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Some studies reported up to 80% of patients with irritable bowel syndrome (IBS) have SIBO (using the hydrogen breath test). Subsequent studies demonstrated statistically significant reduction in IBS symptoms following therapy for SIBO.
There is a lack of consensus however, regarding the suggested link between IBS and SIBO. Other authors concluded that the abnormal breath results so common in IBS patients do not suggest SIBO, and state that "abnormal fermentation timing and dynamics of the breath test findings support a role for abnormal intestinal bacterial distribution in IBS." There is general consensus that breath tests are abnormal in IBS; however, the disagreement lies in whether this is representative of SIBO. More research is needed to clarifiy this possible link.
Intestinal bacteria may play a causal role in the dermatological condition rosacea. A recent study subjected patients to a hydrogen breath test to detect the occurrence of SIBO. It was found that significantly more patients were hydrogen-positive than controls indicating the presence of bacterial overgrowth (47% v. 5%, p<0.001).
Hydrogen-positive patients were then given a 10-day course of rifaximin, a non-absorbable antibiotic that does not leave the digestive tract and therefore does not enter the circulation or reach the skin. 96% of patients experienced a complete remission of rosacea symptoms that lasted beyond 9 months. These patients were also negative when retested for bacterial overgrowth. In the 4% of patients that experienced relapse, it was found that bacterial overgrowth had returned. These patients were given a second course of rifaximin which again cleared rosacea symptoms and normalized hydrogen excretion.
In another study, it was found that some rosacea patients that tested hydrogen-negative were still positive for bacterial overgrowth when using a methane breath test instead. These patients showed little improvement with rifaximin, as found in the previous study, but experienced clearance of rosacea symptoms and normalization of methane excretion following administration of the antibiotic metronidazole, which is effective at targeting methanogenic intestinal bacteria.
These results suggest that optimal antibiotic therapy may vary between patients and that diverse species of intestinal bacteria appear to be capable of mediating rosacea symptoms.
This may also explain the improvement in symptoms experienced by some patients when given a reduced carbohydrate diet. Such a diet would restrict the available material necessary for bacterial fermentation and thereby reduce intestinal bacterial populations.
Antibiotic-associated diarrhea (AAD) results from an imbalance in the colonic microbiota caused by antibiotic therapy. Microbiota alteration changes carbohydrate metabolism with decreased short-chain fatty acid absorption and an osmotic diarrhea as a result. Another consequence of antibiotic therapy leading to diarrhea is overgrowth of potentially pathogenic organisms such as "Clostridium difficile". It is defined as frequent loose and watery stools with no other complications.
Meta-analyses have concluded that probiotics may protect against antibiotic-associated diarrhea in both children and adults. Evidence is insufficient, however, regarding an effect on rates of "Clostridium difficile" colitis.
However, citing conflicting data in the studies, other sources claim that the use of probiotics has failed thus far to meet the standard of medical care required for evidence-based medicine. Demonstration of the efficacy of probiotics is needed by randomized, double blind, placebo-controlled trials.
Efficacy of probiotic AAD prevention is dependent on the probiotic strain(s) used and on the dosage. Up to a 50% reduction of AAD occurrence has been found. No side-effects have been reported in any of these studies. Caution should, however, be exercised when administering probiotic supplements to immunocompromised individuals or patients who have a compromised intestinal barrier because of the risk of an infection caused by the probiotic supplements.
"Clostridium difficile", also known more commonly as "C. diff", is known to account for 10 to 20 percent of antibiotic-associated diarrhea cases. The reasoning for this, is that the antibiotics administered for the treatment of certain diseases processes such as inflammatory colitis also inadvertently kills a large portion of the gut flora, the normal flora that is usually present within the bowel. With this lower amount of "healthy" bacteria present, the overgrowth of "C. diff" is then responsible "for elaborating the enterotoxin".
Mild cases usually do not require treatment and will go away after a few days in healthy people. In cases where symptoms persist or when it is more severe, specific treatments based on the initial cause may be required.
In cases where diarrhoea is present, replenishing fluids lost is recommended, and in cases with prolonged or severe diarrhoea which persists, intravenous rehydration therapy or antibiotics may be required. A simple oral rehydration therapy (ORS) can be made by dissolving one teaspoon of salt, eight teaspoons of sugar and the juice of an orange into one litre of clean water. Studies have shown the efficacy of antibiotics in reducing the duration of the symptoms of infectious enteritis of bacterial origin, however antibiotic treatments are usually not required due to the self-limiting duration of infectious enteritis.
Bile acid sequestrants are the main agents used to treat bile acid malabsorption. Cholestyramine and colestipol, both in powder form, have been used for many years. Unfortunately many patients find them difficult to tolerate; although the diarrhea may improve, other symptoms such as pain and bloating may worsen. Colesevelam is a tablet and some patients tolerate this more easily. A proof of concept study of the farnesoid X receptor agonist obeticholic acid has shown clinical and biochemical benefit.
As of March 15, 2016, Novartis Pharmaceuticals is conducting a phase II clinical study involving a farnesoid X receptor agonist named LJN452.
The "treat empirically" route also has its difficulties, which have all come under wide debate and study. Recommendations are varied but seem to find some common ground around the notion that treatment should be individualized to the specific circumstances under which a patient has developed BLS since these circumstances affect the complex microbial make up of the affected bowel.
Tetracyclines have been the mainstay of treatment for BLS, but recent studies have concluded Rifaximin to be very effective in the treatment of BLS. One study by Di Stefano et al., however, concluded Metronidazole to be more effective than Rifaximin in the treatment of BLS.
In Germany, 90% of cases of infectious enteritis are caused by four pathogens, Norovirus, Rotavirus, "Campylobacter" and "Salmonella". Other common causes of infectious enteritis include bacteria such as "Shigella" and "E. coli," as well as viruses such as adenovirus, astrovirus and calicivirus. Other less common pathogens include "Bacillus cereus, Clostridium perfringens, Clostridium difficile" and "Staphylococcus aureus".
"Campylobacter jejuni" is one of the most common sources of infectious enteritis, and the most common bacterial pathogen found in 2 year old and smaller children with diarrhoea. It has been linked to consumption of contaminated water and food, most commonly poultry and milk. The disease tends to be less severe in developing countries, due to the constant exposure which people have with the antigen in the environment, leading to early development of antibodies.
Rotavirus is responsible for infecting 140 million people and causing 1 million deaths each year, mostly in children younger than 5 years. This makes it the most common cause of severe childhood diarrhoea and diarrhea-related deaths in the world. It selectively targets mature enterocytes in the small intestine, causing malabsorption, as well as inducing secretion of water. It has also been observed to cause villus ischemia, and increase intestinal motility. The net result of these changes is induced diarrhoea.
Enteritis necroticans is an often fatal illness, caused by β-toxin of "Clostridium perfringens". This causes inflammation and segments of necrosis throughout the gastrointestinal tract. It is most common in developing countries, however has also been documented in post-World War II Germany. Risk factors for enteritis necroticans include decreased trypsin activity, which prevent intestinal degradation of the toxin, and reduced intestinal motility, which increases likelihood of toxin accumulation.
Treatment focuses on addressing the underlying cause of symptoms.
Treatment of gastritis that leads to pernicious anemia consists of parenteral vitamin B-12 injection. Associated immune-mediated conditions (e.g., insulin dependent diabetes mellitus, autoimmune thyroiditis) should also be treated. However, treatment of these disorders has no known effect in the treatment of achlorhydria.
Achlorhydria associated with "Helicobacter pylori" infection may respond to H pylori eradication therapy, although resumption of gastric acid secretion may only be partial and it may not always reverse the condition completely.
Antimicrobial agents, including metronidazole, amoxicillin/clavulanate potassium, ciprofloxacin, and rifaximin, can be used to treat bacterial overgrowth.
Achlorhydria resulting from long-term proton-pump inhibitor (PPI) use may be treated by dose reduction or withdrawal of the PPI.
Prevention focuses on improving sanitation of water and food sources.
Treatment focuses on addressing the central components of intestinal inflammation, bacterial overgrowth and nutritional supplementation.
Surgical management is reserved for fixing anatomical causes of bowel obstruction that interfere with normal function once they are amenable to such intervention. These conditions include:
- Strictures
- Fistulae
- Diverticula
Little is known on the prognosis of achlorhydria, although there have been reports of an increased risk of gastric cancer.
A 2007 review article noted that non-"Helicobacter" bacterial species can be cultured from achlorhydric (pH > 4.0) stomachs, whereas normal stomach pH only permits the growth of "Helicobacter" species. Bacterial overgrowth may cause false positive H. Pylori test results due to the change in pH from urease activity.
Small bowel bacterial overgrowth is a chronic condition. Retreatment may be necessary once every 1–6 months. Prudent use of antibacterials now calls for an antibacterial stewardship policy to manage antibiotic resistance.
Nutritional deficiencies play a prominent role in IBD. Malabsorption, diarrhea, and GI blood loss are common features of IBD. Deficiencies of B vitamins, fat-soluble vitamins, essential fatty acids, and key minerals such as magnesium, zinc, and selenium are extremely common and benefit from replacement therapy. Dietary interventions, including certain exclusion diets, low fiber diets, and low FODMAP diets have some benefits.
Anaemia is commonly present in both ulcerative colitis and Crohn's disease. Due to raised levels of inflammatory cytokines which lead to the increased expression of hepcidin, parenteral iron is the preferred treatment option as it bypasses the gastrointestinal system, has lower incidence of adverse events and enables quicker treatment. Hepcidin itself is also an anti-inflammatory agent. In the murine model very low levels of iron restrict hepcidin synthesis, worsening the inflammation that is present. Enteral nutrition has been found to be efficient to improve hemoglobin level in patients with inflammatory bowel disease, especially combined with erythropoietin.
The oral cholera vaccine, while effective for prevention of cholera, is of questionable use for prevention of TD. A 2008 review found tentative evidence of benefit. A 2015 review stated it may be reasonable for those at high risk of complications from TD. Several vaccine candidates targeting ETEC or "Shigella" are in various stages of development.
There is evidence of an infectious contribution to inflammatory bowel disease in some patients and this subgroup of patients may benefit from antibiotic therapy.
Fecal microbiota transplant is a relatively new treatment option for IBD which has attracted attention since 2010. Some preliminary studies have suggested benefits similar to those in Clostridium difficile infection but a review of use in IBD shows that FMT is safe, but of variable efficacy. A 2014 reviewed stated that more randomized controlled trials were needed.
Secondary chronic intestinal pseudo-obstruction is managed by treating the underlying condition.
There is no cure for primary chronic intestinal pseudo-obstruction. It is important that nutrition and hydration is maintained, and pain relief is given. Drugs that increase the propulsive force of the intestines have been tried, as have different types of surgery.
Probiotics can be beneficial in the treatment of IBS; taking 10 billion to 100 billion beneficial bacteria per day is recommended for beneficial results. However, further research is needed on individual strains of beneficial bacteria for more refined recommendations. Probiotics have positive effects such as enhancing the intestinal mucosal barrier, providing a physical barrier, bacteriocin production (resulting in reduced numbers of pathogenic and gas-producing bacteria), reducing intestinal permeability and bacterial translocation, and regulating the immune system both locally and systemically among other beneficial effects. Probiotics may also have positive effects on the gut-brain axis by their positive effects countering the effects of stress on gut immunity and gut function.
A number of probiotics have been found to be effective, including "Lactobacillus plantarum", and "Bifidobacteria infantis"; but one review found only "Bifidobacteria infantis" showed efficacy. "B. infantis" may have effects beyond the gut via it causing a reduction of proinflammatory cytokine activity and elevation of blood tryptophan levels, which may cause an improvement in symptoms of depression. Some yogurt is made using probiotics that may help ease symptoms of IBS. A probiotic yeast called Saccharomyces boulardii has some evidence of effectiveness in the treatment of irritable bowel syndrome.
Certain probiotics have different effects on certain symptoms of IBS. For example, "Bifidobacterium breve", "B. longum," and "Lactobacillus acidophilus" have been found to alleviate abdominal pain. "B. breve, B. infantis, L. casei", or "L. plantarum" species alleviated distension symptoms. "B. breve, B. infantis, L. casei, L. plantarum, B. longum, L. acidophilus, L. bulgaricus", and "Streptococcus salivarius" ssp. "thermophilus" have all been found to affect flatulence levels. Most clinical studies show probiotics do not improve straining, sense of incomplete evacuation, stool consistency, fecal urgency, or stool frequency, although a few clinical studies did find some benefit of probiotic therapy. The evidence is conflicting for whether probiotics improve overall quality of life scores.
Probiotics may exert their beneficial effects on IBS symptoms via preserving the gut microbiota, normalisation of cytokine blood levels, improving the intestinal transit time, decreasing small intestine permeability, and by treating small intestinal bacterial overgrowth of fermenting bacteria.
Other preventive options include over-the-counter antidiarrhea products and antibiotics.
Bismuth subsalicylate four times daily reduces rates of traveler's diarrhea. Though many travelers find a four-times-per-day regimen inconvenient, lower doses have not been shown to be effective. Potential side effects include black tongue, black stools, nausea, constipation, and ringing in the ears. Bismuth subsalicylate should not be taken by those with aspirin allergy, kidney disease, or gout, nor concurrently with certain antibiotics such as the quinolones, and should not be taken continuously for more than three weeks. Some countries do not recommend it due to the risk of rare but serious side effects.
A hyperimmune bovine colostrum to be taken by mouth is marketed in Australia for prevention of ETEC-induced TD. As yet, no studies show efficacy under actual travel conditions.
Though effective, antibiotics are not recommended for prevention of TD in most situations because of the risk of allergy or adverse reactions to the antibiotics, and because intake of preventive antibiotics may decrease effectiveness of such drugs should a serious infection develop subsequently. Antibiotics can also cause vaginal yeast infections, or overgrowth of the bacterium "Clostridium difficile", leading to pseudomembranous colitis and its associated severe, unrelenting diarrhea.
Antibiotic prophylaxis may be warranted in special situations where benefits outweigh the above risks, such as immunocompromised travelers, chronic intestinal disorders, prior history of repeated disabling bouts of TD, or scenarios in which the onset of diarrhea might prove particularly troublesome. Options for prophylactic treatment include the quinolone antibiotics (such as ciprofloxacin), azithromycin, and trimethoprim/sulfamethoxazole, though the latter has proved less effective in recent years. Rifaximin may also be useful. Quinolone antibiotics may bind to metallic cations such as bismuth, and should not be taken concurrently with bismuth subsalicylate. Trimethoprim/sulfamethoxazole should not be taken by anyone with a history of sulfa allergy.
Prucalopride, pyridostigmine, metoclopramide, cisapride, and erythromycin may be used, but they have not been shown to have great efficacy. In such cases, treatment is aimed at managing the complications. Linaclotide is a new drug that received approval from Food and Drug Administration in August 2012 and looks promising in the treatment of chronic intestinal pseudo-obstruction, gastroparesis and inertia coli.
Intestinal stasis, which may lead to bacterial overgrowth and subsequently, diarrhea or malabsorption, is treated with antibiotics.
Nutritional deficiencies are treated by encouraging patients to avoid food high in fat and fibre, which are harder to digest and increase abdominal distention and discomfort, and have small, frequent meals (5–6 per day), focusing on liquids and soft food. Reducing intake of poorly absorbed sugar alcohols may be of benefit. Referral to an accredited dietitian is recommended. If dietary changes are unsuccessful in meeting nutritional requirements and stemming weight loss, enteral nutrition is used. Many patients eventually require parenteral nutrition.
Total parenteral nutrition (TPN) is a form of long-term nutritional treatment needed for patients that have severe pseudoobstruction. After a period of no improvement of intestinal function or motility the decision to start TPN will be made, and the surgical procedure to add a long-term, more permanent IV to administer TPN will occur. Types of IV catheters to be placed will be a PICC line or central line which include mediports, Broviac, or Hickman lines depending on how long the physicians believe the patient will require TPN. Patients that are deemed TPN dependent will require constant checkups to monitor the catheter is working properly, check liver enzyme levels and look for signs of blood infections, as catheter blockage, liver damage, and infections of catheters are the main complications associated with long term TPN use and can result in sepsis and/or additional surgeries if not properly monitored. TPN nutritional feeds are given over a period of several hours to all day infusions, and are a mixture of all the vitamins, minerals, and calories similar to what one would get eating orally daily as well as any other specific nutritional needs the patient has at the moment. TPN format is typically changed depending on loss/gain of weight and bloodwork results, and is specially formulated to meet each individual patient's needs.
Use of octreotide has been described.
Cannabis has long been known to limit or prevent nausea and vomiting from a variety of causes. This has led to extensive investigations that have revealed an important role for cannabinoids and their receptors in the regulation of nausea and emesis. With the discovery of the endocannabinoid system, novel ways to regulate both nausea and vomiting have been discovered that involve the production of endogenous cannabinoids acting centrally. The plant cannabis has been used in clinics for centuries, and has been known to be beneficial in a variety of gastrointestinal diseases, such as emesis, diarrhea, inflammatory bowel disease and intestinal pain. Moreover, modulation of the endogenous cannabinoid system in the gastrointestinal tract may provide a useful therapeutic target for gastrointestinal disorders. While some GI disorders may be controlled by diet and pharmaceutical medications, others are poorly moderated by conventional treatments. Symptoms of GI disorders often include cramping, abdominal pain, inflammation of the lining of the large and/or small intestine, chronic diarrhea, rectal bleeding and weight loss. Patients with these disorders frequently report using cannabis therapeutically.
In a 2012 animal study, cannabichromene was shown to normalize gastrointestinal hypermotility without reducing the transit time. The study notes that this result is of potential clinical interest, as the only drugs available for intestinal dysmotility are often associated with constipation.
A diet restricted in fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) now has an evidence base sufficiently strong to recommend its widespread application in conditions such as IBS and IBD. They also state the restriction of FODMAPs globally, rather than individually, controls the symptoms of functional gut disorders (e.g., IBS), and the majority of IBD patients respond just as well. It is more successful than restricting only fructose and fructans, which are also FODMAPs, as is recommended for those with fructose malabsorption. Longer-term compliance with the diet was high.
Proximal enteritis usually is managed medically. This includes nasogastric intubation every 1–2 hours to relieve gastric pressure secondary to reflux, which often produces to 2–10 L, as well as aggressive fluid support to maintain hydration and correct electrolyte imbalances. Maintaining hydration in these patients can be very challenging. In some cases, fluid support may actually increase reflux production, due to the decreased intravascular oncotic pressure from low total protein and albumin levels, leading to loss of much of these IV fluids into the intestinal lumen. These horses will often display dependent edema (edema that collects in locations based on gravity). Colloids such as plasma or Hetastarch may be needed to improve intravascular oncotic pressure, although they can be cost prohibitive for many owners. Reflux levels are monitored closely to help evaluate fluid losses, and horses recovering from DPJ show improved hydration with decreased reflux production and improved attitude.
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain relief, reduction of inflammation, and for their anti-endotoxin effects, but care must be taken since they may produce gastrointestinal ulceration and damage the kidneys. Due to a suspected link to "Clostridial" infection, anti-microbials are often administered, usually penicillin or metronidazole. Aminoglycosides should be used with extreme caution due to the risk of nephrotoxicosis (damage to the kidney). The mucosa of the intestines is damaged with DPJ, often resulting in absorption of endotoxin and risking laminitis, so therapy to combat and treat endotoxemia is often employed. This includes treatment with drugs that counteract endotoxin such as Polymyxin B and Bio-Sponge, fluid support, and laminitis prevention such as icing of the feet. Prokinetic drugs such as lidocaine, erythromycin, metoclopramide, and bethanechol are often used to treat the ileus associated with the disease.
Horses are withheld food until reflux returns to less than 1–2 L of production every 4 hours, and gut sounds return, often requiring 3–7 days of therapy. Parenteral nutrition is often provided to horses that are withheld feed for greater than 3–4 days. It is suspected to improve healing and shorten the duration of the illness, since horses often become cachexic due to the protein losing enteropathy associated with this disease.
Surgery may need to be performed to rule out colic with similar presenting signs such as obstruction or strangulation, and in cases that are long-standing (> 7 days) to perform a resection and anastomosis of the diseased bowel. However, some horses have recovered with long-term medical support (up to 20 days).
DPJ is most commonly seen in the Southeastern US, although cases have been reported throughout the United States and Canada, as well as sporadically in the United Kingdom and Europe. Horses in the Southeastern US tend to have a more severe form of the disease relative to other locations. Age, breed, and gender appear to have no effect on disease prevalence.
Symptoms of short bowel syndrome are usually addressed with medication. These include:
- Anti-diarrheal medicine (e.g. loperamide, codeine)
- Vitamin, mineral supplements and L-glutamine powder mixed with water
- H2 blocker and proton pump inhibitors to reduce stomach acid
- Lactase supplement (to improve the bloating and diarrhoea associated with lactose intolerance)
In 2004, the USFDA approved a therapy that reduces the frequency and volume of total parenteral nutrition (TPN), comprising: NutreStore (oral solution of glutamine) and Zorbtive (growth hormone, of recombinant DNA origin, for injection) together with a specialized oral diet. In 2012, an advisory panel to the USFDA voted unanimously to approve for treatment of SBS the agent teduglutide, a glucagon-like peptide-2 analog developed by NPS Pharmaceuticals, who intend to market the agent in the United States under the brandname Gattex. Teduglutide had been previously approved for use in Europe and is marketed under the brand Revestive by Nycomed.
Surgical procedures to lengthen dilated bowel include the Bianchi procedure, where the bowel is cut in half and one end is sewn to the other, and a newer procedure called serial transverse enteroplasty (STEP), where the bowel is cut and stapled in a zigzag pattern. Heung Bae Kim, MD, and Tom Jaksic, MD, both of Children's Hospital Boston, devised the STEP procedure in the early 2000s. The procedure lengthens the bowel of children with SBS and may allow children to avoid the need for intestinal transplantation. As of June 2009, Kim and Jaksic have performed 18 STEP procedures. The Bianchi and STEP procedures are usually performed by pediatric surgeons at quaternary hospitals who specialize in small bowel surgery.
There is no cure for short bowel syndrome except transplant. In newborn infants, the 4-year survival rate on parenteral nutrition is approximately 70%. In newborn infants with less than 10% of expected intestinal length, 5 year survival is approximately 20%. Some studies suggest that much of the mortality is due to a complication of the total parenteral nutrition (TPN), especially chronic liver disease. Much hope is vested in Omegaven, a type of lipid TPN feed, in which recent case reports suggest the risk of liver disease is much lower.
Although promising, small intestine transplant has a mixed success rate, with postoperative mortality rate of up to 30%. One-year and 4-year survival rate are 90% and 60%, respectively.
Treatment is directed largely towards management of underlying cause:
- Replacement of nutrients, electrolytes and fluid may be necessary. In severe deficiency, hospital admission may be required for nutritional support and detailed advice from dietitians. Use of enteral nutrition by naso-gastric or other feeding tubes may be able to provide sufficient nutritional supplementation. Tube placement may also be done by percutaneous endoscopic gastrostomy, or surgical jejunostomy. In patients whose intestinal absorptive surface is severely limited from disease or surgery, long term total parenteral nutrition may be needed.
- Pancreatic enzymes are supplemented orally in pancreatic insufficiency.
- Dietary modification is important in some conditions:
- Gluten-free diet in coeliac disease.
- Lactose avoidance in lactose intolerance.
- Antibiotic therapy to treat Small Bowel Bacterial overgrowth.
- Cholestyramine or other bile acid sequestrants will help reducing diarrhoea in bile acid malabsorption.
There are multiple large-field, multi-country research initiatives focusing on strategies to prevent and treat EE.
- The MAL-ED project
- The Alive and Thrive nutrition project
- The Sanitation, Hygiene and Infant Nutrition Efficacy (SHINE) Trial (ClinicalTrials.gov identifier: NCT01824940)
- The WASH Benefits Study