*Marcin Jadam, Grzegorz Oracz
Small intestine bacterial overgrowth in chronic pancreatitis
Przerost bakteryjny jelita cienkiego w przewlekłym zapaleniu trzustki
Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children’s Memorial Health Institute, Warsaw
Head of Department: Professor Marek Woynarowski, MD, PhD
Przewlekłe zapalenie trzustki (PZT) jest poważną chorobą, która ma istotny wpływ na jakość życia. Konsekwencją niewydolności zewnątrz- i wewnątrzwydzielniczej trzustki są: ból brzucha, cukrzyca i niedożywienie. Czynniki predysponujące do PZT, przebieg choroby oraz czynniki jatrogenne mogą prowadzić do zaburzeń mikrobioty jelitowej. Bakteryjny przerost jelita cienkiego (ang. small intestine bacterial overgrowth – SIBO) to zwiększona liczba bakterii w jelicie cienkim. Częstość jego występowania u pacjentów z PZT wynosi około 36%. W jego przebiegu występuje wiele nieswoistych objawów, a w ciężkich przypadkach może dochodzić do biegunki tłuszczowej, niedożywienia i utraty masy ciała. Ponadto, objawy nie tylko imitują te występujące w PZT, ale często nasilają je, utrudniając leczenie. „Złotym standardem” w diagnostyce SIBO jest jakościowa i ilościowa ocena aspiratu z jelita cienkiego, ale procedura ta jest inwazyjna, kosztowna i nie wszędzie dostępna. Odpowiedzią są szeroko stosowane wodorowe testy oddechowe z glukozą. Choroba dotyczy mikrobioty jelitowej, dlatego leczenie opiera się głównie na jej modyfikacji. Rifaksymina jest najlepiej zbadanym antybiotykiem stosowanym w SIBO. Probiotyki pomagają walczyć z oportunistycznymi patogenami jelitowymi, nie powodując jednocześnie zakłóceń w ekosystemie jelit. Równie ważne jest leczenie zaburzeń odżywienia związanych z SIBO. Niezależnie od terapii, zawsze należy rozważyć ryzyko nawrotu przerostu bakteryjnego. Ze względu na rosnącą świadomość wpływu mikrobioty na przebieg wielu chorób, konieczny jest dalszy rozwój diagnostyki i leczenia jej zaburzeń, także w przewlekłym zapaleniu trzustki.
Chronic pancreatitis (CP) is a serious disease that has a significant impact on the quality of life. The consequence of exocrine and endocrine pancreatic insufficiency is an abdominal pain, diabetes mellitus and malnutrition. Factors predisposing to CP, course of disease, as well as iatrogenic factors may lead to disorders in intestinal microbiota. Small intestine bacterial overgrowth (SIBO) is excess of bacteria in the small intestine. Its prevalence in adult patients with CP is approximately 36%. Many non-specific symptoms occur in SIBO, and in severe cases, it can lead to steatorrhea, malnutrition and weight loss. Furthermore, symptoms not only imitate those occurring in CP, but often aggravate them and hinder the treatment. “Golden standard” in SIBO diagnostics is a qualitative and quantitative assessment of aspirate from the small intestine, but this procedure is invasive, expensive and not widely available. The response are commonly used hydrogen breath tests with glucose. The disorder concerns intestinal microbiota, therefore the treatment is mainly based on its modification. Rifaximin is the best studied antibiotic, used in SIBO. Probiotics help to fight opportunistic intestinal pathogens, not causing disruption in gut ecosystem. It is equally important to treat nutritional disorders associated with SIBO. Regardless of therapy, the risk of bacterial overgrowth recurrence should always be considered. Due to the increasing awareness of microbiota’s influence on the course of many diseases, it is necessary to further develop diagnostics and treatment of its disorders, also in chronic pancreatitis.
Chronic pancreatitis (CP) is an serious inflammatory process that develops in individuals with genetic, environmental and other risk factors, leading to progressive, irreversible organ injury. The disease proceeds with periods of remission and exacerbation. Gradual changes in the form of atrophy and fibrosis of pancreatic parenchyma are the cause of exocrine and subsequent endocrine pancreatic dysfunction. The consequence of this is recurring abdominal pain, which in advanced chronic pancreatitis may be constant, diabetes mellitus and malnutrition. Patients life expectancy and its quality are reduced due to progression of the disease, its association with other systemic illnesses and pancreatic cancer (1, 2).
Disturbed secretion of pancreatic juice, which apart from its essential digestive function also acts antibacterially, altered gastrointestinal motility, alcohol abuse and medicines taken in the course of CP leads to the proliferation of pathogens in the intestinal lumen. Disorders of composition, amount of bacteria in the small intestine and accompanying symptoms are defined as small intestine bacterial overgrowth (SIBO). Manifestation of this disorder include non-specific gastrointestinal symptoms such as abdominal pain, flatulence, bloating, diarrhoea and more severe complications such as vitamins and other microelements deficiencies as well as growth disorders in children. Furthermore, symptoms caused by bacterial fermentation in SIBO not only imitate those occurring in chronic pancreatitis, but often aggravate them and hinder the treatment. The problem of bacterial overgrowth affects about 1/3 of people suffering from CP (3-5).
Chronic pancreatitis is a serious disease that has a significant impact on the quality of life, which exacerbations and late sequelae can endanger patient life. In Europe, the incidence of CP range from 5 to 10 cases per 100,000 inhabitants. With median survival of 20 years, the prevalence is about 120 cases per 100,000 inhabitants. Pancreatitis is a rare childhood disease, but recent years have seen an increase in its incidence, which is explained by increased recognition (6, 7).
The causes of chronic pancreatitis, according to the TIGAR-O system, include toxic/metabolic, idiopathic, genetic, autoimmune, recurrent and severe acute pancreatitis and obstructive aetiology. Alcohol abuse remains the dominant cause of chronic pancreatitis in adults. In Western countries, it is attributed to 40-70% of all cases. Smoking is also an independent risk factor for chronic pancreatitis. Other than alcohol and tobacco etiologic factors of CP are responsible for 20-50% of remaining cases of the disease. In the paediatric population, the most common causes of CP are gene mutations, anatomical defects of the pancreatic duct, and dyslipidemia (2, 8, 9).
Recurrent episodes of acute pancreatitis and chronic inflammation cause persistent damage to the exocrine and endocrine tissues, which is the basis of chronic pancreatitis. The greater the severity of the disease, the more intense is fibrosis process and the calcification of the pancreatic parenchyma. There is a distortions of the pancreatic ducts in the form of stricture and dilatation. Regardless of origin, injury to exocrine tissue is associated with an increase in intracellular levels of activated pancreatic enzymes (also in the blood). The accompanying inflammation and stenosis of ducts can damage the surrounding endocrine cells leading to the development of carbohydrate metabolism disorders, including diabetes mellitus eventually. The consequences of exocrine insufficiency are maldigestion and malabsorption. They manifest i.a. with abdominal pain, bloating, steatorrhea, weight loss, vitamin and microelements deficiencies. In addition to the clinical picture of exocrine and endocrine failure, pain is the most debilitating and disabling symptom that occurs in the majority of patients with chronic pancreatitis.
Symptomatic treatment in CP is of primary importance. The aim of therapy is also to prevent further progression of the disease and complications. CP significantly increases the probability of developing pancreatic tumors. Where possible, risk factors that may aggravate the course of illness such as alcohol consumption or cigarette smoking should be modified. Nutritional therapy aims to improve the general condition of the patient. Changing habits will help to avoid exacerbations caused by dietary errors. In the treatment of pain apply i.a. drugs throughout the analgesic ladder, procedures to reduce the pressure in the pancreatic duct and parenchyma, invasive endoscopic and surgical methods. The latter two are also used in the prevention and treatment of complications of CP. Digestive disorders caused by exocrine insufficiency require pancreatic enzyme replacement therapy administered with meals. Carbohydrate metabolism disorders, initially, can be controlled with the help of oral hypoglycaemic drugs such as metformin. Usually, however, for the treatment of diabetes type 3c, which is associated with injury to the pancreas, insulin supplementation is required. It is recommended to use long-acting preparations along with on-demand short acting insulins (8, 10, 11).
Small intestine bacterial overgrowth
The number of microorganisms that colonize the digestive tract significantly exceeds the number of human body cells (1014 and 1013 cells, respectively). The greatest bacterial concentration is in the terminal section of the small intestine and colon (even 1012 bacteria per ml of intestinal contents). Due to the presence of mechanisms protecting against excessive microflora growth, the upper gastrointestinal tract (stomach, duodenum) has a significantly lower bacterial count (up to 103 bacteria per ml of intestinal contents). The further down, through alimentary tract, the greater the number of bacterial cells. Different conditions in each segment of the intestine cause differences not only in the number but also the type of microorganisms that inhabit them. Upper digestive tract is occupied by gastric acid-resistant organisms, such as Helicobacter pylori or Lactobacillus. Coliforms, which are Gram-negative, non-spore-forming, lactose-fermenting bacteria, are characteristic for the colon. Disorders in intestinal microbiota are called dysbiosis. Changes in the number of microorganisms, their location, or changes in the proportion of particular types of bacteria can contribute to the development of certain diseases. The definition of SIBO still evolves, but it is usually referred to as the excess of bacteria in the small intestine. A total of 105 CFU/ml (colony-forming units per ml) of aspirate is generally accepted, although some postulate lower values. Due to the imperfection of diagnostic tests, “discussion” on the diagnostic criteria is still ongoing. Prevalence of bacterial overgrowth is not easy to determine. It is detected in up to 15.6% of healthy individuals, and this number increases with age and associated illnesses (12-14).
Many mechanisms are responsible for the stability of the intestinal flora, including appropriate gastric, pancreatic juices and bile secretion, undisturbed intestinal motility, proper structure of gastrointestinal tract, especially the ileocecal valve, functioning immune system of the intestinal mucosa. Disturbance of the aforementioned mechanisms may lead to excessive bacterial colonization and development of SIBO. Changes in bowel anatomy can be congenital or acquired. Among these of intrinsic origin are the obstruction, diverticula and fistulae. The course of the digestive tract can also be changed iatrogenically as a result of surgery or postoperative sequelae. Motility disorders occur i.a. in a variety of systemic diseases or during pharmacotherapy. Parkinson’s disease, systemic sclerosis, hypothyroidism, diabetes are known to change the peristalsis and are related to the development of SIBO. Opioids, which are widely used in therapy, strongly inhibit intestinal peristaltic movements. Exocrine disorders, that influence the microbiota accompany liver cirrhosis and chronic pancreatitis. Achlorhydria occurs now, mainly due to the abuse of proton pump inhibitors. SIBO complicates also obesity, inflammatory bowel diseases, immune deficiencies, celiac disease. The relationship between SIBO and irritable bowel syndrome has not yet been clarified (13, 15).
Small intestine bacterial overgrowth is often taken into account in the differential diagnosis. This is because of the non-specific symptoms that it causes. Classic picture includes steatorrhea, abdominal pain, weight loss. However, this is not a frequent presentation. Patients are more likely to report bloating, belching, flatulence, abdominal pain and loose stools. Malnutrition and weight loss are a consequence of malabsorption, which accompany only very severe and persistent SIBO, most often associated with a change in bowel anatomy. In such cases, there may be numerous insufficiencies, not only caloric but also of fat soluble vitamins A, D, E, or B2, B6, folic acid, B12 and microelements i.a. iron. The deficiency of specific nutrients can lead to polyneuropathy, bone metabolic diseases, micro and macrocytic anaemia, and in children impairs growth and development (5, 16).
Small intestine bacterial overgrowth in chronic pancreatitis
Prevalence of SIBO in patients with CP is approximately 36%. However, considerable heterogeneity in the results of respective studies should be noted, ranging from 14-92%. To date there are no studies on the prevalence of SIBO in children with CP (4).
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