Endotoxemia is a serious complication of colic and warrants aggressive treatment. Endotoxin (lipopolysaccharide) is released from the cell wall of gram-negative bacteria when they die. Normally, endotoxin is prevented from entering systemic circulation by the barrier function of the intestinal mucosa, antibodies and enzymes which bind and neutralize it and, for the small amount that manages to enter the blood stream, removal by Kupffer cells in the liver. Endotoxemia occurs when there is an overgrowth and secondary die-off of gram negative bacteria, releasing mass quantities of endotoxin. This is especially common when the mucosal barrier is damaged, as with ischemia of the GI tract secondary to a strangulating lesion or displacement. Endotoxemia produces systemic effects such as cardiovascular shock, insulin resistance, and coagulation abnormalities.

Fluid support is essential to maintain blood pressure, often with the help of colloids or hypertonic saline. NSAIDs are commonly given to reduce systemic inflammation. However, they decrease the levels of certain prostaglandins that normally promote healing of the intestinal mucosa, which subsequently increases the amount of endotoxin absorbed. To counteract this, NSAIDs are sometimes administered with a lidocaine drip, which appears to reduce this particular negative effect. Flunixin may be used for this purpose at a dose lower than that used for analgesia, so can be safely given to a colicky horse without risking masking signs that the horse requires surgery. Other drugs that bind endotoxin, such as polymyxin B and Bio-Sponge, are also often used. Polymixin B prevents endotoxin from binding to inflammatory cells, but is potentially nephrotoxic, so should be used with caution in horses with azotemia, especially neonatal foals. Plasma may also be given with the intent of neutralizing endotoxin.

Laminitis is a major concern in horses suffering from endotoxemia. Ideally, prophylactic treatment should be provided to endotoxic horses, which includes the use of NSAIDs, DMSO, icing of the feet, and frog support. Horses are also sometimes administered heparin, which is thought to reduce the risk of laminitis by decreasing blood coagulability and thus blood clot formation in the capillaries of the foot.

Surgical intervention is nearly always required in form of exploratory laparotomy and closure of perforation with peritoneal wash. Occasionally they may be managed laparoscopically.

Conservative treatment including intravenous fluids, antibiotics, nasogastric aspiration and bowel rest is indicated only if the person is nontoxic and clinically stable.

Specific causes of colic are best managed with certain drugs. These include:

- Spasmolytic agents, most commonly Buscopan, especially in the case of gas colic.

- Pro-motility agents: metoclopramide, lidocaine, bethanechol, and erythromycin are used in cases of ileus.

- Anti-inflammatories are often used in the case of enteritis or colitis.

- Anti-microbials may be administered if an infectious agent is suspected to be the underlying cause of colic.

- Phenylephrine: used in cases of nephrosplenic entrapment to contract the spleen, and is followed by light exercise to try to shift the displaced colon back into its normal position.

- Psyllium may be given via nasogastric tube to treat sand colic.

- Anthelminthics for parasitic causes of colic.

People may be placed on a low fibre diet. It was previously thought that a low-fibre diet gives the colon adequate time to heal. Evidence tends to run counter to this with a 2011 review finding no evidence for the superiority of low fibre diets in treating diverticular disease and that a high-fibre diet may prevent diverticular disease. A systematic review published in 2012 found no high quality studies, but found that some studies and guidelines favour a high-fibre diet for the treatment of symptomatic disease. While it has been suggested that probiotics may be useful for treatment, the evidence currently neither supports nor refutes this claim.

If bacterial infection is suspected, antibiotics may be used. Despite being recommended by several guidelines, the use of antibiotics in mild cases of uncomplicated diverticulitis is supported with only "sparse and of low quality" evidence, with no evidence supporting their routine use.

If the condition does not improve, the risk of death is significant. In case of poor response to conservative therapy, a colectomy is usually required.

The objective of treatment is to decompress the bowel and to prevent swallowed air from further distending the bowel. If decompression is not achieved or the patient does not improve within 24 hours, a colectomy (surgical removal of all or part of the colon) is indicated. When surgery is required the recommended procedure is a subtotal colectomy with end ileostomy. Fluid and electrolyte replacement help to prevent dehydration and shock. Use of corticosteroids may be indicated to suppress the inflammatory reaction in the colon if megacolon has resulted from active inflammatory bowel disease. Antibiotics may be given to prevent sepsis.

Gastrointestinal perforation, also known as ruptured bowel, is a hole in the wall of part of the gastrointestinal tract. The gastrointestinal tract includes the esophagus, stomach, small intestine, and large intestine. Symptoms include severe abdominal pain and tenderness. When the hole is in the stomach or early part of the small intestine the onset of pain is typically sudden while with a hole in the large intestine onset may be more gradual. The pain is usually constant in nature. Sepsis, with an increased heart rate, increased breathing rate, fever, and confusion may occur.

The cause can include trauma such as from a knife wound, eating a sharp object, or a medical procedure such as colonoscopy, bowel obstruction such as from a volvulus, colon cancer, or diverticulitis, stomach ulcers, ischemic bowel, and a number of infections including "C. difficile". A hole allows intestinal contents to enter the abdominal cavity. The entry of bacteria results in a condition known as peritonitis or in the formation of an abscess. A hole in the stomach can also lead to a chemical peritonitis due to gastric acid. A CT scan is typically the preferred method of diagnosis; however, free air from a perforation can often be seen on plain X-ray.

Perforation anywhere along the gastrointestinal tract typically requires emergency surgery in the form of an exploratory laparotomy. This is usually carried out along with intravenous fluids and antibiotics. A number of different antibiotics may be used such as piperacillin/tazobactam or the combination of ciprofloxacin and metronidazole. Occasionally the hole can be sewn closed while other times a bowel resection is required. Even with maximum treatment the risk of death can be as high as 50%. A hole from a stomach ulcer occurs in about 1 per 10,000 people per year, while one from diverticulitis occurs in about 0.4 per 10,000 people per year.

Treatment for sigmoid volvulus may include sigmoidoscopy. If the mucosa of the sigmoid looks normal and pink, place a rectal tube for decompression, correct any fluid, electrolyte, cardiac, renal or pulmonary abnormalities and then take the person to the operating room for repair. If surgery is not performed, there is a high rate of recurrence.

For people with signs of sepsis or an abdominal catastrophe, immediate surgery and resection is advised.

Laparotomy for other forms of volvulus, especially anal volvulus.

The condition is not usually immediately life-threatening. The intussusception can be treated with either a barium or water-soluble contrast enema or an air-contrast enema, which both confirms the diagnosis of intussusception, and in most cases successfully reduces it. The success rate is over 80%. However, approximately 5–10% of these recur within 24 hours.

Cases where it cannot be reduced by an enema or the intestine is damaged require surgical reduction. In a surgical reduction, the surgeon opens the abdomen and manually squeezes (rather than pulls) the part that has telescoped. If the surgeon cannot successfully reduce it, or the bowel is damaged, they resect the affected section. More often, the intussusception can be reduced by laparoscopy, pulling the segments of intestine apart with forceps.

A high-fiber diet and fiber supplements are advisable to prevent constipation. The American Dietetic Association recommends 20–35 grams each day. Wheat bran has been shown to reduce intra colonic pressure.

The US National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) says foods such as nuts, popcorn hulls, sunflower seeds, pumpkin seeds, caraway seeds, and sesame seeds have traditionally been labeled as problem foods for people with this condition; however, no scientific data exists to prove this hypothesis. The seeds in tomatoes, zucchini, cucumbers, strawberries, raspberries, and poppy seeds, are not considered harmful by the NIDDK.

One study found that nuts and popcorn do not contribute positively or negatively to patients with diverticulosis or diverticular complications.

Intussusception may become a medical emergency if not treated early, as it eventually causes death if not reduced. In developing countries where medical hospitals are not easily accessible, especially when other problems complicate the intussusception, death becomes almost inevitable. When intussusception or any other severe medical problem is suspected, the person must be taken to a hospital immediately.

The outlook for intussusception is excellent when treated quickly, but when untreated it can lead to death within two to five days. It requires fast treatment, because the longer the intestine segment is prolapsed the longer it goes without bloodflow, and the less effective a non-surgical reduction is. Prolonged intussusception also increases the likelihood of bowel ischemia and necrosis, requiring surgical resection.

Many people with diverticulosis have minimal to no symptoms, and do not require any specific treatment. Colonic stimulants should be avoided. Treatments, like some colon cleansers, that cause hard stools, constipation, and straining, are not recommended.

Diagnostic measures can be used as interventions to help stop bleeding in some cases. Bleeding that occurs due to a neoplasm (cancer growth) can be treated using colonoscopy and clipping, surgical intervention, or other measures, depending on the form and stage of cancer. Similarly, gastric cancer is treated depending on the staging, although typically requires surgical and medical therapy.

The treatment for motility issues, namely constipation, is typically to improve the movement of waste though the GI tract. This is done by using stool softeners (which work by pulling water into the stool while in the colon), addition of fiber to the diet, and use of osmotic laxatives (which help fluid movement through the colon, improving overall motility). Improving a persons gut motility can reduce the straining during defection and decrease the risk of developing of anal fissures. Anal fissures are associated with pain and blood on the toilet paper, and require time for healing. Treatment includes topical nitrates or calcium channel blockers and surgical interventions for chronic or complex cases. Similar to anal fissures, internal hemorrhoids can cause blood on the tissue when wiping, and be felt at the opening of the anus. Treatment options for hemorrhoids can be dependent on whether an underlying cause exists. An anorectal varices related hemorrhoids caused by cirrhosis, however symptomatic treatment often involves removal.

Colitis can be divided into infectious and drug induced, as can the treatment for these conditions. With infectious colitis, treatment is pathogen dependent, and generally requires the use of antibiotics. With drug-induced colitis, treatment typically involves removal of the offending agent, as is the case in NSAID induced PUD, however, removing radiation from a cancer patient is not always practical within a treatment regimen, so medical treatment is the primary mode of treatment.

Structural compromise leading to blood in stool is caused by a variety of conditions, and therefore requires different treatment for each condition. Peptic ulcer disease alone can be divided into multiple causes, but is generally initially controlled primarily with a proton pump inhibitor, with the addition of an H blocker, or in serious cases, requiring surgical intervention. Diverticulitis and diverticulosis require antibiotic treatment, and may require surgical intervention.

Inflammatory bowel disease is also divided into separate conditions, namely ulcerative colitis and Crohn's disease, which have different medical treatment regimens, and may require surgical intervention in more serious conditions.

Distal or sigmoid, fecalomas can often be disimpacted digitally or by a catheter which carries a flow of disimpaction fluid (water or other solvent or lubricant). Surgical intervention in the form of sigmoid colectomy or proctocolectomy and ileostomy may be required only when all conservative measures of evacuation fail.

If properly treated, typical cases of surgically correctable peritonitis (e.g., perforated peptic ulcer, appendicitis, and diverticulitis) have a mortality rate of about <10% in otherwise healthy patients. The mortality rate rises to about 40% in the elderly, or in those with significant underlying illness, as well as cases that present late (after 48 hours).

Without being treated, generalised peritonitis almost always causes death. The stage magician Harry Houdini died this way, having contracted streptococcus peritonitis after his appendix ruptured and was removed too late to prevent spread of the infection.

Depending on the severity of the patient's state, the management of peritonitis may include:

- General supportive measures such as vigorous intravenous rehydration and correction of electrolyte disturbances.

- Antibiotics are usually administered intravenously, but they may also be infused directly into the peritoneum. The empiric choice of broad-spectrum antibiotics often consist of multiple drugs, and should be targeted against the most likely agents, depending on the cause of peritonitis (see above); once one or more agents are actually isolated, therapy will of course be target on them.

- Gram positive and gram negative organisms must be covered. Out of the cephalosporins, cefoxitin and cefotetan can be used to cover gram positive bacteria, gram negative bacteria, and anaerobic bacteria. Beta-lactams with beta lactamase inhibitors can also be used, examples include ampicillin/sulbactam, piperacillin/tazobactam, and ticarcillin/clavulanate. Carbapenems are also an option when treating primary peritonitis as all of the carbapenems cover gram positives, gram negatives, and anaerobes except for ertapenem. The only fluoroquinolone that can be used is moxifloxacin because this is the only fluoroquinolone that covers anaerobes. Finally, tigecycline is a tetracycline that can be used due to its coverage of gram positives and gram negatives. Empiric therapy will often require multiple drugs from different classes.

- Surgery (laparotomy) is needed to perform a full exploration and lavage of the peritoneum, as well as to correct any gross anatomical damage that may have caused peritonitis. The exception is spontaneous bacterial peritonitis, which does not always benefit from surgery and may be treated with antibiotics in the first instance.

With the exception of a few case reports describing survival without surgery, the mortality of untreated Boerhaave syndrome is nearly 100%. Its treatment includes immediate antibiotic therapy to prevent mediastinitis and sepsis, surgical repair of the perforation, and if there is significant fluid loss it should be replaced with IV fluid therapy since oral rehydration is not possible. Even with early surgical intervention (within 24 hours) the risk of death is 25%.

Organ perforation is a complete penetration of the wall of a hollow organ in the body, such as the gastrointestinal tract in the case of gastrointestinal perforation. It mainly refers to accidental or pathologic perforation, rather than intentional penetration during surgery.

Types include gastrointestinal perforation and uterine perforation.

Anemia is a common complication of blood in the stool, especially when there is a large amount of blood or bleeding occurs over a long period of time. Anemia is also commonly associated with an iron deficiency, due to the importance of iron in the formation of red blood cells (RBCs). When anemia is diagnosed as a result of blood in the stool, vitamins that are important for RBC formation (folate, vitamin B12, and vitamin C) are frequently prescribed in order to ensure that all the materials are available for those cells that are made.

A perforated ulcer, is a condition in which untreated ulcer can burn through the wall of the stomach (or other areas of the gastrointestinal tract), allowing digestive juices and food to leak into the abdominal cavity. Treatment generally requires immediate surgery. The ulcer is known initially as a peptic ulcer before the ulcer burns through the full thickness of the stomach or duodenal wall. A diagnosis is made by taking an erect abdominal/chest X-ray (seeking air under the diaphragm). This is in fact one of the very few occasions in modern times where surgery is undertaken to treat an ulcer. Many perforated ulcers have been attributed to the bacterium "Helicobacter pylori". The incidence of perforated ulcer is steadily declining, though there are still incidents where it occurs. Causes include smoking and nonsteroidal anti-inflammatory drugs (NSAIDs). A perforated ulcer can be grouped into a stercoral perforation which involves a number of different things that causes perforation of the intestine wall. The first symptom of a perforated peptic ulcer is usually sudden, severe, sharp pain in the abdomen. The experience is typically so intense that most people precisely recall the exact moment the pain began. The pain is typically at its maximum immediately and persists. It is characteristically made worse by any movement, and greatly intensifies with coughing or sneezing.

A 2002 systemic review of herbal products found that several herbs, including peppermint and caraway, have anti-dyspeptic effects for non-ulcer dyspepsia with "encouraging safety profiles". A 2004 meta-analysis of the multiple herbal extract Iberogast found it to be more effective than placebo in people with functional dyspepsia.

The role of "Helicobacter pylori" in functional dyspepsia is controversial, and no clear causal relationship has been established. This is true for both the symptom profile and pathophysiology of functional dyspepsia. Although some epidemiologic studies have suggested an association between "H. pylori" infection and functional dyspepsia, others have not. The discrepancy may stem in part from differences in methodology and lack of adequate consideration of confounding factors such as past history of peptic ulcer disease and socioeconomic status. Controlled trials disagree about whether or not "H. pylori" eradication is beneficial in functional dyspepsia, with roughly half of the trials showing improvement and the other half no improvement. In a recent multicenter U.S. trial that randomized 240 patients to treatment or placebo, and followed patients for 12 months, 28% of treated patients versus 23% of those receiving placebo reported relief of symptoms at the 12-month follow-up. Similarly, recent European trials have not shown significant differences in symptoms after "H. pylori" eradication as compared with controls. Systematic reviews of eradication have been conducted, with varying results. A systematic review in the Annals of Internal Medicine suggested no statistically significant effect, with an odds ratio (OR) for treatment success versus control of 1.29 (95% CI, 0.89–1.89; P = 0.18). Still, no effect was seen after adjusting for heterogeneity and for cure of "H. pylori". In contrast, a Cochrane review found a small but statistically significant effect in curing symptoms ("H. pylori" cure vs placebo, 36% vs 30%, respectively).

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.