Therapeutic Microbiome Manipulation

Gut Microbiome Manipulation. (Autism Focus as 2YR FMT follow-up just publd)

Last Updated on May 31, 2019 by Patricia Carter

Summary: Do yourself a favor and look over this post about gut microbiome manipulation even if your interest in microbiome is not autism or Fecal Microbiota Transplant (FMT) because the microbiome can be manipulated many ways, FMT being only one way. DIET has a major impact on microbiome, and I’m surprised that there are only three clinical trials looking at diet and autism out of the 445 clinical trials looking at diet and microbiome (as of May 28, 2019). More surprising, there’s nearly 300 clinical trails now going on that look at FMT impact to the microbiome for many of the diseases you guys have, like: IBS, T2D, MS, IBD, melanoma, cancer, depression, anxiety, obesity, metabolic syndrome, liver NAFLD, Alzheimer’s, Parkinson’s, Psoriatic Arthritis, food allergies, recurrent UTIs, Sarcoidosis, antibiotic resistance, Chronic Fatigue Syndrome, epilepsy, Sjogren’s, HIV, malnutrition…. Manipulation of the microbiome is being looked at because the microbiome is known to be altered in inflammatory ways for most all diseases, and it’s health determines your health. For autism for example, [Saghazadeh et al 2019] reported an increase in pro-inflammatory cytokines called IFN-γ, IL-1β, IL-6, and TNF-α. That’s the immune system gone rogue. Here’s the laundry list of pro-inflammatory cytokines that were found to have no significant alteration: IL-1α, IL-2, IL-2R, IL-3, IL-7, IL-8, IL-12, IL-12p40, IL-12p70, IL-15, IL-17, IL-18, IL-23, TBF-β, and TNFRI/II! Your disease will have some mix of pro-inflammatory cytokines going on and manipulating the microbiome can decrease demands on the immune system to send out these enforcers and positively affect disease state. I hope researchers include impact to cytokines in subsequent evaluation for microbiome studies. This post reports on [Kang et al 2019] which is a TWO year follow-up study of [Kang et al 2017], which was a small pilot trial that used an 8 week FMT intervention for 18 children with Autism Spectrum Disorder (ASD). They evaluated FMT impact to GI symptoms, behavior, and the gut microbiome. The conclusion of the 2019 follow-up study was that GI and behavior symptoms continued to increase or improve, and microbial diversity continued to increase and looked more similar to their donors based on 16S ribosomal RNA (rRNA) microbiome sequencing, FOLLOWING the original Microbiota Transfer Therapy (MTT) intervention. Participants still had an average of a 58% reduction in GI symptoms and a 45% decrease in ASD symptoms compared to baseline. In addition, the parents of most participants reported a slow but steady improvement in core ASD symptoms during treatment and over the next two years., and that’s why the 2 year follow-up study was done. The study suggests that the recipients didn’t retain completely the donated microbiome, but rather retained some features of it such as increased overall diversity, and increase in some important microbes such as  Bifidobacteria,  Prevotella, and Desulfovibrio while finding a NEW state. The authors note that these encouraging observations demonstrate that “intensive MTT intervention is a promising therapy for treating children with ASD who have GI problems.” They recommended future research include double-blind, placebo-controlled randomized trials with a larger cohort. Read on to learn the power of microbiome manipulation, no matter what method(s) you employ! \O/


update

***Last updated: May 31, 2019 at 9:46 am to add that the FDA granted Fast Track designation to Finch’s Full-Spectrum Microbiota® (FSM®) therapy for the treatment of children with Autism Spectrum Disorder (ASD). The study drug is Finch’s oral capsule designed to contain a diverse community of microbiota capable of restoring an unbalanced microbiome. (ScienceDaily explains: For the original study, Alexander Khoruts and Michael Sadowsky, University of Minnesota, developed the microbiota formulation and technique for collecting micrbiota from healthy, carefully-screened donors and purifying and freezing them. The technology was then licensed to Finch Therapeutics. Finch then provided financial support for the manufacturing of the therapeutic microbiota used for the study.) Link to the clinicaltrials.gov NCTtrial noted below for details. Fast Track designation is intended to facilitate development and expedite review of therapies designed to treat serious conditions and fill an unmet medical need.  The children with ASD study is not yet recruiting, but it will be a randomized Double-Blind Placebo Controlled Cross-Over Study, Phase II clinical study in 50 children with ASD (NCT03829878), Efficacy, Safety, and Tolerability Study of Oral Full-Spectrum MicrobiotaTM (CP101) in Subjects With Autism Spectrum Disorder and Associated GI Symptoms (SPROUT). The adult with ASD study is recruiting and is a Phase II randomized parallel assignment (NCT03408886), Microbiota Transfer Therapy for Adults With Autism Spectrum Disorder (ASD) Who Have Gastrointestinal Disorders (MTT-ASD). Read the comments below this post for more information.***


The microbiome is altered in most all disease. Appreciate what that REALLY means!

The gut microbiota consist of 1013 bacteria in the human intestines (that’s 10,000,000,000,000), in addition to fungi, viruses and lots of other microorganisms.

While most research focus is on how the bacterial component of the microbiome is involved with disease, little is known about how the other micro-organisms are involved!

OpenBiome was the first supplier of genetic microbiome manipulation material (called Fecal Microbiota Transplant or FMT). I spoke to Mark Smith, the CEO, in 2015, and he connected me to MIT for even more insights. Today, OpenBiome collaborates in over 36% of all the FMT trials now occurring in the U.S. –> There are actually 295 FMT studies listed on clincialtrails.gov (accessed May 28, 2019).

I recommend all listen to a recent 2019 podcast that features 2 key microbiome researchers that I follow, Amy Proal and Mike Lustgarden appearing on Life Extension Advocacy Foundation. They discuss how complicated microbiome microbial interactions are and stress that the microbiome is anything but the friendly microbiome that the media portrays it as. Rather, if it is skewed (as is true in most all disease), organisms within are not all working to your benefit. Instead some may even be actively working on destroying the immune system just in order to help promote their survival. For example, the work of [Kouwaki et al 2017] reported that the hepatitus B virus utilizes the host extracellular vesicles and microRNAs to counteract the host’s antiviral innate immune responses. Let that sink in a moment. Not to get too sciencey, but microRNAs are key mediators of your response to infection. They activate innate immune cells such as macrophages, dendritic cells, and natural killer cells.

ANOTHER virus/microbiome whammy is noted in [Kang et al 2017]: “Viruses are abundant in the gut and they may modulate… metabolic outputs of gut microbiota like they do in other environments.” We rely on the metabolic outputs of the gut microbiota to survive. Indeed, “It is precisely due to our microbiome, and the micobiota that it contains, that we are able to even live as they give us all the genes and proteins our human genome does not encode.  You can think of it as:  humans are actually the bystanders; it is the microbiota that does all of the work.”– ” Animated Life: Seeing the Invisible.”

Now you understand why it’s really important to support your immune system by targeting as many support pathways as possible.

The 2017 ASD FMT trial intervention integrated a lot of current understanding of the complexity of the microbiome. The researchers don’t know if the efficacy of their intervention was solely from one of the four noteworthy factors, or was a combination of four factors (FMT inoculation more than once with varying inoculation dose, and prep of the host microbiome for receipt of the donor microbiome using pre-antibiotics, bowel cleanse, and stomach acid suppression).


Here’s the background studies that formed the basis for the initial Microbiome Manipulation ASD FMT trial (see [Kang et al 2017] for links):
  • Mice models found that the microbiome is mechanistically linked to abnormal metabolites [those pro-inflammatory cytokine sh*t storm bein one] and behavior.
  • A child study of those having ASD found oral vancomycin antibiotic (this antibiotic is non-absorbable meaning it acts only in the gut) led to major temporary improvements in both GI and ASD symptoms. The benefits were lost within a few weeks after treatment was stopped [22]. 
  • Previous studies have shown that vancomycin [75] and proton pump inhibitors [76] significantly alter gut microbiota.
  • Children with ASD often suffer significant gastrointestinal (GI) symptoms (constipation, diarrhea, and alternating constipation/diarrhea) that correlate with ASD severity.  [67].
  • These symptoms appear to be due, in part, to dysbiotic gut microbiota [8] and perhaps their missing roles on modulating metabolites (e.g., 4-ethylphenylsulfate, indolepyruvate, and corticosterone) that affect GI function and neurobiological conditions, such as ASD and anxiety [910]. 
  • Many children with ASD often undergo increased oral antibiotic treatment during the first 3 years of life [11], which is thought to destabilize their gut microbiota [12] and open opportunities for competitive potential pathogens to contribute to ASD severity [1314]. 
  • Studies on microbiome profile for AS children conflict, but it is thought that a lack of overall beneficial bacterial microbial diversity with a consequent lower abundance of fermentative bacteria (e.g., Prevotella copri), impairs neurological health [21].
  • A mouse model ASD study supplemented Bacteroides fragilis. It was found to alter gut microbiota and blood metabolite profiles, mitigate increased gut permeability (gaps in cell-to-cell junctions), and improve ASD-associated behaviors [9]. 

Details of the intitial ASD FMT trail [Kang et al 2017]:

[Kang et al 2017] reports on clinical trial  NCT02504554 registered on ClinicalTrials.gov. The FDA limited this study to older children, 7–17 years of age, since most FMT studies have been on adults. There was very limited data and knowledge of FMT impact and usage for children. 

Details of FMT Intervention Method

[Kang et al 2017] looked at the impact for 18 children with ASD, aged 7 to 17 years, of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms. Each child participated in the study for 18 weeks total –> A 10-week MTT treatment and an 8-week follow-up observation period after the treatment stopped. 

Participant Profile. Participants in both groups (children with ASD compared to neurotypical controls) were of similar age, gender distribution, and body mass index (BMI), but the ASD group had more individuals that were delivered by C-section, used non-standard formula during infancy, and had food allergies and eczema. Children with ASD had marginally lower fiber consumption. Their mothers had significantly lower fiber consumption compared with mothers of neurotypical children. Children with ASD were breastfed significantly shorter time than neurotypical children. Consumptions on carbohydrate, fat, protein, and calorie were comparable between both groups of children. Both groups of children had a comparable number of antibiotic administrations during the first 4 years of life

The four step key intervention used was: (1) 14 days of oral vancomycin to ensure that pathogenic bacteria were profoundly suppressed. This was followed (on day 15) by 12-24 hr fasting with (2) MoviPrep, a drink that flushes the bowels, to remove most remaining gut bacteria and vancomycin. The gut microbiome was then repopulated with (3) an extended FMT (called SHGM) which compared for the initial route, two routes of administration (oral versus rectal). This was followed by a lower oral daily FMT maintenance dosage given for 7–8 weeks. They did this because the clinical experiences of team member Thomas Borody who found that only C. difficile infection is responsive to one or two FMT infusions. ALL OTHER GI CONDITIONS—originally described for ulcerative colitis [36]—required multiple infusions of donor microbiota to achieve measurable and long-lasting benefits, including those associated with ASD. And (4) a stomach acid suppressant, Prilosec (an acid pump inhibitor) was administered starting on the 12th day of vancomycin and continued until the end of the lower dosage of SHGM (for 7 to 8 weeks in total), to reduce stomach acidity and increase the survival rate of the oral transplant through the stomach. See [Kang et al 2017] for more details.

Data acquisition: Stool samples were collected on days 0, 21, 70, and 126. Fecal swabs were collected on days 0, 14, 21, 28, 42, 56, 70, 84, 98, 112, and 126. Blood samples were collected on about days 0, 19, 33, and 74. During the study participants met with the physician for an initial evaluation with follow-up evaluations on days 16, 30, and 74. Physician phone consults occurred on days 7, 21, 42, and 130 or more frequently if adverse symptoms occurred, or if families had any questions. 

Findings: At the end of the 2017 pilot study:

  • Clinical responses, gut bacteria, and phage double-stranded DNA profiles were monitored for 18 weeks.
  • GI symptoms: At the end of treatment, there was about an 80% reduction of GI symptoms with significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain.
  • Concerning impact to behavior: Significant improvement in social skill deficits, irritability, hyperactivity, lethargy, stereotypy, and aberrant speech occurred. VABS-II scoring (this evaluates adaptive behaviors like communication, daily living skills, and socialization), found that the average developmental age increased by 1.4 years
  • These improvements remained 8 weeks after treatment ended.
  • There was no significant difference in clinical outcomes between those who received the initial SHGM dose orally or rectally.
  • GI and ASD symptoms improved slowly over the 10-week MTT treatment and 8-week observation period. Contrast this to CDiff which requires 1 dose for response to occur in a few days. Thus, it appears likely that extended treatment with FMT over many weeks, as done in this study, is necessary to observe these benefits.
  • Gut microbial diversity, including potentially beneficial microbes, significantly increased after MMT. Bacterial and phage deep sequencing analyses found successful partial engraftment of donor microbiota and phage with consequent beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium , Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks).
  • This intervention shifted gut microbiota of children with ASD toward that of neurotypical children supporting the hypothesis that gut microbiota may be at least partially responsible for GI and ASD symptoms. 

The two year follow-up study to the [Kang et al 2017] pilot study. [Kang et al 2019] details are:

All of the [Kang et al 2017] 18 participants were re-evaluated two years after MTT treatment was stopped to determine whether observed improvements in behavior and GI symptoms persisted, and to ascertain the long-term impact of MTT on the gut microbiome of the study participants. 12 of 18 participants made some changes to their medication, diet, or nutritional supplements, but these changes were well documented, most were minor, and parents perceived their impact as low. Two years after FMT treatment, most participants reported:

Findings of [Kang et al 2019]:

  • Significant improvements remained in both GI and behavior symptoms as compared with baseline measurements collected at the beginning of the original 2017 open-label trial.
  • GI symptoms: There was 58% reduction in abdominal pain, indigestion, diarrhea, and constipation (Gastrointestinal Symptom Rating Scale) and 26% reduction in % days of abnormal stools (no stool, hard stool, and soft/liquid stool) (Daily Stool Record or DSR) relative to baseline, and this result is similar to what was observed at the end of treatment. This is notable because all 18 participants reported that they had had chronic GI problems (chronic constipation and/or diarrhea) since infancy, without any period of normal GI health. The degree of improvement on indigestion symptom (a sub-category of GSRS) was reduced after 2 years compared with weeks 10 and 18. 
  • ASD related symptoms were reported to have improved significantly since the end of treatment.  Percentage changes in CARS, SRS, and ABC scores were positively correlated with percent changes in GSRS scores implying that GI relief provided by MTT may ameliorate behavioral severity in children with ASD, or vice versa, or that both may be similarly impacted by another factor.  DSR had no significant correlation.
  • ASD-related symptoms had slowly, steadily improved since week 18 of the Phase 1 trial. At the two-year follow-up, using ASD diagnosis per CARS, only 17% of participants were rated as severe (compared to 83% rated as severe at the start of the trial in 2017). At the two-year follow-up, 39% were in the mild to moderate range (same as at the end of the intervention) but the percentage of participants below the ASD diagnostic cut-off scores, having minimal or no symptoms, had increased to 44%.  
  • The parent-rated Social Responsiveness Scale (SRS) assessment revealed that those scores had dropped to 47% being in the severe range (was 89% at the beginning of the trial), with 35% in the mild/moderate range and 18% below the cut-off for ASD.  Parent-rated Aberrant Behavior Checklist (ABC), total scores continued to improve, and were 35% lower relative to baseline (versus 24% lower at the end of treatment), relative to baseline. The Vineland Adaptive Behavior Scale (VABS) equivalent age continued to improve although not as quickly as during the treatment, resulting in an increase of 2.5 years over 2 years (but this is much faster than typical for the ASD population whose developmental age was only 49% of their physical age at the start of this study).
  • Changes in gut microbiota persisted at two years, including in overall community diversity and relative abundances of  Bifidobacteria  and  Prevotella. This may reflect that MTT intervention successfully transformed gut environment into a healthier status and led to a long-term benefit on GI and behavior symptoms. Their microbiomes looked more similar to their corresponding donors which suggests some engraftment of the donor microbiome into the recipients by MTT. This suggests that the recipients didn’t retain completely the donated microbiome, but rather retained some features of it such as increased overall diversity, and increase in some important microbes such as Bifidobacteria, Prevotella, and Desulfovibrio while finding a NEW state. A recent study found reduced levels of Prevotella in the oral microbiome of children with ASD32Prevotella may be involved in butyrate production33, a key nutrient for the intestinal epithelial cells34. In addition, its co-occurrence with Desulfovibrio may reflect a synergistic advantage to outcompete other commensal microbes that utilize mucin nutrients35. Mucin desulfation may contribute to an integrity of gut epithelial cells36 as well as to the improvement on GI and behavior symptoms we observed

Much still needs to be learned

The researchers note that it is still not know if most of the changes observed were due to the vancomycin, MoviPrep, Prilosec, or FMT used, or a combination of these individual factors. They said:

  • Some participants with GI symptoms that were acid-peptic in nature may have improvements on GI symptoms solely due to the administration of stomach-acid suppressant (Prilosec)40.
  • MTT may also be beneficial for children with ASD who do not have obvious GI symptoms but have low diversity of gut bacteria, as their previous study26 found that most children with ASD had low gut bacterial diversity, regardless of whether they have GI problems.
  • I can’t ignore the thought: Is Autism a Brain Disorder? – OR – A Disorder that AFFECTS THE BRAIN?Martha Herbert, MD, PhD.
  • DIET –> I really wish we knew what these children ate to support their newly transplanted microbiomes!
  • Surprisingly there are only three clinical trials looking at diet and autism out of the 445 clinical trials looking at diet and microbiome (as of May 28, 2019), and those relate to carbs, keto and A2 milk.
  • That’s a shame. I am aware that many children with ASD see benefit using Specific Carbohydrate Diet (SCD) or a similar type diet like casein-gluten-free, soy-free, carbohydrate reduction, lactose-free, Ketogenic, Paleo, GAPS, LGIT, chemical reduction, and Finegold! There’s a lot of discussion for how all these may benefit the brain and you can look over some I found informative like: Herbert, Dietary Therapies in Autism: Modulating Metabolism and Microbiome to Shift a Dynamic Encephalopathy or Laake, GFCFSF Diet. My post, Consise Summary of SCD Studies, contains many instructions and tips for How To Do the SCD.
  • The only study I found looking at SCD for autism was [Barnhill et al 2018] which reported improvements in nutrient status, GI symptoms, and behavioral domains for one ASD child with Fragile X Syndrome. I couldn’t access the full-text, but this article explains: “All food and drinks consumed over the 16 week study period was selected and monitored by a dietician to ensure it met the guidelines of the SCD protocol and was prepared by a private chef using local and organic food sources. The child did not consume any food or drinks outside of the prescribed foods provided as part of this study. Weekly counseling was provided to ensure the child had adequate nutrition intake. After 16 weeks, results indicated that the SCD protocol was well tolerated by the child and led to improvements in growth status and gastrointestinal symptoms, as well as a reduction in maladaptive behaviors such as sensory, repetitive, and ritualistic behaviors, semantic/pragmatic problems, specific fears. Results also documented an increase in adaptive behaviors such as receptive and expressive language, learning, and memory. Based on these results, more research is needed to further evaluate the use of the SCD protocol in young children with ASD and FXS and GI Concerns. Yes, indeed,diet for children with ASD, to manipule the microbiome needs studied!
  • Key researcher Paul Whitely, is active in use of the gluten-and casein-free diet for ASD. He wrote in [Whiteley et al 2013] “Although not wholly affirmative, the majority of published studies indicate statistically significant positive changes to symptom presentation following dietary intervention. In particular, changes to areas of communication, attention, and hyperactivity are detailed, despite the presence of various methodological shortcomings.” SCD is gluten-free with a modified casein component due to the aging requirement for permitted fermented dairy. Additionally, many wait months to introduce the dairy aspect of SCD.
  • And sadly, to show how behind diet, autism, and microbiome is, this [Madzhidova et al 2019] review evaluated pediatric dietary interventions looking only at gluten and casein free diet for autism. SCD (which they incorrectly considered as low Fodmap) was looked at for IBS (and not even mentioned for autism). Sigh.
  • I wrote this post in 2014 sharing diet intervention resources for autism but have not updated this information, nor can I here as this is not the focus of this post. But I believe using diet for autism is worthwhile because it can alter the microbiome beneficially and possibly work by reducing the cytokine sh*t storm mentioned next.

Conclusion:

This post continues to show support that the gut microbiome can be manipulated to induce improvement in GUT –> brain and GUT –> behavior response, here with a focus on a specific FMT intervention for children with ASD.

Realize, many trials are now going on that look at FMT impact to the microbiome for many of the diseases you guys have, like: IBS, T2D, MS, IBD, melanoma, cancer, depression, anxiety, obesity, metabolic syndrome, liver NAFLD, Alzheimer’s, Parkinson’s, Psoriatic Arthritis, food allergies, recurrent UTIs, Sarcoidosis, antibiotic resistance, Chronic Fatigue Syndrome, epilepsy, Sjogren’s, HIV, malnutrition….

That the microbiome can be manipulated with these amazing effects using FMT should give you motivation to continue optimizing your diet to manipulate and support your microbiome, for your brain’s sake too!

Best in health through awareness.

Signature2


References
  1. Surprisingly there are only three clinical trials looking at diet manipulation of the microbiome for autism (as of May 28, 2019), and those are carb, keto and A2 milk related.
  2. There are 445 clinical trials looking at diet and microbiome  (as of May 28, 2019).
  3. Clincialtrails.gov. 295 FMT studies are listed which include IBS, T2D, MS, IBD, melanoma, cancer, depression, anxiety, obesity, metabolic syndrome, liver NAFLD, Alzheimer’s, Parkinson’s, Psoriatic Arthritis,food allergies, recurrent UTIs, Sarcoidosis, antibiotic resistance, Chronic Fatigue Syndrome, epilepsy, Sjogren’s, HIV, malnutrition, and more (accessed May 28, 2019).
  4. [Saghazadeh et al 2019] A meta-analysis of pro-inflammatory cytokines in autism spectrum disorders: Effects of age, gender, and latitude.
  5. [Kang et al 2019] Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota.
  6. [Kang et al 2017] Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.
  7. [ScienceDaily 2019] This study is reported in ScienceDaily, Autism symptoms reduced nearly 50 percent two years after fecal transplant, April 9, 2019.
  8. The children with ASD study is a randomized Double-Blind Placebo Controlled Cross-Over Study, Phase II clinical study in 50 children with ASD (NCT03829878), Efficacy, Safety, and Tolerability Study of Oral Full-Spectrum MicrobiotaTM (CP101) in Subjects With Autism Spectrum Disorder and Associated GI Symptoms (SPROUT).
  9. The adult with ASD study is Phase II randomized parallel assignment (NCT03408886), Microbiota Transfer Therapy for Adults With Autism Spectrum Disorder (ASD) Who Have Gastrointestinal Disorders (MTT-ASD).
  10. OpenBiome Current FMT Studies, page accessed May 28, 2019. They are involved with only 36% of all FMT trials in the United States as well as the first and only clinical trial taking place on the African continent.
  11. Amy Proal and Mike Lustgarden appearing on Life Extension Advocacy Foundation. Microbiome podcast stressing that the microbiome is anything but the friendly microbiome that the media portrays it as. Rather, if it is skewed (as true in most all disease) the organisms within are not all working to your benefit.
  12. [Kouwaki et al 2017]  Extracellular Vesicles Deliver Host and Virus RNA and Regulate Innate Immune Response.
  13. Animated Life: Seeing the Invisible.
  14. Herbert, Dietary Therapies in Autism: Modulating Metabolism and Microbiome to Shift a Dynamic Encephalopathy.
  15. Laake, GFCFSF Diet.
  16. My post, Consise Summary of SCD Studies, contains many instructions and tips for How To Do the SCD.
  17. [Barnhill et al 2018] Brief Report: Implementation of a Specific Carbohydrate Diet for a Child with Autism Spectrum Disorder and Fragile X Syndrome [Whiteley et al 2013] Gluten- and casein-free dietary intervention for autism spectrum conditions.
  18. The Jonson Center, 2018, New Research on the Use of Specific Carbohydrate Diet (SCD) in a Child with ASD, FXS, & GI Issues.
  19. [Whiteley et al 2013] Gluten- and casein-free dietary intervention for autism spectrum conditions.
  20. [Madzhidova et al 2019] The Use of Dietary Interventions in Pediatric Patients report looked only at gluten and casein free diet for autism, and SCD (low Fodmap) for IBS (not separating the two diets and not even looking at their impact for autism. Sigh.
  21. A Professional Autism Dietary Intervention Program is a post I write in 2014 sharing diet intervention resources for autism, but I have not updated this information.
  22. Immune System, Part 1: Crash Course A&P #45 (the innate (first responder inflammatory response) video), and then Immune System, Part 2: Crash Course A&P #46 (the second annate (learner) immunity video), and then the Immune System, Part 3: Crash Course A&P #47 (the final cell mediated immune response (the cytokine talk begins at time 5:00)). And here’s a YouTube that defines cytokine roles by Dr. Maureen Richards Ph.d of Rush University Medical College.

2 thoughts on “Gut Microbiome Manipulation. (Autism Focus as 2YR FMT follow-up just publd)”

  1. Finch Therapeutics Receives Fast Track Designation for the Investigation of Full-Spectrum Microbiota as a Treatment for Children with Autism Spectrum Disorder, April 2019, https://finchtherapeutics.com/news/2019/4/29/finch-therapeutics-receives-fast-track-designation-for-the-investigation-of-full-spectrum-microbiota-as-a-treatment-for-children-with-autism-spectrum-disorder

    Finch is supporting an actively enrolling Phase II investigator-initiated clinical study evaluating the safety and efficacy of its Full-Spectrum Microbiota therapy in adults with ASD (NCT03408886, https://clinicaltrials.gov/ct2/show/NCT03408886).

    Finch also plans to conduct a randomized, placebo-controlled, Phase II clinical study in children with ASD (NCT03829878, https://clinicaltrials.gov/ct2/show/NCT03829878). In both studies, the study drug is an oral capsule designed to contain a diverse community of microbiota capable of restoring an unbalanced microbiome.

    Finch’s FSM therapy is also being evaluated in PRISM3, an actively enrolling Phase II study in patients with recurrent C. difficile infections (NCT03110133, https://clinicaltrials.gov/ct2/show/NCT03110133).

    Full-Spectrum Microbiota therapy is not approved in any country. The FDA’s Fast Track designation does not constitute or guarantee a future approval and does not alter the standards for approval.

  2. This study is reported in ScienceDaily, Autism symptoms reduced nearly 50 percent two years after fecal transplant, April 9, 2019, https://www.sciencedaily.com/releases/2019/04/190409093725.htm
    Source: Arizona State University

    The 2019 followup study now shows the benefits are extended beyond eight weeks to at least two years post-treatment. At two years post-treatment, most of the initial improvements in gut symptoms remained. Participants still had an average of a 58% reduction in GI symptoms compared to baseline. Professional evaluation revealed a 45% decrease in ASD symptoms compared to baseline. In addition, the parents of most participants reported “a slow but steady improvement in core ASD symptoms.”In addition, parents reported a slow steady reduction of ASD symptoms during treatment and over the next two years. A professional evaluator found a 45% reduction in core ASD symptoms (language, social interaction and behavior) at two years post-treatment compared to before treatment began. “This is a world-first discovery that when we treated the gut bacteria in these children during our clinical trial two years ago to reset their microbiome with FMT, positive results are still continuing to be improving two years from the original treatments. I would call it the highest improvement in a cohort that anyone has achieved for autism symptoms,” said Borody.

    “It is very unusual to see steady gradual improvement after the conclusion of any treatment,” said Adams. “We only conducted the long-term follow-up study after several families told us that their child was continuing to improve significantly.” Krajmalnik-Brown stated that the data suggests that the MTT intervention transformed the gut environment into a healthier status, leading to long-term benefit on both GI and ASD symptoms.

    “We are finding a very strong connection between the microbes that live in our intestines and signals that travel to the brain,” said Krajmalnik-Brown, a professor at the Biodesign Swette Center for Environmental Biotechnology at the Biodesign Institute and ASU’s School for Sustainable Engineering and the Built Environment. “Two years later, the children are doing even better, which is amazing.”

    “Kids with autism are lacking important beneficial bacteria, and have fewer options in the bacterial menu of important functions that bacteria provide to the gut than typically developing kids,” Krajmalnik-Brown said.

    FMT treatment substantially increased microbial diversity and the presence of helpful bacteria in the gut, such as Bifidobacteria and Prevotella. After two years, diversity was even higher and the presence of beneficial microbes remained.

    The team is now working on optimizing the dosing and duration to try to improve benefits even more, and to determine if booster doses may be needed in some cases.

    Krajmalnik-Brown and Adams are working now on a larger placebo-controlled trial in adults with ASD to verify their results. More information on that study is available at autism.asu.edu. They also hope to do another study for children with ASD pending future funding.

    The microbiota formulation used in the original study was developed at the University of Minnesota by Alexander Khoruts and Michael Sadowsky, who developed innovative methods for collecting microbiota from healthy, carefully-screened donors and purifying and freezing them. They licensed their technology to Finch Therapeutics, who provided financial support for the manufacturing of the therapeutic microbiota used for the study.

Now I'd like to hear your thoughts... comments are always welcome!