The Critical Nature of Research

The human gastrointestinal (GI) tract is home to trillions of organisms which form the complex bacterial community known as the gut microbiome.

Probiotics may increasingly be a key factor in protecting this intricate network from the disastrous effects of disease.

However, formulas vary. Successes will ultimately depend on the bacterial strains utilized, the concentration of bacteria, the way in which strains are processed, and the quality of the strains used.  

The Impact of Visbiome®

Visbiome is a highly concentrated, high potency probiotic mix of eight bacterial strains that has proven successful in the dietary management of conditions including:

Visbiome and the Dietary Management of Irritable Bowel Syndrome (IBS)

The De Simone Formulation has been the subject of clinical trials involving more than 250 adult and pediatric patients in the dietary management of dysbiosis associated with IBS.22, 23, 24, 25

IBS Study 1

For eight weeks, 25 patients with diarrhea-predominant IBS received a placebo or the De Simone Formulation.

Patients receiving the probiotic experienced a statistically significant reduction in abdominal bloating.23   

IBS Study 2

Forty-eight patients with Rome II IBS were randomized in a double-blind design to the probiotic or placebo.

Those who received the De Simone Formulation experienced a statistically significant reduction in flatulence.22 

The De Simone Formulation was well tolerated with no adverse events reported in either study. 

Visbiome and the Dietary Management of Ulcerative Colitis (UC)

Daily consumption of the De Simone Formulation has been associated with the effective dietary management of ulcerative colitis following published clinical trials involving nearly 500 adult and 47 pediatric patients. A notable study involving 32 adult patients with acute ulcerative colitis yielded a combined 77% remission/response rate with no adverse effects, as measured by Ulcerative Colitis Disease Activity Index (UCDAI) score.

Ulcerative Colitis Study 1

In a study involving 90 adult patients, the De Simone Formulation plus a low dose of the anti-inflammatory drug balsalazide proved superior to both balsalazide and mesalamine by themselves in achieving dietary management of remission and improving time to remission. 27   

Ulcerative Colitis Study 2

A second study involving 32 adult patients with acute ulcerative colitis yielded a combined 77% remission/response rate with no adverse effects, as measured by Ulcerative Colitis Disease Activity Index (UCDAI) score.26 

In the dietary management of ulcerative colitis:  

  • The De Simone Formulation helped achieve remission when added to standard therapies such as mesalazine, azathioprine, or 6-mercaptopurine.
  • In a multicenter, randomized, double-blind, placebo- controlled trial, patients consuming the De Simone Formulation had significantly higher remission rates vs. placebo (43% vs. 16%). In the same study, UCDAI scores showed a significant decrease by 50% from baseline.29

Visbiome and the Dietary Management of Pouchitis

In three double-blind, placebo-controlled trials and one open trial, the De Simone Formulation has been shown to aid in the dietary management of pouchitis.31-33

  • In Gionchetti et al. (2000), 40 patients with chronic relapsing pouchitis were randomized to the probiotic or placebo after one month of antibiotic treatment. In the dietary management of remission, 20 patients consuming the probiotic were still in remission after nine months compared to zero in the placebo group.
  • The De Simone Formulation has since been recognized as an effective tool for the dietary management of pouchitis by the American College of Gastroenterology, the German Association of Gastroenterology, the British Society of Gastroenterology, the European Crohn’s and Colitis Organization (ECCO), and The Cochrane Collaboration.34-37

Visbiome and the Dietary Management of Hepatic Encephalopathy (HE)

In the dietary management of dysbiosis associated with hepatic encephalopathy (HE), the De Simone Formulation has been the subject of multiple controlled clinical studies involving over 750 patients. In one placebo-controlled trial involving 160 cirrhotic patients, those consuming the De Simone Formulation for dysbiosis experienced a reduced incidence of HE, reduced ammonia levels, and improvements in psychometric test compared to controls. 

Hepatic Encephalopathy Study 1

In one placebo-controlled trial involving 160 cirrhotic patients, those consuming the De Simone Formulation for dysbiosis experienced a reduced incidence of HE, reduced ammonia levels, and improvements in psychometric test compared to controls. Seven patients in the probiotic group experienced overt HE compared to 14 in the control group.  

Hepatic Encephalopathy Study 2

In a second study, 235 cirrhotic patients who had prior episodes of HE were evaluated after consuming the De Simone Formulation, lactulose, or no therapy whatsoever. There was a significant difference in the development of HE in the probiotic vs. no treatment groups and in the lactulose vs. no treatment group, but no difference between the probiotic group vs. lactulose. 

Pediatric Advances  

The De Simone Formulation has been the subject of two trials involving patients between the ages of 1.7 and 17 years of age with active ulcerative colitis (UC), and another involving patients with IBS.

In the first trial, 29 patients were randomized to receive dietary management with the De Simone Formulation or placebo concomitantly with standard UC treatment (steroids, 5-ASA). Of the 29 patients, 92.8% of those treated with the De Simone Formulation and standard therapy achieved remission vs. 36.4% in the placebo arm.

Randomized Condition

Results

Dietary Management with De Simone Formulation (14 patients total)

13 patients (92.8%) achieved remission

3 patients (21.4%) relapsed within 1 year of follow-up

At 6 months, 12 months, and at time of relapse endoscopic and histological scores were significantly lower than placebo group.

Placebo Concomitantly with Standard UC Treatment (steroids, 5-ASA)

(15 patients total)

4 patients (36.4%) achieved remission.

11 patients (73.3%) relapsed within 1 year of follow-up

In the second study in pediatric patients with mild-to-moderate acute UC , the De Simone Formulation was administered open-label for eight weeks.

o Thirteen patients (56%) achieved remission.
o The combined remission/response rate was 61%. 

A third open-label study was conducted in 59 pediatric patients with irritable bowel syndrome (IBS). In this study, probiotics reduced the intensity and frequency of abdominal pain and bloating after six weeks.

Further research into such disease states will help scientists better understand their connectivity and the way Visbiome could potentially help to restore a healthy microbiome ecology.

clinical trials

ExeGi is focused on research and development of microbiome science and expanding the use of Visbiome in a variety of therapeutic areas

Human Studies - Visbiome

Disease State

Primary Endpoint

Sponsor / Collaborator

Trial Design

Estimated Enrollment

Multiple Sclerosis

Pripheral Blood Mononuclear Cells (pBMCs), Serum Neurofilament Light Concentration

Newly Diagnose Type 1 Diabetes

Controlled vs prebiotic

20

Newly Diagnose Type 1 Diabetes

Effect of Multistrain Probiotic on Imnune System Inflammation as measured by plasma transcription analysis

Medical College of Wisconsin

Single Blind Placebo Controlled

60

HIV

Blood immune activation -Percent change in blood immune activation (co-expression of CD38 and HLA-DR) on CD8 T cells at week 48

Canadian HIV Trials Network

Double Blind Placebo Controlled

40

Autism Spectrum Disorder

Changes in severity level of ASD symptomatology, Delta of scores at Autism Diagnostic Observation Schedule-2

IRCCS Stella Maris Foundation, Ministry of Health Italy,

CNR Institute of Clinical Physiology

Double Blind Placebo Controlled**

100

Autism Spectrum Disorder

Change in Autism Treatment Evaluation Checklist (ATEC) -- 12 weeks of treatment

University College, London

Double Blind Placebo Controlled

110

Cirrhosis plus Spontaneous Bacterial Peritonitis

Changes in bacterial translocation.

Changes in systemic inflammatory response and systemic oxidative damage.

Changes in cognitive function.

Foundation Research Institute of the Hospital de Sant Pau, Barcelona Spain

Double Blind Placebo Controlled**

30

Pre-Diabetic Adolescents

Change in microbiota composition

Change in microbiota composition (Secondary)

University of Seattle

Double Blind Placebo Controlled

16

Eradication of Extended Spectrum BetaLactam (ESBL) colonization in adults

Rate of participants that have changed from ESBL-negative to ESBL-negative.

Lund University

Double Blind Placebo Controlled

80

Portal Hypertension

Nocturnal systolic blood pressure -- 8 weeks

Charite University, Berlin, Germany

Double Blind Placebo Controlled

110

Severe Depression

Hamilton Depression Score

University Psychiatric Clinics, Basel, Switzerland

Double Blind Placebo Controlled

60

Human Studies – SivoBiome™   

SivoBiome™ is under clinical development but not currently commercially available in the U.S. 

Disease State

Primary Endpoint

Sponsor / Collaborator

Trial Design

Estimated Enrollment

Sivobiome™ Probiotic in Moderate Covid-19 Positive Patients Pre-ICU

Resolution of diarrhea. Progression to intubation , mortality, length of hospital stay. Patients treated concomitantly with conventional treatments (chloroquine, antibiotics, biologics)

University of Roma La Sapienza – Italy

Controlled vs standard of care without probiotic

70

Sivobiome™ and oxygen-ozone as adjuvant in early control of Covid-19 Progression

Progression to intubation despite treatment, mortality, length of hospital stay

University of Roma La Sapienza – Italy

Controlled vs standard of care without probiotic/oxygen ozone therapy

152

Veterinary Studies

Disease State

Primary Endpoint

Sponsor / Collaborator

Trial Design

Estimated Enrollment

Canine Inflammatory Bowel Disease

Dogs with IBD were randomized to receive either probiotic or combination drug therapy (Metronidazole/prednisone)

 

Evaluation with histology, CIBDAI, CD3+ cells, FoxP3+ cells, plasma, citrulline, microbiota analysis.

Texas A&M University, Iowa State University, University of Camerino (Italy)

Double Blind Randomized-Controlled

34 Dogs

Acute Hemorrhagic Diarrhea Syndrome (canine)

To evaluate the efficacy of probiotics in the treatment of acute hemorrhagic diarrheal syndrome in dogs and to characterize the changes in bacterial microbiota during the course of disease.

University of Munich

Controlled

60 Dogs

.