Last Updated on October 2, 2018 by Patricia Carter

SUMMARY:  This post is a followup to the post, IBD CROHN’S: SCD INCREASED MICROBIOME DIVERSITY BUT LOW RESIDUAL DIET REDUCED DIVERSITY.  It discusses the significance of the finding that SCD increased F. prausnitzii within the microbiome for Crohn’s patients eating SCD.  I’d suspect however, that similar results occur even for non-Crohn’s SCD consumers, which would be a good thing. For details of the microbiome changes due to SCD (microbial diversity increased to include 134 bacteria belonging to 32 different classes (Figure 8), the bacterial families over represented in the increase included over 20 species of the non-pathogenic clostridia family and more) read the post IBD CROHN’S: SCD INCREASED MICROBIOME DIVERSITY BUT LOW RESIDUAL DIET REDUCED DIVERSITY.  Think about the 3.5 to 5 pounds of bacteria that lives on and in us: what are they, how did they get there, and what does their mix mean for our health?  Ends up, F. prausnitzii is a major player in gut health and those having more of it fare better, at least for IBD where F. prausnitzii seems to be reduced.  In summary, F. prausnitzii protects against pathogen invasion, modulates the immune system, is an acetate consumer, and is a producer of substantial quantities of butyrate as well as high amounts of antioxidant compounds.  Some call F. prausnitzii a keystone peacekeeping microbe.  

Note:  This post has been requested, and it is long documenting much science.  The take home message for many eating whole foods, SCD, GAPS, PALEO, WAHLs Protocol… is at the bottom of the post, below the “Chicken Run” image, which you can skip to at any time and that is the foods that help F. prausnitzii bloom. 

‘Omics’:  Bacterial and  human genes together determine host metabolic profile including mRNA, protein, metabolite production and their byproducts, all of which effects health

This section is important to understand because to say “SCD increased F. prausnitzii  for Crohn’s while concomitantly Proteobacteria decreased,”  is NOT that simple.  Species have overlapping functions.  That is vital given that our environment (including diet, antibiotics and so much more) constantly challenges the microbiome community composition.  A better way of understanding “Who is in the microbiome,” is to learn “What are they doing?”

This section is taken from week 2 class, Gut Microbiome Gut Check: Exploring the Microbiome, 2014, instructors:  Dr. Katherine Amato, Dr. Luke Thompson, Dr. Janet Jansson, and Dr. Pieter Dorrestein.  A fecal sample contains much more than bacteria; it contains human cells, bacterial cells, food particles, microbial eukaryote (TMI perhaps but this is an organism with a complex cell or cells, in which the genetic material is organized into a membrane-bound nucleus or nuclei), and viruses. Viruses are two forms: one infects human cells and the other infects bacteria which are call bacteriophage.  Microbiome sequencing ‘Omics’ technologies reveal:

1. the microbes present and their genes,
2. which genes are used the most,
3. which proteins the genes are making, and
4. how is the body using the proteins.

The study of DNA is genomics.  The study of RNA is transcriptomics.  DNA is like a desktop computer holding all the files and RNA is the USB drive that transports the files.  Transcriptomics is sequencing the RNA.  This helps us to understand who is in the environment and what are they doing.  This the most accurate way to see what genes are being used in the bacteria.  Microbes that bloom use genes that allow them to perform their functions.  The different genetic function of the bacteria is activated in response to the environment which includes what food the bacteria consumes.  In transcriptomics, RNA is translated into amino acids that are strung together into proteins, and they are the workhorse of the cell.  Proteins are large molecules that perform many functions including:

1. Moving other molecules,
2. Signaling other cells. and
3. Initiating important chemical reactions.
   

   

   Source: Intro2Res International 2014, http://intro2res2014.blogspot.com/2014/10/omics-technologies.html

Proteomics goes beyond the composition of the community to understand the function.  It is not just who the microbes are, but what are they doing.  Here we learn the impact the microbes have on our body.

Researchers end up with a lot of data with the omics technologies. The challenge is to synthesize all into one cohesive story. Computational advances will help researchers to see the whole picture.  Beyond the technology though is the link between the gut and brain.  An example is the Naval funded studies looking at the impact of circadian rhythm for crewmen on submarines and tentatively, they are finding gut microbiome impact.  In summary, F. prausnitzii increase for SCD Crohn’s microbiome is significant and the clinical findings that evidence Crohn’s disease activity indices improvement and mucosal healing cuts to the chase of the omics technologies which needs yet to  catch-up to answer the science who, what and why.

“The intestinal microbiota metabolize exfoliated epithelial cells, dietary carbohydrates, and mucus, producing metabolites that affect the function of intestinal epithelial cells and influence host energy balance, immune regulation and homeostasis, and hepatic function. The impact of this bidirectional communication between the microbiota and the host is so profound that some have proposed that humans should be considered “superorganisms” composed of bacterial and human genes that, together, determine the metabolic profile of the host.” –Intestinal Microbes in Inflammatory Bowel Diseases.  

Now you understand that to say SCD increased F. prausnitzii  for Crohn’s while concomitantly Proteobacteria decreased,  is NOT that simple.

The diversity of microbial genes (microbiome) and the activity of these genes:  mRNA, protein, metabolite production and their byproducts as microbes go about their metabolic activities have an effect on health outcomes.  The resultant functional  microbiome, human and microbiota, is not addressed in this post as science profiling is not there yet for SCD.  That SCD is now found to improve  IBD disease activity indices and result in gut mucosal healing, would be indications that the functional SCD microbiome is being optimized, I would surmise. 

At this time, researchers are finding healing with SCD (disease activity indices as well as mucosal).  See:

1. Concise Summary of SCD Studies.
2. The post FOOD MANAGING IBD & AUTISM: THE STUDIES, and
3. The SCD studies noted in the Dec 2014 Advances in IBD conference presentation “Probiotics, Special Diets [SCD], and Complementary Therapies:  We Know Patients Want Them, So What Do We Tell Them?”   The links to this presentation’s PowerPoint and YouTube are in the post, CAMS [ARTEMISIA, SCD…] & INTEGRATIVE MEDICINE BENEFITS GUT HEALTH.  

These findings  which suggest the functional SCD microbiome is being optimized likely holds true for others using SCD for disease prevention or other health concerns — for example:   Small Intestinal Bacterial Overgrowth (SIBO), or arthritis, ARTHRITIS & GUT HEALTH: DIET & MICROBIOME.  I would also suspect similar is occurring for those realizing health gains using diets similar to SCD such as GAPS/ PALEO/ WAHL’s Protocol…

Sooo.. Who actually is in our gut, and why are they there?

Diet greatly determines our microbiome and while the below addresses IBD, any disease displaying microbiome dysbiosis (likely all chronic disease) could be addressed the same way:

Researchers have learned much about the effects of diet on the mucosal immune system, epithelial function, and the intestinal microbiome; these findings could have significant practical implications. Controlled studies of patients receiving enteral nutrition and observations made from patients on exclusion diets have shown that components of whole foods can have deleterious effects for patients with IBD. Additionally, studies in animal models suggested that certain nutrients can reduce intestinal inflammation. In the future, engineered diets that restrict deleterious components but supplement beneficial nutrients could be used to modify the luminal intestinal environment of patients with IBD-these might be used alone or in combination with immunosuppressive agents, or as salvage therapy for patients who do not respond or lose responsiveness to medical therapies. Stricter diets might be required to induce remission, whereas more sustainable exclusion diets could be used to maintain long-term remission. –Diet in the Pathogenesis and Treatment of Inflammatory Bowel Diseases.  Note: they did not even mention all the ubiquitous chemicals now added to the food system, speaking which…

To show the extent of microbiome impact due to diet, Georgia State University just published mice findings that an ubiquitous additive, emulsifiers,  in mice induced microbiome change associated with metabolic syndrome and IBD; these findings are being researched for broader human implications.  You can read my post on the deleterious gut impact due to emulsifiers here. The authors noted: “testing and approving food additives may not be adequate to prevent use of chemicals that promote diseases driven by low-grade inflammation and/or which will cause disease primarily in susceptible hosts”:  

Emulsifiers are added to most processed foods to aid texture and extend shelf life, can alter the gut microbiota composition and localization to induce intestinal inflammation that promotes the development of inflammatory bowel disease and metabolic syndrome, new research shows… The team fed mice two very commonly used emulsifiers, polysorbate 80 and carboxymethylcellulsose, at doses seeking to model the broad consumption of the numerous emulsifiers that are incorporated into almost all processed foods.  Science Daily, Widely used food additives promotes colitis, obesity and metabolic syndrome, shows study of emulsifiers, study at Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome.

They looked at [the mice] guts under a microscope and saw that their mucus wall was thinner than usual, and bacteria had penetrated deep into what was once a No Microbe’s Land… The gut had also become leakier, so many microbes found their way through to the immune cells and blood vessels on the other side.  The emulsifiers also changed the communities of microbes within the rodents’ guts… rise in species that excel at triggering inflammation, and in those that eat mucus like Ruminococcus and Akkermansia. Other microbes shrank away, including groups that produce anti-inflammatory substances by digesting dietary fibre.  These changes lead to a vicious cycle of even more inflammation, even leakier guts, and even thinner mucus. The result: low-grade inflammation in normal lab mice, and a more severe form—colitis—in mutant rodents that were genetically susceptible to IBD.  After swallowing the emulsifiers, both breeds of rodents ate more food. They put on body fat and gained 10 grams in weight (on top of their normal 140). Their blood sugar levels went up. They became less sensitive to the hormone insulin. In other words, they showed many symptoms of metabolic syndrome—a condition that increase the risk of diabetes and heart disease. National Geographic, Food Additives Inflame Mouse Guts By Disturbing Microbes, study at Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome.

They observed that emulsifier consumption changed the species composition of the gut microbiota and did so in a manner that made it more pro-inflammatory. The altered microbiota had enhanced capacity to digest and infiltrate the dense mucus layer that lines the intestine, which is normally, largely devoid of bacteria. Alterations in bacterial species resulted in bacteria expressing more flagellin and lipopolysaccharide, which can activate pro-inflammatory gene expression by the immune system. Such changes in bacteria triggered chronic colitis in mice genetically prone to this disorder, due to abnormal immune systems. In contrast, in mice with normal immune systems, emulsifiers induced low-grade or mild intestinal inflammation and metabolic syndrome, characterized by increased levels of food consumption, obesity, hyperglycemia and insulin resistance. “We do not disagree with the commonly held assumption that over-eating is a central cause of obesity and metabolic syndrome,” Gewirtz says. “Rather, our findings reinforce the concept suggested by earlier work that low-grade inflammation resulting from an altered microbiota can be an underlying cause of excess eating.”  Science Daily, Widely used food additives promotes colitis, obesity and metabolic syndrome, shows study of emulsifiers, study at Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome.

The majority of the intestinal bacteria belong to two phyla, the Bacteroidetes and the Firmicutes (Mariat et al. 2009).  -Intestinal microbiota in human health and disease: the impact of probiotics.  Further insights into the role of Bacteroidetes and firmicutes was presented by Professor Rob Knight, week 1 class, Gut Microbiome Gut Check: Exploring the Microbiome, 2014,  instructors Professor Rob Knight, Dr. Jessica L. Metcalf, Dr. Katherine R. Amato:

Some of the  fermicutes and bacteroids role is to digest food, produce vitamins, and metabolize drugs. The composition of the microbiome determines how drugs are metabolized and if medications are toxic or not to the liver – an example is acetaminophen and liver toxicity: you need a particular group of sulfur reducing species in the gut to not have acetaminophen toxic in the liver.   “The metabolism of drugs by both intestinal bacteria and further by enterocytes leading to their systemic absorption deserves further attention and may provide valuable insights into pre-systemic drug metabolism, delivery, and toxicity… sulfation of acetaminophen in the liver competes with sulfation of p-cresol, a metabolite exclusively generated by gut bacteria… A number of other drugs that are mainly metabolized through phase II sulfation pathways and could potentially be presenting with similar issues are minoxidil, tamoxifen, and apomorphine, among others.” -The Gut Microbiome and Pre-systemic Metabolism: Current State and Evolving Research.

“We know there are over 40 different drugs that can be influenced by gut microbes… although this has been known for decades, we still don’t really understand which microbes are involved or how they might be processing these compounds... It was previously shown that in the lab E. lenta grows on the amino acid arginine and that as you supply more and more arginine, you inhibit digoxin inactivation.  Tests conducted with mice showed that animals fed a diet high in protein, and thereby arginine, had higher levels of the drug in their blood than mice fed a zero-protein diet. Our findings really emphasize the need to see if we can predict or prevent microbial drug inactivation in cardiac patients. If successful, it may be possible someday to recommend a certain diet, or to co-administer the drug with an inhibitor like arginine, ensuring a more reliable dosage.” -Bacterial blockade: How gut microbes can inactivate cardiac drugs

Intestinal microbiota in human health and disease: the impact of probiotics further explains: The phylum Bacteroidetes consists of three classes, of which the class Bacteroidetes, containing the well-known genera Bacteroides and Prevotella, is probably the most well studied. The Firmicutes is currently the largest bacterial phylum, which contains more than 200 genera. The majority of the Firmicutes detected in the GI tract fall primarily into two main groups,

• the Clostridium coccoides group (also known as Clostridium cluster XIVa) and the
• Clostridium leptum group (also referred to as Clostridium cluster IV) ( Collins et al. 1994; Mariat et al.  2009).
• Both groups contain members of the genera Clostridium, Eubacterium and Ruminococcus that are taxonomically polyphyletic.

In addition to the two phyla Bacteroidetes and Firmicutes, other phyla such as Proteobacteria, Actinobacteria, Fusobacteria, Spirochaetes, Verrucomicrobia and Lentisphaerae, have been detected (Rajilić-Stojanović et al. 2007; Zoetendal et al. 2008).-Intestinal microbiota in human health and disease: the impact of probiotics.

Although it is estimated that… between 500 and 1,000 species are resident at any one time in the GI tract, 4 divisions predominate: Firmicutes, Bacteroidetes,Proteobacteria, and Actinobacteria. Firmicutes alone constitute ~64% of the microbiota, whereas Bacteroidetes account for ~23% of the normal microbiota (4,8,9,10). The combination of species is unique in each individual, such that a “core” microbiome is difficult to define, although redundant functions are provided by overlapping genes within different bacteria (11). Recent studies indicate two to three patterns of bacterial profiles, or enterotypes, among diverse human populations, including IBD patients, with a strong dietary influence (12,13).  –Intestinal Microbes in Inflammatory Bowel Diseases. 

In summary, it is complex; see the Map of Diversity in the Human Microbiome that I received from Harvard:

Source: Intestinal Microbes in Inflammatory Bowel Diseases, http://www.nature.com/ajgsup/journal/v1/n1/full/ajgsup20124a.html

Slide source: MetaPhlAn Metagenomic, The Huttenhower Lab Department of Biostatistics Harvard School of Public Health

I don’t want you to think the solution is to eat a whole lot of something to produce a particular microbe.

 It’s all about balance, not a few ideal microbiota. Scientists still don’t really know exactly what’s in feces since in addition to bacteria there are viruses and phages and friendly parasites that haven’t even been identified yet. This is why some view FMT from a healthy donor (no mood swings, depression, overweight, disease, allergies, and they never took an antibiotic, don’t drink – smoke – or take drugs… rather incredible the pre-requisite criteria, and I’ve only listed a portion, but see Taymount in the Irish news, London Letter: Clinic pioneers treatment for gut illness) as the best since no cocktail probiotic multi strain someone invents can ever reproduce and replicate the human microbiome diversity.  It is a very complex issue which additionally would be individualized depending on your birth, environment, your diet, antibiotic, and drug use.  

I suppose this is why I prefer a whole foods diet and live whole probiotic foods (SCD lactose free yogurt and vegetable ferments) for optimizing both the abundance and diversity of the microbiome recognizing that it is long term diet that changes up the resilient microbiome. 

Other diseases that incur a drop in microbiome abundance and/or a species diversity change includes;

IBS, IBD, obesity, celiac, atopic and allergic diseases, autism, Type 1 diabetes, rheumatoid arthritis, autism, Type 2 Diabetes, and fibromyalgia. –Intestinal microbiota in human health and disease: the impact of probiotics and Intestinal Microbes in Inflammatory Bowel Diseases. The paper, Before the onset of type 1 diabetes, gut community diversity plummets and markers of inflammation increase, showed that before the onset of Type 1 Diabetes, gut community diversity plummets and markers of inflammation increase:

Why it is difficult to say who actually is in an IBD gut; or any other gut for that matter.  Just substitute IBD with your personal situation:

Kristina Campbell (microbiota science contributor for Gut Microbiota for Health and blogger at The Intestinal Gardener)  summarized the latest IBD microbiome research: The exact role of the microbiota is still unclear.  Are IBDs:

• caused by having a disrupted microbiota,
• the result of some ‘perfect storm’ of genes & microbiota, or
• do the microbiota have no causal role to play, simply changing in response to the onset of an IBD?

1. Some studies have found differences in microbiota composition between those with IBD and healthy controls – that is, certain bacteria are over-represented or missing in the IBD cohort. But these say nothing about causality (let alone accounting for variability of each person’s microbiota over time), so they’re only the beginning of the story.
2. Furthermore, geography seems important.   The study, Geographical patterns of the standing and active human gut microbiome in health and IBD examined those with IBD across European (Germany, Lithuania) and South Asia (India) countries found distinct patterns of microbes in IBD sufferers from each location, but also some microbial biomarkers for IBD that held across all geographic locations (a decrease of Faecalibacterium).
3. Another avenue of research is examining the interplay between genes and microbiota in IBD. Complex host genetics influence the microbiome in inflammatory bowel disease looked at genetic data and microbiome data from those with IBD and found that they weren’t completely independent: genes and bacteria interacted in complex ways, and both are potentially involved in causing IBDs.
4. One more factor may be important in the IBD story: what products the microbes make. As microbes go about their metabolic activities in the gut, certain byproducts may have an effect on health outcomes. Some new research, Jonathan Braun on metabotypes and IBD,  posited that everyone falls into one of two modes of metabolic activity, or ‘metabotypes’, and almost without exception, those with Crohn’s disease have metabotype two.
5. Since the microbiota are somehow involved in IBDs, FMT has emerged as a possible way to ‘reboot’ the microbiota and possibly quell symptoms. Some, as described in this article, have already been regularly self-administering FMT with good results. The scientific literature, though, has been slow in coming.  This pilot study was recently published in which Chinese doctors treated patients with refractory Crohn’s disease with a single FMT treatment and followed up for a minimum of six months. The immediate effects and high success rate of the treatment should encourage more research studies on the topic.

Other considerations for concluding F. prausnitzii (or any other microbiota) really is reduced in IBD or other diseases

The literature data on the incidence of F. prausnitzii reduction and IBD has several limitations. Most of the studies did not comment on:

1. Participants’ previous history of dysbiosis treatment such as  antibiotics, probiotics, or prebiotics which may influence the intestinal microbiota, is not considered.  Additionally, confounding factors including diet and smoking might reduce F. prausnitzii levels and faecal butyrate values are not considered.  These considerations could find a false F. prausnitzii reduction. –Association between Faecalibacterium prausnitzii and dietary fibre in colonic fermentation in healthy human subjects.
2. Organisms cultured from mucosal surfaces are significantly different from those found in stool and vary among different parts of the gastrointestinal tract.–Intestinal Dysbiosis and the Causes of Disease or here for an easier to read format.  Based on this, how does anyone ever get an accurate stool test correlation to specific disease states?  Bottom line: You can’t but there are associations that seem to be correlative;  caution is necessary as they can’t culture/PCR (i.e., gene sequencing) many components of the microbiome yet; bottom line, there’s more in the microbiome then just bacteria…. as you now know.

   

3. The probiotic studies performed in humans have almost exclusively examined the effect of probiotic administration on the composition of the faecal microbiota, whereas other niches of the GI tract have hardly been studied thus far (Table 7)… even major local changes in microbiota composition in specific niches of the GI tract might not be reflected in the faeces…. there is still a major gap in knowledge on the influence of probiotic microorganisms on the intestinal microbiota. In addition, the influence of probiotic microorganisms on mucosa-associated intestinal microbiota is also not well studied. However, these interactions are possibly of key importance in relation to disease pathogenesis, since mucosa-associated microorganisms are in more close contact with the intestinal barrier and immune system.  Administration of a given probiotic strain will result in the (temporarily) increase of that strain the GI tract, but may also change the overall composition of the intestinal microbiota and this is not restricted to the administered species.  –Intestinal microbiota in human health and disease: the impact of probiotics
4. The diminished prevalence of Firmicutes often has a concomitant increase in Proteobacteria.  What really is the ‘bad actor’ as Proteobacteria is seen increased in disease?  AIDs is found to have increased Proteobacteria, presented by Dr. Cathy Lozupone, week 5 class, Gut Microbiome Gut Check: Exploring the Microbiome, 2014.  More research is needed to examine the species and strain diversity in the GI tract, the diversity of microbial genes (microbiome) in the GI tract and the activity of these genes (mRNA, protein and metabolite production). For future probiotic research it is important to determine the level of compositional and functional microbial dysbiosis in relevant target populations and identify potential members of the healthy microbiota to counteract the dysbiosis. -Intestinal microbiota in human health and disease: the impact of probiotics

Regardless of abundance detection issues, here is why you want to support F. prausnitzii bloom:

1. It is a keynote peacemaking species:  The Scientific American article, Among Trillions of Microbes in the Gut, a Few Are Special, is a great start to understand F. prausnitzii’s role in our gut.  Appreciate how they describe this species as the keynote peacemaking species, the polar opposite of CDiff in the gut.  Perhaps the most interesting tie to the power of F. prausnitzii in the gut is the excerpt:  “In East Asian populations the gene variants associated with inflammatory bowel disease differ from the gene variants in European populations. Yet the same bacterial species—F. prausnitzii—was reduced in the guts of those in whom the disease developed. This suggested that whereas different genetic vulnerabilities might underlie the disorder, the path to disease was similar: a loss of anti-inflammatory microbes from the gut. And although Sokol suspects that other good bacteria besides F. prausnitzii exist, this similarity hinted at a potential one-size-fits-all remedy for Crohn’s and possibly other inflammatory disorders: restoration of peacekeeping microbes.”
2. We need more study of F. prausnitzii:  There is recognition that in view of the proposed role of F. prausnitzii in intestinal health, it is important to gain a better understanding of the microbial ecology of this species. It is currently unclear what major substrates, of dietary or host origin, are likely to support growth and what factors in the gut environment may influence its distribution in the intestine. –Cultured Representatives of Two Major Phylogroups of Human Colonic Faecalibacterium prausnitzii Can Utilize Pectin, Uronic Acids, and Host-Derived Substrates for Growth.
3. Indisputable benefits of F. prausnitzii:  Association between Faecalibacterium prausnitzii Reduction and Inflammatory Bowel Disease: A Meta-Analysis and Systematic Review of the Literature excluded studies where participants had used steroids, 5-ASAs, TNF-α antibody antibiotics, probiotics, or prebiotics in the last month preceding fecal sampling as this could influence the intestinal microbiota.  NOTE:  one month may not be long enough to revert the microbiome; notwithstanding, relevant citations to this review, unless otherwise noted, are:
   • F.  prausnitzii are among the most abundant gut bacteria and belongs to the Phylum of Firmicutes, clostridial cluster IV [23], a major bacterium of the Clostridium leptum group.
   •  F. prausnitzii ranges from 5–20% of the total microbiota in stools of healthy individuals [5].
   • F. prausnitzii plays an important role in providing energy to the colonocytes and maintaining the intestinal health [6]
   •  F. prausnitzii produces (as major end products of glucose fermentation) high amounts of butyrate and anti-inflammatory compounds [37].  They are considered the probiotic of the future.  Also see Lactate-Utilizing Bacteria, Isolated from Human Feces, That Produce Butyrate as a Major Fermentation Product.
   • Butyrate plays a major role in gut physiology, protection against pathogen invasion, and modulation of immune system [38].
   • Butyrate is the primary energy source for intestinal epithelial cells, which are fundamental elements for the maintenance of barrier integrity [26].  Antioxidants Keep the Potentially Probiotic but Highly Oxygen-Sensitive Human Gut Bacterium Faecalibacterium prausnitzii Alive at Ambient Air explains:   Butyrate is the most preferred energy source for colonocytes [19],[20], stimulates cell proliferation [21], and promotes mucus secretion from colonic mucosa [22]. 
   • Butyrate may contribute to the anti-inflammatory effect by inhibiting inflammatory response through inhibition of histone deacetylase activity, resulting in suppression of NF-κB activity and hyperacetylation of histones[12].  
   • F. prausnitzii could induce relatively low amounts of IL-12 and large amounts of IL-10 and Tregs in epithelial and PBMC models to restrain the progression of inflammation[39].
   • F. prausnitzii led to significantly lower IL-12 and IFN-γ production levels and higher secretion of IL-10 in vitro peripheral blood mononuclear cells [26]  F. prausnitzii exhibited anti-inflammatory effects, partly due to secreted metabolites blocking NF-κB activation and IL-8 secretion. Moreover, in vivo effects were associated with a decrease in proinflammatory colonic cytokine synthesis and with the induction of anti-inflammatory cytokine secretion. Counterbalancing dysbiosis using the commensal bacterium F. prausnitzii as a candidate probiotic agent appears to be a promising strategy in CD treatment. –Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. 
4. Reduced F. prausnitzii in IBD, Intestinal Microbes in Inflammatory Bowel Diseases. Relevant citations to this review, unless otherwise noted, are:
   • The microbiota are indeed different in healthy controls and a subset of IBD patients, including approximately three-quarters of those with Crohn’s disease and two-thirds of those with UC (10). Regardless of disease state.  Bacteria from the Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria phyla represented the vast majority of sequences identified. Sequences representative of the Bacteroidetes and Lachnospiraceae (a Firmicutes subset that includes Clostridium subsets IV and XIVA) were greatly depleted in samples from IBD patients, whereas Actinobacteria and Proteobacteria were substantially more abundant in IBD patients than in controls (P<0.001 for all comparisons), and these changes did not correlate with the treatments the patients had previously received (Figure 3):

     

   • The data suggest that dysbiosis, defined as an abnormal ratio of beneficial and aggressive bacterial species, is a key characteristic of IBD. These findings have been replicated by a number of studies, with evidence that F. prausnitzii, a prominent member of Clostridium group IV, is consistently decreased. Of considerable interest, low ileal mucosal concentrations of F. prausnitzii have been shown to predict high risk for early reactivation of ileal Crohn’s disease (15).   
   • The abundance of F. prausnitzii was decreased in IBD patients compared with healthy controls. Furthermore, the reduction of F. prausnitzii and misbalance of the intestinal microbiota are particularly higher in CD patients with ileal involvement.  Studies were excluded if participants had used steroids, 5-ASAs, TNF-α antibody antibiotics, probiotics, or prebiotics in the last month preceding fecal sampling as this could influence the intestinal microbiota. -Association between Faecalibacterium prausnitzii Reduction and Inflammatory Bowel Disease: A Meta-Analysis and Systematic Review of the Literature
   • Crohn’s patients, mainly those with ileal involvement, have been reported to exhibit diminished prevalence of Firmicutes, often with a concomitant increase in Proteobacteria  (15, 30, 60).
   • The role of the GI microbiota in driving the phenotype of disease is illustrated by a study conducted in 2010 by Willing et al. (16), in which 40 twin pairs divergent or concordant for Crohn’s disease or UC were examined by pyrosequencing 16s ribosomal RNA. Consistent with other reports, decreased microbial diversity was observed in patients with Crohn’s disease, and ileal mucosal samples had increased Enterobacteriaceae, including Escherichia coli, and Ruminococcus gnavus numbers, of which the latter has significant mucolytic activities. Among patients with ileal disease, two genera of key symbiotic bacteria were decreased, including Faecalibacterium and Roseburia (a member of the Firmicutes phylum). These genera are prominent producers of short-chain fatty acids (especially butyrate), which play a role in protecting the intestine (3 — below image is from this source):

     

   • Another inflammatory bacteria:  Mycobacterium avium subspecies paratuberculosis (MAP)—which causes chronic granulomatous enterocolitis in ruminants with features similar to IBD—has been isolated in higher frequency in humans with Crohn’s disease, although the evidence for the presence of this pathogen in these patients is inconsistent at best, with studies reporting detection rates ranging from 0 to 100% (10,19). Clinical studies of triple antimycobacterial therapy, which would be expected to clear MAP infections, have failed to show sustained response, further suggesting that this pathogen is not involved in the initiation or progression of Crohn’s disease (20).  

   • Still another inflammatory bacteria:  Better evidence links functional changes in commensal bacteria to the pathogenesis of IBD. Adherent/invasive E. coli are found in ~38% of patients with active ileal Crohn’s disease, but in a very low percentage in normal controls and of patients with colonic Crohn’s disease (21,22). In these patients, invasive E. coli was restricted to the inflamed mucosa and correlated directly with the severity of ileal disease. These bacteria contribute to inflammation by adhering to and invading epithelial cell lines and human ileal mucosa; moreover, they can persist and replicate in macrophages and secrete large quantities of tumor necrosis factor (TNF).

   • And yet another inflammatory bacteria:  B. fragilis strains, termed enterotoxigenic B. fragilis (ETBF), secretes a proinflammatory zinc-dependent metalloprotease toxin that is associated with diarrheal illnesses in children and adults. ETBF has been identified in up to 19.3% of patients with clinically active IBD (25). In animal studies, inoculation with ETBF is associated with colitis with severe inflammation and is associated with overproduction of interleukin-17 (IL-17), a central regulator of inflammation and autoimmunity (26).

   • However, for pediatric IBD, Hansen et al. reported an increase in mucosal Faecalibacterium in pediatric CD patients compared with controls, which suggested a more dynamic role for this organism than previously described in adult IBD. –Microbiota of Pediatric IBD: increased Faecalibacterium prausnitzii and reduced bacterial diversity in Crohn’s but not in ulcerative colitis. It is possible that the microbial signature of pediatric IBD is distinct from adult disease. Furthermore, the early host and microbiota response to IBD may induce proliferation of F. prausnitzii to reverse the inflammatory change, which still remains to be explained.  Reduced F. prausnitzii abundance has also been reported in colorectal cancer (1) and in the frail elderly (29, 56), leading to the suggestion that this bacterium could provide an indicator of a healthy gut microbiota.-Association between Faecalibacterium prausnitzii Reduction and Inflammatory Bowel Disease: A Meta-Analysis and Systematic Review of the Literature

Micronutrient food sources that support F. prausnitzii  bloom 

“F. prausnitzii is considered a ‘probiotic of the future’ since it produces high amounts of butyrate and anti-inflammatory compounds. However, this bacterium is highly oxygen-sensitive, making it notoriously difficult to cultivate and preserve.  F. prausnitzii considered a strict anaerobe that is highly oxygen-sensitive.  It loses its viability within 2 min after exposure to ambient air [26].  It has been unclear how it can exist in the colon in regions having relatively high oxygen tensions  nonetheless, how it could ever be commercialized today. This has so far precluded its clinical application in the treatment of patients with inflammatory bowel diseases.”  –The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron shuttle to grow at oxic–anoxic interphases   and Antioxidants Keep the Potentially Probiotic but Highly Oxygen-Sensitive Human Gut Bacterium Faecalibacterium prausnitzii Alive at Ambient Air.

A note about supplements: There is synergy in whole foods we don’t yet understand.  Always prefer whole food over supplements.  Dr. Terry Wahls has said, “When I used supplements — they slowed my decline [MS].  When I designed my food supply to get those same nutrients — my strength began to return.  The supplement studies are best used to guide how we create the food plans.”

Faecalibacterium prausnitzii uses antioxidants cysteine and riboflavin plus the cryoprotectant inulin for bloom

1. A flavin- or antioxidant rich diet supports F. prausnitzii adherence to the gut mucosa in colonic regions where oxygen diffuses from epithelial cells.  This explains F. prausnitzii presence despite being extremely oxygen sensitive.  F. prausnitzii employs an extracellular electron shuttle of flavins and thiols to transfer electrons to oxygen. Both compounds are present in the healthy human gut. Our observations may have important implications for the treatment of patients with Crohn’s disease. Several studies have demonstrated an oxidative surge in colitis that is associated with decreased concentrations of thiols (Aw, 2003; Seril et al., 2003). –The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron shuttle to grow at oxic–anoxic interphases:
   • Sources of flavin include:  dairy, plant foliage, fruits and fibers. SCD uses lactose free cheeses and SCD yogurt and is abundant in plants and fruits.
2. F. prausnitzii can grow in the presence of oxygen, provided that their growth medium contains flavins and cysteine or glutathione. The rapid shuttling of flavins through the cell envelope is a rather specialized phenomenon, as Pseudomonas species and Escherichia coli produce riboflavin but do not utilize this compound for extracellular electron transfer (von Canstein et al., 2008).  Oral supplementation of these compounds together with flavins is therefore likely to be useful in controlling the progression of colitis (Loguercio, 2003; Dryden et al., 2005; Kim et al., 2009)  Such compounds in the gut lumen promote ‘gut health’ (Kau et al., 2011) and that they may be utilized by anaerobic bacteria in niches, where an oxygen gradient exists such as the gut mucosa.
   • SCD uses bone broth which is a source of cysteine and glycine.  
   • Glutathoine is used in our body’s phase 1 detoxification and is composed of cysteine, glycine, and glutanate.  Foods that boost glutathione leveles are:  sweet potatoes, potatoes, asparagus, broccoli, squash, cabbage, avocados, citrus fruits, strawberries, watermelon, walnuts, bone broth, raw eggs, meat and organ meats, dairy – raw milk as pasturization destoys the sulfur, whey protein.
3.  F. prausnitzii can exploit flavins and oxidized thiols as redox mediators to shuttle electrons to oxygen [38]. In this way, F. prausnitzii can survive and thrive under moderately oxygenized conditions as encountered in the human gut, where oxygen diffuses in from the epithelial cell layers.  Thus, riboflavin and cysteine can be used to develop formulations that preserve viable F. prausnitzii cells under oxygenized conditions. –Antioxidants Keep the Potentially Probiotic but Highly Oxygen-Sensitive Human Gut Bacterium Faecalibacterium prausnitzii Alive at Ambient Air.  Additionally, the gut mucosa harbors considerable amounts of thiols that are secreted by colonocytes and act as antioxidants (Keshavarzian, 1992; Loguercio, 2003). –The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron shuttle to grow at oxic–anoxic interphases.
   • Sources of thiols (Dangour, 2010) include: egg yolk, dairy products and grains.  Note: SCD includes all except for grains as SCD is grain-free.
4.  Riboflavin is required for the extracellular shuttling of electrons by F. prausnitzii cells that metabolize glucose aerobically. –The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron shuttle to grow at oxic–anoxic interphases. 
   • Riboflavin (B2) food sources: Dairy products, eggs, green leafy vegetables, lean meat, legumes, milk, nuts.
5. The present study found that F. prausnitzii can be kept alive at ambient air for 24 h when formulated with the antioxidants cysteine and riboflavin plus the cryoprotectant inulin (a prebiotic).  Improved formulations were obtained by addition of the bulking agents corn starch and wheat bran. –Antioxidants Keep the Potentially Probiotic but Highly Oxygen-Sensitive Human Gut Bacterium Faecalibacterium prausnitzii Alive at Ambient Air.
   • Inulin: contained in vegetables and plants including wheat, onion, bananas, garlic and chicory.  They also stimulate the growth of intestinal bifidobacteria.  It has been estimated that Americans consume on average 1–4 g of inulin and oligofructose per day and Europeans average 3–10 g/d (Van Loo et al. 1995). –Inulin and Oligofructose: What Are They?
6. Most F. prausnitzii strains tested, Cultured Representatives of Two Major Phylogroups of Human Colonic Faecalibacterium prausnitzii Can Utilize Pectin, Uronic Acids, and Host-Derived Substrates for Growth:
   • Grew well under anaerobic conditions on apple pectin,
   • Were able to utilize uronic acids for growth, an ability previously thought to be confined to Bacteroides spp. among human colonic anaerobes. Most strains grew on N-acetylglucosamine, demonstrating an ability to utilize host-derived substrates. 
7. All strains tested were bile sensitive, showing at least 80% growth inhibition in the presence of 0.5 μg/ml bile salts, while inhibition at mildly acidic pH was strain dependent. These attributes help to explain the abundance of F. prausnitzii in the colonic community but also suggest factors in the gut environment that may limit its distribution. -Cultured Representatives of Two Major Phylogroups of Human Colonic Faecalibacterium prausnitzii Can Utilize Pectin, Uronic Acids, and Host-Derived Substrates for Growth
8. SCD ingested for 30 days, at about 80% compliance, was found to increase F. prausnitzii in IBD Crohn’s, and the microbiome remained despite a 30 day washout where trial participants ate whatever they wanted. -see the post, IBD CROHN’S: SCD INCREASED MICROBIOME DIVERSITY BUT LOW RESIDUAL DIET REDUCED DIVERSITY and the study, Analysis of Gut Microbiome and Diet Modification in Patients with Crohn’s Disease.

How the gut uses substrate for microbiota bloom

Microbial communities in the large intestine have vital roles in the regulation of gut health and pathogenesis of disease. Dietary fibers such as resistant starch, plant cell wall materials and oligosaccharides that escape digestion by host enzymes reach the colon and serve as substrates for microbial fermentation (Saulnier et al., 2009). These plant fibers have a major impact on the gut microbial ecosystem as they serve as growth substrates for gut bacteria and are fermented to short chain fatty acids (SCFAs) (Mahowald et al., 2009).  Moreover, they are rich sources of polyphenols that can act as redox mediators (Manach et al., 2004).  The major non-gaseous end products of fermentation formed in the colon are SCFAs, including acetate, propionate and butyrate (Topping and Clifton, 2001), that are important modulators of gut health.  In particular, butyrate is the preferred energy source for the colonic mucosa and has a role in the protection against colitis and colorectal cancers (Hamer et al., 2009). The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron shuttle to grow at oxic–anoxic interphases.

Different fibers create different proportions of SCFAs.  Notice pectin’s relative butyrate production (which was cited above as a F. prausnitzii food source for butyrate producers), but there are other food sources:

Ingesting probiotics and prebiotics can modulate the short-chain fatty acid (SCFA) profiles in the human colon [11]. The most abundant SCFAs are acetate, propionate and butyrate and they are detectable in human feces at ratios of 602020, respectively [18], [19]. Using ‘probiotic’ supplementation of gut microorganisms is one tool that can be used to revert microbiota dysbiosis to situations more typically encountered in healthy individuals [1], [5]–[9] [10], [11].  Common probiotic bacteria are: Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum and Bifidobacterium longum, and the yeast Saccharomyces boulardii. –Antioxidants Keep the Potentially Probiotic but Highly Oxygen-Sensitive Human Gut Bacterium Faecalibacterium prausnitzii Alive at Ambient Air.

Always —In health through awareness,

Last updated: October 2, 2018 at 11:39 am to add the Chicken Run image to locate the foods that support F.prausnitzii bloom. This update also added the link to my post on the deleterious gut impact due to emulsifiers. 

The prior Feb 10, 2017 update added the light-bulb icon in the F. prausnitzii/Butyrate section so that section can be found easier when referenced in later posts.  Prior update January 30, 2017 added lines for section breaks for easier readability.