Quote from Orion on February 21, 2019, 6:32 am

Quote from Guest on February 20, 2019, 2:10 pm

The JP comment about using the flea control medicine... that doesn't sound like something Dr. Smith would ever recommend anyone to take even once. Has he ever even recommended any pharmaceutical to anyone? He's a naturopath. You can't take everything so seriously, I've seen reviews of businesses that were flat out revenge reviews, but the business is actually a good business, they just had it out for someone working there. Apartments tend to get horrible reviews when someone feels miffed. Happens to doctor's offices as well. I personally refuse to pay anyone to help me with nutrition, and if any practitioner whether they are a doctor or not recommended a flea medicine I'd be running for the hills. Sounds like he miffed someone and they are seeking revenge.

I was recommended the same flea med, Lufenuron, this was in 2016, I suspect he probably doesn't recommend any more. At the time is was his go to gut fix, for candida, or any type of overgrowth.  I did not take it, thought it was probably not a good idea.

Quote from John on March 17, 2019, 1:06 pm

Resistant starch may be more of a problem for people who aren't regular and stays in there gut longer.  In the large intestine black mold is said to digest what the body cannot(some prtoein I forget the name), which is a problem for mold illness according to Dr. Shoemaker.   For people that are regular daily it may be less of a problem.  I'm lucky if I can go once every 2 days.

I think combining the strategies from Dr. Shoemaker (mold detox), Andy Cutler (mercury detox), Vitamin A detox, with EMF avoidance would be a great strategy.   These are what I take into consideration now,  but it's difficult to put a good strategy together when my health and mind are already compromised.  So far its avoid mold, mercury, emf and vitamin A.  Heal gut. Take vitamin C. I'm just putting all together now. Hopefully I will see some results soon.  The one thing remains constant, was living in a high ELF- magnetic field apt. I looke forward to sleeping somewhere lowest of EMF.

Quote from rockarolla on February 7, 2021, 12:12 pm

I collected a lot of info on SCFA, mostly negative.

Note: it is mainly related to those with chronic infections like lyme, EBV etc. My personal opinion is that SCFA(from fiber) slows down innate immune system, similar to what "vitamins" A D C do and one of the many reasons vegetarians relapse so badly on the long run (in addition to chronic [animal] proteins deficiency).

Short-chain fatty acids produced by anaerobic bacteria inhibit phagocytosis by human lung phagocytes
The effect of short-chain fatty acids on the phagocytic activity of human alveolar macrophages and neutrophils was investigated. These acids, butyric, propionic, and succinic, are produced by anaerobic bacteria. The results indicate that phagocytosis of Staphylococcus aureus by human lung phagocytes is strongly inhibited by the end products of anaerobic catabolism and support the hypothesis that the antiphagocytic activity present in the supernatants of anaerobic cultures may be dependent on the presence of short-chain fatty acids.

All of the short-chain fatty acids tested induced an inhibition of phagocytosis both in absolute numbers of ingested bacteria and in rates of engulfment, which were already significant at 15 min (P < .001;figure IA right).

In the presence of short-chain fatty acids (15:1 bacteria-to PMNL ratio), a proportional decrease in the mean number of ingested bacteria (from 8 ± 0.9 to 4.1 ± 1.4) and of the metabolic activation (from 42.0 ± 2.5 fmol 02/PMNL to 27.1 ± 1.9 fmol 02/PMNL) was observed.

O2 consumption per ingested bacteria in the presence of short-chain fatty acids was not significantly different from a matched control with the same number of phagocytosed bacteria (6.58 ± 0.47 fmol OiPMNLIbacterium with short-chain fatty acids and 6.50 ± 0.52 fmol 02/PMNLIbacterium in the control). These data indicate that short-chain fatty acids did not inhibit PMNL metabolic activation and that the decreased heat effect could be accounted for by the inhibition of the phagocytosis.

Short-chain fatty acid impairment of S. aureus phagocytosis by alveolar macrophages, besides representing a good experimental model in vitro, acquires particular significance in terms of pathogenesis of mixed anaerobic lung infections, from which S. aureusis frequently retrieved [1]. The induced suppression of alveolar macrophage defense could account for the infection by S. aureus, which is normally eliminated by the resident phagocytic population without PMNL recruitment and influx of exudate [2]. From a wider infectivologic point of view, the available evidence indicates that short-chain fatty acids are important virulence factors that inhibit host phagocytic defenses as diverse as PMNLs and macrophages and may contribute to the pathogenesis of anaerobic infections.

http://blog.pnas.org/2013/05/high-fiber-diets-affect-e-coli-infections/
A high fiber diet is good for your body in more ways than one, but it could spell trouble if you eat food that’s contaminated with pathogenic Escherichia coli bacteria. A new PNAS Early Edition paper concluded that mice on high fiber diets were more likely to die from an E. coli infection than mice on low fiber diets. Fiber, the researchers found, shifts the balance and number of bacteria in the gut, making the environment more conducive to the pathogen. The finding shouldn’t discourage people from eating lots of fiber in their diets, the authors say, but helps drive forward research on why different people have different risks for developing complications from foodborne illnesses.
...
To test whether amounts of fiber in the diet influenced either the ability of E. coli O157:H7 to thrive in the body, or the way the body interacted with the Shiga toxin, O’Brien and her colleagues turned to mice. They infected mice fed high or low fiber diets with the E. coli strain, followed their reactions, and took samples of tissue from their intestines.

“It was pretty clear to us in this study that high fiber diets led to increased morbidity and mortality in animals infected with this pathogen,” says O’Brien. The mice ingesting more fiber lost more weight and were more likely to die from the E. coli. Moreover, when the team analyzed the intestinal tissue from the mice, they discovered higher levels of the Shiga toxin receptors in the mice on high-fiber diets. More receptors mean that Shiga toxin can more effectively and quickly enter the bloodstream, O’Brien says.

The link between fiber intake and the toxin receptor came when O’Brien looked at another chemical called butyrate, which is produced by a plethora of healthy gut microbes. Fibrous diets, lead the gut bacteria make more butyrate. And butyrate, she discovered, stimulates the production of the Shiga toxin receptors.

A 2010 PNAS paper comparing the gut microbiota of children from Europe and rural Africa found that those ingesting more fiber had higher levels of butyrate, O’Brien points out, providing evidence that this link likely holds true in humans as well as mice.

In addition to the differences in butyrate and receptors, the researchers also found that the mice on high fiber diets had fewer commensal (non-pathogenic) E. coli bacteria in their guts. This could open the door for the pathogenic E. coli to more effectively colonize the gut.

Induction of the Epstein-Barr virus (EBV) cycle in latently infected cells by n-butyrate.
https://www.ncbi.nlm.nih.gov/pubmed/220786

Sodium butyrate: a chemical inducer of in vivo reactivation of herpes simplex virus type 1 in the ocular mouse model.
https://www.ncbi.nlm.nih.gov/pubmed/17360760

 

Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids.
http://europepmc.org/article/PMC/4709651
Type 2 diabetes mellitus confers a threefold increased risk for tuberculosis, but the underlying immunological mechanisms are still largely unknown. Possible mediators of this increased susceptibility are short-chain fatty acids, levels of which have been shown to be altered in individuals with diabetes. We examined the influence of physiological concentrations of butyrate on cytokine responses to Mycobacterium tuberculosis (Mtb) in human peripheral blood mononuclear cells (PBMCs). Butyrate decreased Mtb-induced proinflammatory cytokine responses, while it increased production of IL-10. This anti-inflammatory effect was independent of butyrate's well-characterised inhibition of HDAC activity and was not accompanied by changes in Toll-like receptor signalling pathways, the eicosanoid pathway, or cellular metabolism. In contrast blocking IL-10 activity reversed the effects of butyrate on Mtb-induced inflammation. Alteration of the gut microbiota, thereby increasing butyrate concentrations, can reduce insulin resistance and obesity, but further studies are needed to determine how this affects susceptibility to tuberculosis.

DM patients exhibit alterations in the immune response against Mycobacterium tuberculosis (Mtb), making them more susceptible to infection or progression towards active TB disease and less responsive to treatment [8–11]. However, the underlying biological mechanisms remain largely unknown [12, 13]. DM patients have been associated with dysregulated cytokine responses to Mtb [14–17]. Whilst proinflammatory cytokines are necessary for protection against Mtb, anti-inflammatory cytokines may counteract these effects. Possible factors that may impact the host response in patients with DM are short-chain fatty acids (SCFAs), the main metabolic products of fermentation of nondigestible dietary fibres by the gut microbiota. Numerous reports have demonstrated that DM patients present with an altered composition of their gut microbiota, which subsequently alters their SCFA levels [18–24]. SCFAs strongly modulate immune and inflammatory responses [22, 25–31], thereby influencing the host response to Mtb. SCFAs, of which butyrate (C4) is the most thoroughly studied, act on immune and endothelial cells via at least two mechanisms: activation of G-protein coupled receptors (GPCRs) and inhibition of histone deacetylase (HDAC) [32]. They affect the function of various cell types such as lymphocytes [33, 34], neutrophils [25, 31, 35], and macrophages [28, 36–38]. In light of the emerging role of the microbiota in inflammation and immunity, we hypothesized that SCFAs, and in particular butyrate, may affect the immune response and susceptibility to Mtb in type 2 DM patients.

In this study we investigated the role of physiological concentrations of SCFAs on the cytokine response against Mtb in human peripheral blood mononuclear cells (PBMCs). We subsequently examined a number of possible mechanisms via which altered concentrations of one particular SCFA, C4, might affect the host immune response to Mtb in DM patients. To this purpose, we studied the influence of physiological concentrations of C4 on HDAC activity, immune signalling pathways, the eicosanoid pathway, and cellular metabolism. To our knowledge, this is the first study reporting on the effects of physiological plasma concentrations of C4 on Mtb-induced cellular responses. Physiological plasma concentrations of C4 are in the micromolar range [39], whilst in previous studies C4 has been used in the millimolar range. Thus, this study substantially adds to our knowledge of SCFAs as possible mediators of altered immune responses to Mtb in DM patients.

Short-Chain Fatty Acids Inhibit Mtb-Induced Cytokine Responses

DM is associated with altered gut microbiota and consequently altered SCFA levels [18–22]. In line with current literature [22, 25–31], we hypothesized that SCFAs have the potential to influence the host inflammatory response against Mtb. In particular we investigated the effects of varying doses of acetate (C2), propionate (C3), and butyrate (C4) on H37Rv-induced cytokine responses, with RPMI as negative control and LPS as positive control (Figure 1). SCFAs themselves did not induce cytokine production (results not shown) but significantly affected H37Rv-induced cytokine release. C2, C3, and C4 significantly, dose-dependently decreased H37Rv-induced production of proinflammatory cytokines TNF-α, IL-1β, and IL-17, while nonsignificant effects were found for IL-6, IFN-γ, and IL-22 production. In contrast, C3 and C4 induced a significant increase in H37Rv-induced production of the anti-inflammatory cytokine IL-10. Similarly, C3 and C4 but not C2 decreased LPS-induced production of TNF-α and IL-6, while the release of IL-1β was significantly decreased in response to all three SCFAs (results not shown). LPS did not induce production of IFN-γ, IL-17, or IL-22. Moreover, all three SCFAs incurred a dose-dependent, nonsignificant decrease in LPS-induced IL-10 production (results not shown).

...

We observed a general anti-inflammatory effect of C2, C3, and C4 on Mtb-induced cytokine production. C4 induced some of the most significant and most potent changes in cytokine responses, which is in line with published results [29], although our study is the first to examine the effects of physiological concentrations of SCFAs on Mtb-induced cytokine responses in vitro. Several observations were made regarding the effect of SCFA on cytokines. Firstly, the inhibitory effect of all three SCFAs on production of TNF-α and IL-1β was comparable for Mtb and LPS stimulation. However, while C3 and C4 had a clear effect on LPS-induced IL-6 release, this was not found for Mtb. This suggests that SCFAs do not affect Mtb-induced IL-6, although IL-6 has been assigned an important role in Mtb host responses [59–62]. Secondly, C2, C3, and C4 had a much stronger inhibitory effect on T-cell derived cytokine IL-17 than on T-cell derived cytokines IFN-γ and IL-22. Because C4 also strongly decreased Th17 proliferation (Supplementary Figure 5 A), SCFAs may affect Th17 subsets more than other T-cell subsets. This may be of great relevance since Th17 cells, and IL-17 in particular, have been reported to be essential in protective immunity against Mtb [63, 64] but inversely associated with DM complications [65–67]. Lastly, the stimulatory effect of C3 and C4 on anti-inflammatory IL-10 release was Mtb-specific and was not seen with LPS stimulation. IL-10 has been delineated as an important mediator in Mtb infection: it has been reported to block bacterial killing in Mtb-infected macrophages, suppress multinucleated giant cell formation and cytokine production, and inhibit the development of protective immunity [68–74]. In contrast to TB, IL-10 may have a protective role in type 2 DM by reducing insulin resistance and obesity [75–77]. Therefore, the increase in IL-10 production we see as induced by C4 is very relevant for the course of both DM and TB disease.
...
Finally, we further examined the effect of C4(butyrate) on the anti-inflammatory cytokine IL-10. IL-10 is detrimental to TB outcome, while it may improve DM symptoms [68–77]. In line with previous studies [33, 81, 82], we report an upregulation in IL-10 production induced by C4(butyrate). Removal of all intermediary protein, including IL-10, from PBMCs stimulated with H37Rv and C4(butyrate) led to a significant increase in TNF-α transcript, thereby counteracting the decrease in TNF-α production induced by C4. Moreover, blocking IL-10 specifically fully restored IL-6 responses in PBMCs stimulated with H37Rv and C4 and partly restored TNF-α and IL-1β responses. These data suggest that the anti-inflammatory cytokine IL-10 may play a role in the inhibitory effects of C4(butyrate) on Mtb-induced inflammatory responses.

Gut microbiome contributes to impairment of immunity in pulmonary tuberculosis patients by alteration of butyrate and propionate producers
https://sfamjournals.onlinelibrary.wiley.com/doi/full/10.1111/1462-2920.14015
A prominent theme that emerged from the GM(gut microbiome) data of TB patients was the significant increase in butyrate and propionate-producing bacteria (F. prausnitzii, Roseburia, E. rectale, Butyrivibrio, Phascolarctobacterium) and their related metabolic functions (butyrate and propionate metabolism). This was intriguing since F. prausnitzii is usually associated with a healthy colon and its reduction is often linked to diseased condition (Miquel et al., 2013).

To our knowledge, only one study has emphatically challenged the protective role for F. prausnitzii in all disease conditions and observed its increase in Crohn’s disease patients (Hansen et al., 2012). In view of our results, we also believe that upsurge of SCFA producers may not be beneficial in all health conditions and more elaborate studies are required to better understand their dynamic role in diverse dysbiotic conditions such as obesity and TB.

Butyrate impacts human health via its role as an antiinflammatory agent, primarily by inhibition of nuclear factor-jB activation and interferon gamma (IFN-g) signalling (Segain et al., 2000; Canani et al., 2011). The nuclear factor-jB signalling pathway is central to body’s immune response to many pathogens and is involved in transcriptional regulation of many cytokine genes, including tumor necrosis factor-alpha (TNF-a). It is known that IFN-g and TNF-a play a critical role in the control of M. tuberculosis infection and is required for formation and maintenance of granuloma. Notably, subjects with latent TB on receiving anti-TNF therapy for treatment of rheumatoid arthritis often show increased rate of reactivation of active TB. Also, TNF neutralization during a study on macaques resulted in disseminated disease (O’Garra et al., 2013). By an independent mechanism, butyrate is also known to enhance regulatory T-cells (Treg) population in the gut (Smith et al., 2013). Although Treg limits collateral tissue damage caused by vigorous antimicrobial immune responses, it suppresses the protective proinflammatory T-cell response among TB patients via interleukin-10 (IL-10) and facilitates chronic infection. Interestingly, butyrate has been implicated as a mediator of altered immune response to M. tuberculosis in diabetes mellitus patients, which may influence susceptibility to TB (Lachmandas et al., 2016).

It is suggested that various M. tuberculosis strains may induce increased production of IL-10 as a way to evade immune evasion (Redford et al., 2011). Thus, a sharp increase in butyrate levels may have deleterious effects on host immune response to M. tuberculosis infection. This highlights the fact that while reduction in butyrate-producing bacteria might be unfavourable in gastrointestinal inflammatory disorders like inflammatory bowel disease, an upsurge can also prove detrimental to the host in response to bacterial infectious diseases.

Furthermore, another characteristic feature in TB patients, as also revealed in our results, is the low blood cholesterol levels, which may get regulated by butyrate and propionate by inhibiting intestinal cholesterol biosynthesis pathway (Arora et al., 2011; Canani et al., 2011). Clinical evidence suggests that cholesterol-rich diet accelerates recovery in TB patients (Perez-Guzman et al., 2005). In light of these observations, we must consider this hypothesis that while decrease in butyrate-producing bacteria might be harmful in metabolic disorders that accompany hypercholesterolemia (Canani et al., 2011), in the case of infectious diseases like TB, an upsurge of butyrate and propionate-producing bacteria might have grave consequences on host lipid homeostatic mechanisms.

Here, an intriguing aspect that deserves attention is the apparent paradox whereby increase in serum levels of many acute-phase proteins such as C-reactive protein is observed in TB patients (Chegou et al., 2016); but, our findings reveal gut microbiome-influenced anti-inflammatory conditions, which allow increased bacterial diversity in TB patients, including many opportunistic pathogens. Notably, retroviruses are known to employ the gut microbiome to elicit IL-10 for immune subversion and utilize it for its transmission (Kane et al., 2011). We speculate that M. tuberculosis might also utilize gut microbiome for its persistence, but further studies need to be made to explore this possibility.

 

Microbial Short Chain Fatty Acids Impair Mycobacterium Avium (MAC) Clearance by Alveolar Macrophages
https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2019.199.1_MeetingAbstracts.A4242

Alveolar macrophages play a crucial role as the first line of defense against mycobacterial disease. We have previously shown that in immunocompromised patient, short chain fatty acids (SCFAs), microbial metabolites from anaerobic fermentation, are associated with increased susceptibility to mycobacterial disease. Lower airway dysbiosis characterized by enrichment with oral anaerobes are one possible source for these SCFAs. Here, we investigate whether in alveolar macrophages no vivo, if butyrate (a C4 SCFA) impairs the macrophage ability to phagocytize and kill non-tuberculous mycobacterium (NTM). Methods: Three different macrophage cell lines were used: THP-1 macrophages, monocyte GM-C SF derived macrophages, and human bronchoalveolar lavage-obtained alveolar macrophages. Cells were cultured in RPM] with and without 2mM of butyrate for 18hrs. Cells were then exposed to Mycobacterium avium complex (MAC) at a multiplicity of infection (M01) of 10 bacilli to 1 macrophage. Intracellular load of Mycobacterium was evaluated after infection at 1 hour (reflecting phagocyte capacity), 3 days, and 6 days (reflecting intracellular mycobacterial growth) by CFU counts from cell lysate grown on 7H10 Middlebrook agar plates.

Results: Overall, results were reproducible across all three macrophage types. Butyrate exposure did not affect macrophage viability assessed by Trypan blue exclusion over a period of 7 days of ex vivo culture (data not shown). At one-hour post infection, macrophages exposed to butyrate have a median -45.1%[-60.6-31.0] reduction of intracellular mycobacterial load as compared with macrophages cultured in media alone (Figure 1 A-C).

This early infection time point demonstrated that butyrate affects macrophage ability to phagocytize NTM. In contrast, intracellular mycobacterial load was increased by 57.6%[0.6-76.7] and 67.5%[55.9-89.5] respectively, after 3 and 6 days post-infection among macrophages exposed to butyrate (Figure 1A-B). CFU ratio (itch 2mM Butyrate exposure/itch control exposure) showed consistency across all macrophage cell lines (1 hour median ratio 0.5(0.4-0.6], 3 day ratio 1.5[1.0-1.7], and 6 day ratio 1.6[1.5-1.91; Figure ID). This data indicates that SCFA exposure leads to decreased phagocytosis at 1 hour and increased intracellular growth at 3 and 6 days when compared with macrophages grown in media alone. Conclusion: Butyrate modulates macrophage ability to respond to NTM infection. These findings suggest possible mechanisms by which lung dysbiosis with enrichment of oral commensals may lead to an increased susceptibility for NTM lung disease. Bacterial byproducts and metabolites may significantly impact host-immune response to pathogens.

 

Butyric Acid in Saliva of Chronic Periodontitis Patients Induces Transcription of the EBV Lytic Switch Activator BZLF1: A Pilot Study
http://iv.iiarjournals.org/content/34/2/587.full

Background/Aim: Epstein-Barr virus (EBV) associates with human chronic periodontitis (CP) progression. We previously demonstrated that butyric acid (BA), produced by periodontopathic bacteria, induced EBV lytic switch activator BZLF1 expression. We investigated whether short chain fatty acids (SCFAs) in CP patients' saliva enabled EBV reactivation. Materials and Methods: Saliva was collected from seven CP patients and five periodontally healthy individuals. SCFAs were quantified using HPLC. BZLF1 mRNA and its pertinent protein ZEBRA were determined with Real-time PCR and western blotting. Histone H3 acetylation (AcH3) was further examined. Results: BZLF1 mRNA expression and transcriptional activity in EBV-infected Daudi cells were induced only when treated with the CP saliva. Among SCFAs, BA alone correlated significantly with the BZLF1 transcription (r=0.88; p<0.02). As expected, CP patients' saliva induced AcH3. Conclusion: BA in saliva may play a role in EBV reactivation and hence contribute to EBV-related disease progression in CP patients.

Results

Saliva of CP[chronic periodontitis] patients contains relatively high levels of SCFAs. Previous studies have reported that the periodontal pockets and dental plaques of CP[chronic periodontitis] patients contain high concentrations (mM levels) of SCFAs (24-26). However, the amounts of SCFAs have not been investigated in the saliva of Japanese CP patients. Therefore, we measured the concentrations of SCFAs in the saliva of seven CP patients and five healthy controls by HPLC. As presented in Figure 1, the saliva of CP patients contained significantly higher levels (p<0.01) of BA[butyric acid], PA[propionic acid], and AA[acetic acid]. On the other hand, the amounts of isoBA and isovaleric acid in the saliva were very low.
...
The saliva of patients with periodontitis contains EBV-infected B cells, and bleeding of the gums is often observed in these patients (7, 15-17). In addition, it was recently reported that EBV infects the oral epithelial cells of patients with periodontitis in addition to the epithelial cells of the upper aerodigestive tract (30). The extent of gingival epithelial EBV infection is correlated with the severity of CP (30). Moreover, previous reports, as well as the present study, indicated that EBV also contributes to the progression of periapical periodontitis (20, 31). These findings and previous observations suggest the potential risks of BA[butyric acid] in saliva for the progression of periodontitis and periapical periodontitis. We assume that microbial synergy by the interaction between periodontopathic bacteria and EBV leads to the following negative chain of pathological events in the oral cavity: 1) periodontopathic anaerobic bacteria, such as P. gingivalis and F. nucleatum, produce BA; 2) BA induces EBV reactivation; 3) EBV impairs local host defences, 4) which leads to increased proliferation of periodontopathic bacteria; 5) increased BA and inflammatory cytokine production by the synergistic effects of EBV and periodontopathic bacteria; and 6) periodontitis escalation.
...
Periodontitis and EBV are spreading worldwide. Although our findings suggest a relationship between the saliva of patients with periodontitis and EBV reactivation, additional basic and clinical studies with greater numbers of cases are needed. Furthermore, prevention and early treatment of periodontitis involving elimination of BA[butyric acid]-producing bacteria could effectively block further clinical progression of EBV infection.

Short chain fatty acid butyrate promotes virus infection by repressing interferon stimulated genes
https://www.biorxiv.org/content/10.1101/2020.02.04.934919v1.full

Butyrate is an abundant metabolite produced by the gut microbiota and is known to modulate multiple immune system pathways and inflammatory diseases. However, studies of its effects on virus infection of cells are limited and enigmatic. We found that butyrate increases cellular infection and virus replication in influenza virus, reovirus, and human immunodeficiency virus infections. Further exploring this phenomenon, we found that addition of butyrate to cells deficient in type I interferon (IFN) signaling did not increase susceptibility to virus infection. Accordingly, we discovered that butyrate suppressed levels of specific IFN stimulated gene (ISG) products in human and mouse cells. Butyrate did not inhibit IFN-induced phosphorylation of transcription factors STAT1 and STAT2 or their translocation to the nucleus, indicating that IFN signaling was not disrupted. Rather, our data are suggestive of a role for inhibition of histone deacetylase activity by butyrate in limiting ISG induction. Global transcript analysis revealed that butyrate increases expression of more than 800 cellular genes, but represses IFN-induced expression of 60% of ISGs. Overall, we identify a new mechanism by which butyrate promotes virus infection via repression of ISGs. Our findings also add to the growing body of evidence showing that individual ISGs respond differently to type I IFN induction depending on the cellular environment, including the presence of butyrate.
...
Butyrate is a lipid produced by intestinal bacteria that can regulate inflammation throughout the body. Here we show for the first time that butyrate influences the innate antiviral immune response mediated by type I IFNs. A majority of antiviral genes induced by type I IFNs were repressed in the presence of butyrate, resulting in increased virus infection and replication in cells. This suggests that butyrate could be broadly used as a tool to increase growth of virus stocks for research and for the generation of vaccines. Our research also indicates that metabolites produced by the gut microbiome can have complex effects on cellular physiology as demonstrated by the dampening of an inflammatory innate immune pathway by butyrate resulting in a pro-viral cellular environment.
...
Of the major gut microbial metabolic end products, short chain fatty acids are of particular interest to human health. Butyrate, a 4-carbon short chain fatty acid produced from fiber metabolism, can reach concentrations as high as 140 mM in the colon, and is also present in venous blood and peripheral tissues (1, 2). Butyrate has documented roles that are largely thought to be beneficial in inflammation (3–9), adaptive immunity (2, 10–12), and in protection against bacterial infections (13, 14). Conversely, a series of classic papers showed that butyrate increased virus protein production or virion release in infections of multiple cell types with several viruses, including Epstein-Barr virus (15), measles virus (16), Borna disease virus (17), and herpes simplex virus (18). Similarly, retrovirus titers were reported to be enhanced when butyrate was added to the media of producer cells(19), leading to the use of butyrate by many laboratories in their production of retrovirus vectors. In vivo, butyrate and dietary fiber were shown to be protective against the influenza virus pathology in mice, despite an increase in virus titer (20). In contrast, butyrate and fiber were shown to be detrimental in the inflammatory disease caused by Chikungunya virus, a distinct RNA virus (21). The precise mechanisms by which butyrate affects viruses remain poorly understood and warrant further investigation given the ubiquity and abundance of this metabolite.

Butyrate increases virus infection and replication

Given that butyrate has been reported to promote replication of several viruses, we sought to examine whether this observation held true for additional viruses relevant to human health. Given that butyrate and fiber were recently suggested to modulate inflammation during influenza virus infection (20), we first pre-treated A549 lung epithelial cells with butyrate prior to H1N1 influenza A virus infection. We observed that butyrate significantly increased susceptibility of cells to influenza virus infection as measured by percent infection via flow cytometry (Fig. 1a). We also measured infectious virus levels released in cell supernatants and found that virus titers were increased by an order of magnitude in butyrate treated cells compared to mock control cells (Fig. 1b). Since the concentration of butyrate reaches its highest level in gut tissue (1, 2), we tested whether butyrate affected susceptibility of colon cells to enteric virus infection. Indeed, we observed that reovirus infection of HT-29 colon cells and resulting virus titers were both significantly increased in the presence of butyrate (Fig. 1c and d).

Likewise, since human immunodeficiency virus 1 (HIV-1) can infect and subsequently deplete gut-resident CD4+ T cells (48–50), we also examined whether butyrate altered HIV-1 infection of cells. Like influenza virus and reovirus, we observed a significant increase in HIV-1 infection and replicative capacity in butyrate treated THP1 monocytes compared to control monocytes (Fig. 1e and f). In sum, the net effect of butyrate on infection with three divergent RNA viruses was an increase in cellular infection and replication.
...
While high levels of butyrate could potentially elevate susceptibility to virus infections in vivo, butyrate has also been extensively characterized as having beneficial anti-inflammatory effects (2, 3, 6, 71, 84), which might alleviate the tissue damage resulting from viral infection and from excessive or prolonged IFN signaling. Consistent with this idea, a recent study demonstrated that mice that were fed high fiber or butyrate-rich diets had higher viral titers when challenged with influenza A virus during the early stages of infection when compared to control mice, but experienced less tissue damage to lungs during later stages of infection (20). Taken together with our findings, this suggests that high fiber diets might confer a protective advantage by reducing inflammation caused by type I IFN or other proinflammatory cytokines at the cost of temporarily increasing the overall susceptibility to virus infections.
...
Our findings implicate a previously unknown role for butyrate in differentially regulating type I IFN induced genes. Since butyrate can increase overall virus titers in cell cultures, butyrate treatment could be employed as an inexpensive strategy to increase the yield of viral vaccines or virus stocks that are produced in cell lines (85, 86). These results also suggest that treatment with butyrate or butyrogenic bacteria, which are being increasingly considered for therapeutic purposes (74, 87), should be evaluated in terms of a beneficial balance between anti-inflammatory and pro-viral effects.

 

 

 

Quote from Ourania on February 7, 2021, 9:49 pm

Thank you very much @rockarolla for this post.

All of which I had intuitively sensed before.

From the frying pan into the fire. This is what most of us have done.

I hope you are well. Wishing you the best.

Quote from Jenny on February 8, 2021, 3:04 am

Enough but not too much?

Thanks for posting all the research @rockarolla

I’ve become less & less in favour of messing around with supplements and more & more suspicious. Greg Nigh uses butyrate supplements for his sulphur programme. I only take a supplement if I build up good evidence that I’m deficient & I research any negatives. The vA supplement debacle has taught me a good lesson. I think many nutritional therapists (U.K. name)  are way too cavalier. 

Quote from rockarolla on February 8, 2021, 8:10 am

Quote from Jenny on February 8, 2021, 3:04 am

Enough but not too much?

Thanks for posting all the research @rockarolla

I’ve become less & less in favour of messing around with supplements and more & more suspicious. Greg Nigh uses butyrate supplements for his sulphur programme. I only take a supplement if I build up good evidence that I’m deficient & I research any negatives. The vA supplement debacle has taught me a good lesson. I think many nutritional therapists (U.K. name)  are way too cavalier. 

Yes, enough but not too much. For example something like beans naturally come with polyphenols + fiber(-> SCFA) which could be both useful in moderate quantities(for gut ecology), while overdosing could bring symptoms instead(unproductive inflammation) just because for example SCFA overdose leads to EBV(or other chronic [gut/intestinal] infection) spread and corresponding symptoms increase - but now from immune system which should work extra hard to keep steadiness, "thanks" to SCFA constant overdosing, while otherwise being calm.

Quote from Jenny on February 8, 2021, 8:54 am

Food rather than supplements seems to be the way when it comes to SCFAs. Let the body regulate itself. 

@are good question about B1. I don’t know. Some people have had remarkable health improvements with high dose B1 so for them it really works. I think that vA toxicity tends to deplete B1 so maybe it would be good for many of us. I just don’t know about B vitamin supplements. I think the right dose in the right order is probably life changing but getting that right isn’t easy & getting it wrong could be detrimental. If you high dose supplement one B vitamin I think other deficiencies can show up as you could be speeding up pathways that then need more co factors further down the process. If that makes sense. There will be a genetic element to this too with some enzymes needing more support in some people. I keep changing my mind about B vitamins. Sorry not very helpful! 

 

Quote from rockarolla on February 8, 2021, 9:17 am

Question is does B1 bonus holds over time. I've heard it is used even with CFS.

Quote from lil chick on February 8, 2021, 6:48 pm

Quote from Arena on February 8, 2021, 4:13 am

We should have some sort of TLDR for retards like myself who can't seem to get the idea of all these science posts.

@jaj I agree! Are you suspicious of vitamin high dose B1 as well? 

And for me too!!!!