ACT supports the production and distribution of a microbial restoration product that is saving lives and driving breakthrough research.

Alleviating Human Suffering

Our hope is to save lives through microbial restoration. Through our partnership with the University of Minnesota Microbiota Therapeutics Program, our encapsulated microbial restoration product has been used to treat over 140 people suffering from recurrent Clostridioides difficile. In addition, over 450 patients have received colonoscopic Fecal Microbiota Transplants. With a greater than 90% success rate, this treatment is saving people's lives.

Driving a Research Frontier

ACT supports multidisciplinary, collaborative academic research focused on the human microbiome with one goal in mind...cures! Our research projects and interests span across many maladies including Crohn's Disease, Ulcerative Colitis, Diabetes, Clostridioides difficile, Autism, Cancer, Allergies, Obesity, Depression, and more.

Microbial Restoration Product Development Publication Coming Soon!

Dietary Factors in Sulfur Metabolism and Pathogenesis of Ulcerative Colitis.

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The biogeography of inflammation in ulcerative colitis (UC) suggests a proximal to distal concentration gradient of a toxin. Hydrogen sulfide (H2S) has long been considered one such toxin candidate, and dietary sulfur along with the abundance of sulfate reducing bacteria (SRB) were considered the primary determinants of H2S production and clinical course of UC. The metabolic milieu in the lumen of the colon, however, is the result of a multitude of factors beyond dietary sulfur intake and SRB abundance. Here we present an updated formulation of the H2S toxin hypothesis for UC pathogenesis, which strives to incorporate the interdependency of diet composition and the metabolic activity of the entire colon microbial community. Specifically, we suggest that the increasing severity of inflammation along the proximal-to-distal axis in UC is due to the dilution of beneficial factors, concentration of toxic factors, and changing detoxification capacity of the host, all of which are intimately linked to the nutrient flow from the diet.

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Dysbiosis patterns during re-induction/salvage versus induction chemotherapy for acute leukemia.

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Acute leukemia (AL) patients undergoing intensive induction chemotherapy develop severe gut dysbiosis, placing them at heightened risk for infectious complications. Some AL patients will undergo "repeat therapy" (re-induction or salvage) due to persistent or relapsed disease. We hypothesized that prior injury to the microbiome during induction may influence dysbiosis patterns during repeat therapy. Bayesian analysis of longitudinal data demonstrated larger departures of microbial communities from the pre-chemotherapy baseline during repeat therapy compared to induction. This increased ecosystem instability during repeat therapy possibly impairs colonization resistance and increases vulnerability to Enterococcus outgrowth. Microbiota restoration therapies at the end of induction or before starting subsequent therapy warrant investigation.

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Influence of short-term changes in dietary sulfur on the relative abundances of intestinal sulfate-reducing bacteria.

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High-protein diets may be linked to gut inflammation due to increased production of hydrogen sulfide (H2S), a potential toxin, as an end product of microbial fermentation in the colon by sulfidogenic sulfate-reducing bacteria (SRB). We hypothesized that dietary content of sulfur-containing amino acids (SAA) leads to variation in the relative abundances of intestinal SRB. To test this hypothesis we performed a pilot crossover study in four healthy volunteers, who consumed two interventional diets for 10-14 days, containing high or low SAA content. The results suggest that the use of dietary interventions alone may be insufficient for rapid therapeutic targeting of SRB. Nevertheless, these pilot data provide a foundation to inform future, statistically powered, studies.

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Pre-transplant recovery of microbiome diversity without recovery of the original microbiome.

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A typical treatment path for many patients with acute leukemia (AL) includes multiple rounds of chemotherapy followed by allogeneic hematopoietic cell transplantation (allo-HCT). Extensive antibiotic exposure, prolonged and repeated healthcare facility contact, nutritional changes, and gut barrier damage in these patients result in major disruptions in the gut microbial communities. Gut dysbiosis has been associated with adverse HCT outcomes including infection, graft-versus-host disease, and mortality. We suspected that prolonged exposure to multiple antibiotics during intensive chemotherapy exemplifies sustained, compounded ecosystem perturbations, contrasting with the previously reported scenario of pulse disturbance (e.g., brief exposure to a single antibiotic). Compounded perturbations often yield unanticipated consequences for the microbial ecosystem.

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Pretransplant Serum Citrulline Predicts Acute Graft-versus-Host Disease.

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Post-transplant biomarkers of acute graft-versus-host disease (aGVHD) and nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT) have been extensively studied. However, pretransplant biomarkers may provide a greater window of opportunity to intervene. We measured serum biomarkers of various aspects of gut barrier physiology before HCT (median, day –7) and 7 and 28 days post-HCT in 95 consecutive allo-HCT recipients enrolled in an open-label biorepository protocol. Biomarkers included citrulline for total functional enterocyte mass, Reg3a for antibacterial activity of the gut, and intestinal fatty acid binding protein (I-FABP) for enterocyte turnover. Compared to 16 healthy control subjects, we demonstrated that patients came to transplant with abnormal levels of all 3 biomarkers (P < .05), reflecting residual damage from prior chemotherapy.

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80% success rate in Clostridioides difficile (rCDI) patients given fecal microbiota transplant (FMT).

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Fecal microbiota transplantation (FMT) is used to introduce healthy-people’s stool into the digestive tract of a patient suffering from recurrent Clostridioides difficile infection (rCDI). “FMT involved transfer of fecal microorganisms from healthy donors to patients to correct antibiotic-induced dysbiosis, which is the primary casual risk factor for CDI in most patients”. Patients with C. difficile commonly have less gut bacterial diversity, so introducing different communities of bacteria is hypothesized to be beneficial for healing. 89 patients over time, were given 100 freeze-dried capsules with encapsulated donor material of FMT (cap-FMT). Patients were given oral antibiotic treatment (vancomycin), as typical treatment for C. difficile, until two days before taking the FMT capsules. The study concluded that 80% of the patients with recurrent Clostridioides difficile infection benefitted from the fecal microbiota transplantation (FMT).

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Antibiotics (anti-bacterials) have a negative impact on recovery after stomach surgery in mice.

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The aim of this study was to see if antibiotic treatment before an invasive stomach surgery would have an effect on the recovery rates of mice. Researchers induced obesity in mice. Half of the mice were given vertical sleeve gastrectomy (VSG) surgeries where the stomach is reduced by half the size, and half of the mice were given sham surgeries (no part of the stomach was surgically removed). Before the surgeries, half of the mice were given antibiotics. It is known that antibiotics kill off certain gut bacterial communities. All the mice who were given antibiotics before their surgeries, had altered gut microbiomes, and detrimental outcomes. Metabolic changes were negative as the mice suffered longer recovery times after surgery, trouble regulating glucose levels after eating, and increased body fat. “Results of this study implicate the intestinal microbiota as an important contributor to metabolic homeostasis and a potentially modifiable target influencing clinical outcomes following the surgery.”

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Human microbiota effectively transferred into mice models.

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The purpose of this study was to find animal models that can be used for human microbiota studies. Unfortunately, using germ-free mice to run studies on the human gut microbiota is not possible today. A one-time transplant of the human microbial community into germ-free mice creates many medical changes. This means that germ-free mice need multiple steps for engraftment/transplant of the human microbial community, which will reduce the number of medical changes in the mice. This study, from the University of Minnesota Microbiota Therapeutics Program, found a new model of introducing the human gut microbiota into germ-free mouse models. By using sequential antibiotic therapies, engraftment of the human gut bacterial profile was successful in the mice. This is an important and positive step forward in the continuation of testing in animal models, thus translating into human gut microbiota research studies.

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Encapsulated, freeze-dried microbes successfully engraft for Clostridioides difficile patients

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The purpose of this study was to see how a healthy persons’ stool would transplant into the digestive tract of Clostridioides difficile (rCDI) patients via capsule. Each person’s microbiomes have different levels of each type of bacteria. Patients were given a capsule fecal microbiota transplant and measured outcomes were bacterial compositions in the patient’s stool after FMT. The study found that there are particular types of bacteria that will repopulate inside the digestive tract of a patient. Some types of bacteria will repopulate very quickly, some will need multiple FMT treatments, and some will not repopulate. The C. difficile patients who were cured by FMT were found to have drastic changes in gut bacterial composition; due to factors such as bile acid metabolism and bacterial community composition before the FMT.

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Developed encapsulated microbiota product that is effectively treating Clostridioides difficile.

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Fecal microbiota transplantation (FMT) was used in capsule form to treat Clostridioides difficile (rCDI) patients. The FMT capsules were created through a freeze-drying procedure that preserved the donor’s gut bacteria at 100 billion cells per capsule. This procedure is revolutionary and is a new way to standardize FMT treatment in comparison to colonoscopy. Forty-nine rCDI patients were given different amounts of FMT capsules over time. 88% of the patients achieved clinical success without a reappearance of Clostridioides difficile (rCDI). After one month of the FMT treatment, patients were found to have a “normalized” fecal microbiota community; meaning that the capsules repopulated the gut bacteria that was lacking in the patients’ microbiome.

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Fecal microbiota transplant for pre-diabetic patients.

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The purpose of this study is to determine whether changing the microbial composition in the colon can improve metabolism of sugar in people who are on the verge of developing diabetes (pre-diabetics). Study participants will undergo a fecal microbiota transplantation (FMT) using material from lean donors, as well as a series of tests prior to and after the transplant. The investigators will examine any changes in fecal bacterial composition associated with FMT and determine if any observed changes have an influence on blood sugar metabolism.

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Partnered with World-Leading Researchers

ACT is partnered with the University of Minnesota Microbiota Therapeutics Program, a world leader in developing ways to repair damaged gut microbiota. Specifically, this group has developed methods to harvest intact, healthy microbiota from thoroughly screened stool donors and administer it to patients via colonoscopy or freeze-dried encapsulation. Their protocols have been adapted worldwide and have cured tens of thousands of patients suffering from intractable Clostridium difficile infections, a superbug formed from a complication of antibiotic treatments.

For questions on partnerships, please contact us at info@achievingcures.com.

University of Minnesota Microbiota Therapeutics Program

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