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The De Simone Formulation is a probiotic formula and manufacturing method developed by Claudio De Simone. [1]
The De Simone Formulation has been clinically studied for a variety of health conditions since the 1990s [2] but it has been researched the most for its efficacy in the medical management of chronic intestinal conditions including irritable bowel syndrome (IBS) [3] [4] and inflammatory bowel disease (IBD). [5] [6] [7] [8]
The De Simone Formulation has been the subject of lawsuits. In the United States, the 4th U.S. Circuit Court of Appeals upheld a false advertising verdict against the makers of the VSL#3 probiotic in February 2021 stating there was enough evidence to support a jury's November 2018 finding that the makers of VSL#3 had quote "reverse-engineered an imperfect copy" of De Simone's signature probiotic formulation that was sold under the brand name VSL#3 through May 2016 after he withdrew from their joint venture, VSL Pharmaceuticals Inc. According to the lawsuit, his departure was as a result of being pressured to substitute cheaper bacteria in the manufacturing process to lower production costs and raise profits. [9] Court action states that De Simone apparently refused. [10] The makers of VSL#3 were ordered to pay De Simone and ExeGi Pharma a combined total of $18 million (USD) in damages. [11] [12]
The Court also issued a permanent injunction intended to prevent claims, implied or stated, of continuity between the two different formulations. The court also cited public health and wellbeing concerns, when they blocked the makers of VSL#3 from linking their product with the original De Simone Formulation by referring to clinical studies that were executed using the De Simone Formulation prior to May 2016. [13]
On August 1, 2019, the American Gastroenterology Association (AGA), the medical association of gastroenterologists in the United States, issued a correction regarding the De Simone Formulation and VSL#3. AGA's correction stated it had referenced studies referenced in its 2019 Technical Review on the Management of Mild-to-Moderate Ulcerative Colitis that were based on the probiotic formulation previously know by the brand name VSL#3 before May 2016, but was now known by the formulation name 'De Simone Formulation'. [14] [15]
On January 24, 2022, the European Crohn's and Colitis Organization (ECCO) issued a letter to the editor of Oxford Academic's Journal of Crohn's and Colitis (JCC) stating that as a result of a court injunction, the ECCO must provide a clarification note for changes relating to VSL#3 and the De Simone Formulation in their articles that reference or studied these probiotics. [16]
Crohn's disease is a chronic inflammatory bowel disease characterized by recurrent episodes of intestinal inflammation, primarily manifesting as diarrhea and abdominal pain. Unlike ulcerative colitis, inflammation can occur anywhere in the gastrointestinal tract, though it most frequently affects the ileum and colon, involving all layers of the intestinal wall. Symptoms may be non-specific and progress gradually, often delaying diagnosis. About one-third of patients have colonic disease, another third have ileocolic disease, and the remaining third have isolated ileal disease. Systemic symptoms such as chronic fatigue, weight loss, and low-grade fevers are common. Organs such as the skin and joints can also be affected. Complications can include bowel obstructions, fistulas, nutrition problems, and an increased risk of intestinal cancers.
Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBD), with the other type being Crohn's disease. It is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and anemia may also occur. Often, symptoms come on slowly and can range from mild to severe. Symptoms typically occur intermittently with periods of no symptoms between flares. Complications may include abnormal dilation of the colon (megacolon), inflammation of the eye, joints, or liver, and colon cancer.
Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine, as well as the mouth, esophagus, stomach and the anus, whereas UC primarily affects the colon and the rectum.
Colitis is swelling or inflammation of the large intestine (colon). Colitis may be acute and self-limited or long-term. It broadly fits into the category of digestive diseases.
Mesalazine, also known as mesalamine or 5-aminosalicylic acid (5-ASA), is a medication used to treat inflammatory bowel disease, including ulcerative colitis and Crohn's disease. It is generally used for mildly to moderately severe disease. It is taken by mouth or rectally. The formulations which are taken by mouth appear to be similarly-effective.
In medicine, the ileal pouch–anal anastomosis (IPAA), also known as restorative proctocolectomy (RPC), ileal-anal reservoir (IAR), an ileo-anal pouch, ileal-anal pullthrough, or sometimes referred to as a J-pouch, S-pouch, W-pouch, or a pelvic pouch, is an anastomosis of a reservoir pouch made from ileum to the anus, bypassing the former site of the colon in cases where the colon and rectum have been removed. The pouch retains and restores functionality of the anus, with stools passed under voluntary control of the person, preventing fecal incontinence and serving as an alternative to a total proctocolectomy with ileostomy.
Blood in stool looks different depending on how early it enters the digestive tract—and thus how much digestive action it has been exposed to—and how much there is. The term can refer either to melena, with a black appearance, typically originating from upper gastrointestinal bleeding; or to hematochezia, with a red color, typically originating from lower gastrointestinal bleeding. Evaluation of the blood found in stool depends on its characteristics, in terms of color, quantity and other features, which can point to its source, however, more serious conditions can present with a mixed picture, or with the form of bleeding that is found in another section of the tract. The term "blood in stool" is usually only used to describe visible blood, and not fecal occult blood, which is found only after physical examination and chemical laboratory testing.
Pouchitis is an umbrella term for inflammation of the ileal pouch, an artificial rectum surgically created out of ileum in patients who have undergone a proctocolectomy or total colectomy. The ileal pouch-anal anastomosis is created in the management of patients with ulcerative colitis, indeterminate colitis, familial adenomatous polyposis, cancer, or rarely, other colitides.
Microscopic colitis refers to two related medical conditions which cause diarrhea: collagenous colitis and lymphocytic colitis. Both conditions are characterized by the presence of chronic non-bloody watery diarrhea, normal appearances on colonoscopy and characteristic histopathology findings of inflammatory cells.
Collagenous colitis is an inflammatory condition of the colon. Together with the related condition lymphocytic colitis, it is a subtype of microscopic colitis, which is characterized by inflammation that specifically affects the colon, and a clinical presentation that involves watery diarrhea but a lack of rectal bleeding. Microscopic colitis does not usually cause macroscopic changes to the colon that allow a visual diagnosis during colonoscopy, instead causing microscopic changes that can be detected through histopathological examination of colonic biopsies. The nature of these microscopic changes is what differentiates collagenous from lymphocytic colitis, with the characteristic finding in collagenous colitis being depositions of collagen in the connective tissue between the colonic glands. Collagenous colitis, and microscopic colitis as a whole, is sometimes considered to be an inflammatory bowel disease (IBD) along with Crohn's disease and ulcerative colitis. However, little is known about the etiology of microscopic colitis, and so the degree of similarity to the inflammatory bowel diseases is uncertain.
Biological therapy, the use of medications called biopharmaceuticals or biologics that are tailored to specifically target an immune or genetic mediator of disease, plays a major role in the treatment of inflammatory bowel disease. Even for diseases of unknown cause, molecules that are involved in the disease process have been identified, and can be targeted for biological therapy. Many of these molecules, which are mainly cytokines, are directly involved in the immune system. Biological therapy has found a niche in the management of cancer, autoimmune diseases, and diseases of unknown cause that result in symptoms due to immune related mechanisms.
Streptococcus thermophilus formerly known as Streptococcus salivarius subsp. thermophilus is a gram-positive bacterium, and a fermentative facultative anaerobe, of the viridans group. It tests negative for cytochrome, oxidase, and catalase, and positive for alpha-hemolytic activity. It is non-motile and does not form endospores. S. thermophilus is fimbriated.
Vedolizumab, sold under the brand name Entyvio, is a monoclonal antibody medication developed by Takeda Oncology for the treatment of ulcerative colitis and Crohn's disease. It binds to integrin α4β7, blocking the α4β7 integrin results in gut-selective anti-inflammatory activity.
Enteropathic arthropathy commonly referred to as enteropathic arthritis, is a type of arthritis linked to Crohn's disease, ulcerative colitis, and chronic inflammatory bowel diseases.
Alicaforsen is an antisense oligonucleotide therapeutic that targets the messenger RNA for the production of human ICAM-1 receptor and is being developed for the treatment of acute disease flares in moderate to severe Inflammatory Bowel Disease (IBD).
Eldelumab is a fully human monoclonal antibody that targets chemokine ligand 10 (CXCL10)/Interferon-γ-inducible protein-10 (IP-10) designed for the treatment of Crohn's disease and ulcerative colitis.
Alfasigma USA, Inc. is an American medical food company, and a division of Alfasigma Group, of Bologna, Italy.
Leukocyte apheresis is a medical device therapy for the treatment of inflammation of the colon. It works by removing from the blood a group of white blood cells called activated leukocytes that play a key role in the inflammatory stages of ulcerative colitis (UC). Selectively reducing these cells in the blood helps to reduce inflammation in the colon. Leukocyte apheresis can help UC patients with chronic, grumbling disease who are either unsuitable for, intolerant of, or failing on medicines described above.
Mirikizumab, sold under the brand name Omvoh, is a monoclonal antibody used for the treatment of ulcerative colitis. It is designed to attach to interleukin-23 (IL-23) and block its activity.
Shomron Ben-Horin is an Israeli physician, a co-founder & Chief Medical Officer of Evinature, and professor of medicine at the Tel-Aviv University.