulation of lactic acid upon any kind of exertion. Is it the CDR or the microbiome overproducing D-Lactate?

At any rate, today I took my first Doxy@100mg. Let's see how it goes. The plan is doxy 2/d@100mg plus Amoxicilin 3 or 4 days later unless the doxy-herx is too intense.

Time to put the microbiome CFS-model to the test

 

[S-VV]

I have been taking doxy @ 100mg 2xDay for four days. Noticeable benefits. I went from 30% to 60% functionality. The lactic acid in the muscles is greatly reduced. I have now added azithromycin 250mg 2xDay. No noticeable herx, but my gut does feel "strange", for lack of a better word.

Instead of having diarrhea, I'm actually a bit constipated.

My neck lymph nodes have shrunk quite a bit, but they sometimes hurt, usually at the same time when my armpits (more lymph) do. I imagine this is due to the increased LPS from dead bacteria.

I've added C. Butycurum to further lower lactate and allow for colonization of pH sensitive species. I've also added symbioflor-2 (E.coli) to compete with the bad cocci, mainly Streptotoccus.

 

[S-VV]

I should also mention that I've dropped all my supplements save for LDN and nimodipine. They aren't worth the $$$ and I'm saving for an O3 generator, mHBOT, rife and the Bob Beck protocol.

 

[Wishful]

Just took a look online for ozone generators, and they seem rather expensive for what's inside. I don't believe they'll help with ME, but if you do, you could build your own for probably a few dollars. All it is is a high voltage source with an electrode (just a bare wire will do) in the air. I've seen plans for them in electronic magazines; the designs are simple. Alternatively, you could use a whimshurst or van de graaff generator, or a tesla coil (also lots of hobbyist plans for those around).

 

[S-VV]

Thanks for the ideas, but considering I want to insuflate the O3 rectally, it may be better not to do it myself!

Is there a difference between Corona discharge and VdGraaf or whinshurst?

 

[Wishful]

I haven't really looked into it, but I expect that a tesla coil (HV AC) would create positive and negative ions, while HV DC would create positive or negative. I'm not sure which would be better at producing ozone.

I strongly suggest reading more about ozone from sources that aren't profiting from it. A quick check shows a lot of blatant quackery. I'm not sure how it can provide much of a benefit inside a body. Yes, it can kill nasty microbes, but it equally well destroys healthy cells. It's pure, unspecific destruction of organic matter. It will not be targeted at only bad microbes. You might as well be treating yourself with chlorine or fluorine; both probably aren't much more destructive to organic material. Based on the little I've bothered to look into it, I rate ozone therapy and not only quackery, but dangerous quackery.

 

[S-VV]

Well, even hard-core skeptics like @Hip agree that O3 could be a good idea, less because of the direct microbe killing effect, and more because of the inmune stimulating and hormetic responses it elicits.

I thank you for warning me about the possible dangers of oxidative therapy, but my experience with it (concretely using MMS) have been very helpful.

 

[S-VV]

Update: Im now in full Jarisch-Herxheimer territory. Aspirin helps a lot. Also considering using cyproheptadine. Is it lyme of microbiome die off? I don't know.

Coincidentally the die off started 36h after staring E.coli probiotic

 

[S-VV]

STUDY 1: Vagus nerve stimulation helps w/ autoimmune disorder

The Effects of Noninvasive Vagus Nerve Stimulation on Fatigue and Immune Responses in Patients With Primary Sjögren's Syndrome.
Tarn J1, Legg S1, Mitchell S1, Simon B2, Ng WF1.
Author information

Abstract
OBJECTIVES:
Primary Sjögren's syndrome (pSS) sufferers have rated chronic fatigue as the most important symptom needing improvement. Emerging data suggest that stimulation of the vagus nerve can modulate immunological responses. The gammaCore device (electroCore), developed to stimulate the cervical vagus nerve noninvasively, was used to assess the effects of vagus nerve activation on immune responses and clinical symptoms of pSS.

MATERIALS AND METHODS:
Fifteen female pSS subjects used the nVNS device twice daily a 26-day period. At baseline, blood was drawn before and after application of the gammaCore device for 90 sec over each carotid artery. The following fatigue-related outcome measures were collected at baseline, day 7 and day 28: EULAR patient reported outcome index, profile of fatigue (Pro-F), visual analogue scale of abnormal fatigue, and Epworth sleepiness scale (ESS). Whole blood samples were stimulated with 2 ng/mL lipopolysaccharide (LPS) and the supernatant levels of IFNγ, IL12-p70, TNFα, MIP-1α, IFNα, IL-10, IL-1β, IL-6, and IP-10 were measured at 24 hours. In addition, clinical hematology and flow cytometric profiles of whole blood immune cells were analyzed.

RESULTS:
Pro-F and ESS scores were significantly reduced across all three visits. LPS-stimulated production of IL-6, IL-1β, IP-10, MIP-1α, and TNFα were significantly reduced over the study period. Patterns of NK- and T-cell subsets also altered significantly over the study period. Interestingly, lymphocyte counts at baseline visit correlated to the reduction in fatigue score.

CONCLUSION:
The vagus nerve may play a role in the regulation of fatigue and immune responses in pSS and nVNS may reduce clinical symptoms of fatigue and sleepiness. However, a sham-controlled follow-up study with a larger sample size is required to confirm the findings

STUDY 2: MIcrobiome wipeout helps w/ autoimmune disorder

Oral antibiotics as a novel therapy for arthritis: evidence for a beneficial effect of intestinal Escherichia coli.
Nieuwenhuis EE1, Visser MR, Kavelaars A, Cobelens PM, Fleer A, Harmsen W, Verhoef J, Akkermans LM, Heijnen CJ.
Author information

Abstract
OBJECTIVE:
The intestinal flora is thought to play an important role in regulation of immune responses. We investigated the effects of changing the intestinal flora on the course of adjuvant-induced arthritis (AIA) and on experimental autoimmune encephalomyelitis (EAE) by the use of oral antibiotics.

METHODS:
Oral treatment with either vancomycin or vancomycin, tobramycin, and colistin was started after AIA and EAE induction. Clinical symptoms of AIA and EAE were monitored, and microbial analysis of ileal samples was performed.

RESULTS:
Oral vancomycin treatment after disease induction significantly decreased clinical symptoms of AIA. Simultaneously, increased concentrations of Escherichia coli were detected in the distal ileum of vancomycin-treated rats. Ileal concentrations of E coli were inversely related to disease scores in rats with AIA. Coadministration of colistin/tobramycin to prevent the increase in E coli abrogated the beneficial effect of vancomycin on AIA. Vancomycin treatment also reduced the clinical symptoms of EAE.

CONCLUSION:
We propose oral vancomycin as a novel therapeutic strategy in autoimmune diseases


STUDY 3: Disbiosys negatively affect vagus nerve

The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis
Bruno Bonaz,1,2,* Thomas Bazin,3,4 and Sonia Pellissier5

Abstract
The microbiota, the gut, and the brain communicate through the microbiota-gut-brain axis in a bidirectional way that involves the autonomic nervous system. The vagus nerve (VN), the principal component of the parasympathetic nervous system, is a mixed nerve composed of 80% afferent and 20% efferent fibers. The VN, because of its role in interoceptive awareness, is able to sense the microbiota metabolites through its afferents, to transfer this gut information to the central nervous system where it is integrated in the central autonomic network, and then to generate an adapted or inappropriate response. A cholinergic anti-inflammatory pathway has been described through VN's fibers, which is able to dampen peripheral inflammation and to decrease intestinal permeability, thus very probably modulating microbiota composition. Stress inhibits the VN and has deleterious effects on the gastrointestinal tract and on the microbiota, and is involved in the pathophysiology of gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) which are both characterized by a dysbiosis. A low vagal tone has been described in IBD and IBS patients thus favoring peripheral inflammation. Targeting the VN, for example through VN stimulation which has anti-inflammatory properties, would be of interest to restore homeostasis in the microbiota-gut-brain axis

 

[S-VV]

Safety and efficacy of vagus nerve stimulation in Fibromyalgia: A Phase I/II proof of concept trial

Abstract
Objective
We performed an open label Phase I/II trial to evaluate the safety and tolerability of vagus nerve stimulation (VNS) in patients with treatment-resistant fibromyalgia (FM) as well as to determine preliminary measures of efficacy in these patients.

Methods
Of 14 patients implanted with the VNS stimulator, 12 completed the initial 3 month study of VNS; 11 returned for follow-up visits 5, 8 and 11 months after start of stimulation. Therapeutic efficacy was assessed with a composite measure requiring improvement in pain, overall wellness, and physical function. Loss of both pain and tenderness criteria for the diagnosis of FM was added as a secondary outcome measure because of results found at the end of 3 months of stimulation.

Results
Side effects were similar to those reported in patients treated with VNS for epilepsy or depression and, in addition, dry mouth and fatigue were reported. Two patients did not tolerate stimulation. At 3 months, five participants had attained efficacy criteria; of these, two no longer met widespread pain or tenderness criteria for the diagnosis of FM. The therapeutic effect seemed to increase over time in that additional participants attained both criteria at 11 months.

Conclusions
Side effects and tolerability were similar to those found in disorders currently treated with VNS. Preliminary outcome measures suggested that VNS may be a useful adjunct treatment for FM patients resistant to conventional therapeutic management but further research is required to better understand its actual role in the treatment of FM


A health rising article about the study:

Vagus nerve stimulation is one of the most promising chronic pain interventions under development today. An earlier blog on Health Rising featured an astonishing story of a woman whose very severe fibromyalgia was largely ameliorated by a vagus nerve stimulator implant.

She was part of a small 2011 study which suggested that VNS may be very effective in fibromyalgia. The study was small but the success rate was high. Dr. Natelson, a neurologist who’s been treating and researching FM and ME/CFS for decades said:

“The results blew me away. I have never seen an effect as powerful as this.”

Many of the participants in that study no longer met the criteria for FM after it: that’s a criteria for success that few FM studies are willing to even contemplate using

 

[S-VV]

More on the vagus nerve + micro biome:

Vagal pathways for microbiome-brain-gut axis communication.
Forsythe P1, Bienenstock J, Kunze WA.
Author information

Abstract
There is now strong evidence from animal studies that gut microorganism can activate the vagus nerve and that such activation plays a critical role in mediating effects on the brain and behaviour. The vagus appears to differentiate between non-pathogenic and potentially pathogenic bacteria even in the absence of overt inflammation and vagal pathways mediate signals that can induce both anxiogenic and anxiolytic effects, depending on the nature of the stimulus. Certain vagal signals from the gut can instigate an anti-inflammatory reflex with afferent signals to the brain activating an efferent response, releasing mediators including acetylcholine that, through an interaction with immune cells, attenuates inflammation. This immunomodulatory role of the vagus nerve may also have consequences for modulation of brain function and mood.What is currently lacking are relevant data on the electrophysiology of the system. Certainly, important advances in our understanding of the gut-brain and microbiome- gut-brain axis will come from studies of how distinct microbial and nutritional stimuli activate the vagus and the nature of the signals transmitted to the brain that lead to differential changes in the neurochemistry of the brain and behaviour.Understanding the induction and transmission of signals in the vagus nerve may have important implications for the development of microbial-or nutrition based therapeutic strategies for mood disorders

 

[S-VV]

The microbiome: A key regulator of stress and neuroinflammation

 

[S-VV]

OK, enough about the vagus. Time to center on how the host regulates its micro biome composition:

Host adaptive immunity alters gut microbiota.
Zhang H1, Sparks JB2, Karyala SV3, Settlage R3, Luo XM4.
Author information

Abstract
It has long been recognized that the mammalian gut microbiota has a role in the development and activation of the host immune system. Much less is known on how host immunity regulates the gut microbiota. Here we investigated the role of adaptive immunity on the mouse distal gut microbial composition by sequencing 16 S rRNA genes from microbiota of immunodeficient Rag1(-/-) mice, versus wild-type mice, under the same housing environment. To detect possible interactions among immunological status, age and variability from anatomical sites, we analyzed samples from the cecum, colon, colonic mucus and feces before and after weaning. High-throughput sequencing showed that Firmicutes, Bacteroidetes and Verrucomicrobia dominated mouse gut bacterial communities. Rag1(-) mice had a distinct microbiota that was phylogenetically different from wild-type mice. In particular, the bacterium Akkermansia muciniphila was highly enriched in Rag1(-/-) mice compared with the wild type. This enrichment was suppressed when Rag1(-/-) mice received bone marrows from wild-type mice. The microbial community diversity increased with age, albeit the magnitude depended on Rag1 status. In addition, Rag1(-/-) mice had a higher gain in microbiota richness and evenness with increase in age compared with wild-type mice, possibly due to the lack of pressure from the adaptive immune system. Our results suggest that adaptive immunity has a pervasive role in regulating gut microbiota's composition and diversity.

Whooops!! I thought "microbiome diversity" was good for us. Well, it turns out immunodeficient mice have more diversity because our inmune system exerts a negative control on the microbiome, mainly through sIgA:

Policing of gut microbiota by the adaptive immune system

• Laurent Dollé,
• Hao Q. Tran,
• Lucie Etienne-Mesmin and
• Benoit Chassaing

Abstract
The intestinal microbiota is a large and diverse microbial community that inhabits the intestine, containing about 100 trillion bacteria of 500-1000 distinct species that, collectively, provide benefits to the host. The human gut microbiota composition is determined by a myriad of factors, among them genetic and environmental, including diet and medication. The microbiota contributes to nutrient absorption and maturation of the immune system. As reciprocity, the host immune system plays a central role in shaping the composition and localization of the intestinal microbiota. Secretory immunoglobulins A (sIgAs), component of the adaptive immune system, are important player in the protection of epithelium, and are known to have an important impact on the regulation of microbiota composition. A recent study published in Immunity by Fransen and colleagues aimed to mechanistically decipher the interrelationship between sIgA and microbiota diversity/composition. This commentary will discuss these important new findings, as well as how future therapies can ultimately benefit from such discovery

 

[S-VV]

In addition to sIgA, the body also controls micro biome size and population by depriving it of Nitrogen:

Microbial nitrogen limitation in the mammalian large intestine

Abstract
Resource limitation is a fundamental factor governing the composition and function of ecological communities. However, the role of resource supply in structuring the intestinal microbiome has not been established and represents a challenge for mammals that rely on microbial symbionts for digestion: too little supply might starve the microbiome while too much might starve the host. We present evidence that microbiota occupy a habitat that is limited in total nitrogen supply within the large intestines of 30 mammal species. Lowering dietary protein levels in mice reduced their faecal concentrations of bacteria. A gradient of stoichiometry along the length of the gut was consistent with the hypothesis that intestinal nitrogen limitation results from host absorption of dietary nutrients. Nitrogen availability is also likely to be shaped by host–microbe interactions: levels of host-secreted nitrogen were altered in germ-free mice and when bacterial loads were reduced via experimental antibiotic treatment. Single-cell spectrometry revealed that members of the phylum Bacteroidetes consumed nitrogen in the large intestine more readily than other commensal taxa did. Our findings support a model where nitrogen limitation arises from preferential host use of dietary nutrients. We speculate that this resource limitation could enable hosts to regulate microbial communities in the large intestine. Commensal microbiota may have adapted to nitrogen-limited settings, suggesting one reason why excess dietary protein has been associated with degraded gut-microbial ecosystems

 

[S-VV]

Finally, if you have dysbiosis, consuming fiber may be a very bad thing:

Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer.
Singh V1, Yeoh BS2, Chassaing B3, Xiao X4, Saha P1, Aguilera Olvera R4, Lapek JD Jr5, Zhang L6, Wang WB7, Hao S8, Flythe MD9, Gonzalez DJ5, Cani PD10, Conejo-Garcia JR11, Xiong N7, Kennett MJ7, Joe B1, Patterson AD7, Gewirtz AT12, Vijay-Kumar M13.
Author information

Abstract
Dietary soluble fibers are fermented by gut bacteria into short-chain fatty acids (SCFA), which are considered broadly health-promoting. Accordingly, consumption of such fibers ameliorates metabolic syndrome. However, incorporating soluble fiber inulin, but not insoluble fiber, into a compositionally defined diet, induced icteric hepatocellular carcinoma (HCC). Such HCC was microbiota-dependent and observed in multiple strains of dysbiotic mice but not in germ-free nor antibiotics-treated mice. Furthermore, consumption of an inulin-enriched high-fat diet induced both dysbiosis and HCC in wild-type (WT) mice. Inulin-induced HCC progressed via early onset of cholestasis, hepatocyte death, followed by neutrophilic inflammation in liver. Pharmacologic inhibition of fermentation or depletion of fermenting bacteria markedly reduced intestinal SCFA and prevented HCC. Intervening with cholestyramine to prevent reabsorption of bile acids also conferred protection against such HCC. Thus, its benefits notwithstanding, enrichment of foods with fermentable fiber should be approached with great caution as it may increase risk of HCC

 

[S-VV]

@mariovitali 's algorithms concluded that the liver plays a central role in ME/CFS. He has also talked about the gut-liver axis, and about the potential benefits UDCA can give:


Anti-inflammatory effects of ursodeoxycholic acid by lipopolysaccharide-stimulated inflammatory responses in RAW 264.7 macrophages.
Ko WK1, Lee SH2, Kim SJ1, Jo MJ1, Kumar H1, Han IB1, Sohn S1.
Author information

Abstract
PURPOSE:
The aim of this study was to investigate the anti-inflammatory effects of Ursodeoxycholic acid (UDCA) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages.

METHODS:
We induced an inflammatory process in RAW 264.7 macrophages using LPS. The anti-inflammatory effects of UDCA on LPS-stimulated RAW 264.7 macrophages were analyzed using nitric oxide (NO). Pro-inflammatory and anti-inflammatory cytokines were analyzed by quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The phosphorylations of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 in mitogen-activated protein kinase (MAPK) signaling pathways and nuclear factor kappa-light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) signaling pathways were evaluated by western blot assays.

RESULTS:
UDCA decreased the LPS-stimulated release of the inflammatory mediator NO. UDCA also decreased the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin 1-α (IL-1α), interleukin 1-β (IL-1β), and interleukin 6 (IL-6) in mRNA and protein levels. In addition, UDCA increased an anti-inflammatory cytokine interleukin 10 (IL-10) in the LPS-stimulated RAW 264.7 macrophages. UDCA inhibited the expression of inflammatory transcription factor nuclear factor kappa B (NF-κB) in LPS-stimulated RAW 264.7 macrophages. Furthermore, UDCA suppressed the phosphorylation of ERK, JNK, and p38 signals related to inflammatory pathways. In addition, the phosphorylation of IκBα, the inhibitor of NF-κB, also inhibited by UDCA.

CONCLUSION:
UDCA inhibits the pro-inflammatory responses by LPS in RAW 264.7 macrophages. UDCA also suppresses the phosphorylation by LPS on ERK, JNK, and p38 in MAPKs and NF-κB pathway. These results suggest that UDCA can serve as a useful anti-inflammatory drug