Pancreatic Insufficiency 

The exocrine part of the pancreas plays an important role in the digestion of food. It secretes digestive enzymes facilitating the digestion process in the small bowel (Smeets, et al., 1998). This is an important step for digestion of LCTs. In several diseases, the exocrine role of the pancreas might be disrupted. For example, this may arise in acute/chronic pancreatitis, cystic fibrosis and subsequent pancreatic resection. 

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The primary intervention in pancreatic insufficiency is enzyme replacement therapy. However, since MCTs do not need pancreatic enzymes for digestion, it is reasonable to consider them as a source of supplemental calories in these patients if needed (Symersky, Vu, & Frolich, 2002). An additional potential benefit which is less well described, has been shown in a small study with 8 chronic enzyme-sufficient pancreatitis patients. It was found that consumption of an elemental formula containing MCTs (69% of the fat content) for 10 weeks, 3 times per day, led to a significant reduction in post-prandial abdominal pain and minimal increases of CCK levels (Shea, Bishop, & Parker, 2003).​

AAD

A deeper dive in Antibiotic-Associated Diarrhea (AAD) including Clostridium difficile associated diarrhea.

Antibiotic-associated diarrhea is defined as diarrhea developing from the beginning of antibiotic treatment to 6-8 weeks after discontinuation (Liao, Chen, Wen, & Zhao, 2021). It may lead to antimicrobial prescription noncompliance and overconsumption of second-line antibiotics.

The prevalence of AAD varies between 5% and 39% in adults. There is a direct effect of the antibacterial agent on the intestinal mucosa and a strong interference on the intestinal flora ecosystem which leads to metabolic dysfunction and overgrowth of pathogens, especially Clostridium difficile.

A recent meta-analysis using 36 published randomized-controlled trials showed that probiotics can reduce the overall incidence of AAD by 38% compared to placebo. It was also shown in a subgroup analysis that using probiotics within the first 2 days of antibiotic treatment is more beneficial to prevent diarrhea (Liao, Chen, Wen, & Zhao, 2021). No serious adverse events were reported in any of the trials that were attributable to the probiotics. A small number of adverse events were reported which are mainly around nausea and bloating.

Clostridium difficile is a gram-positive spore-forming bacterium and is the main cause of AAD and pseudomembranous colitis (Liu, et al., 2020). With the emergence of hypervirulent strains, the incidence of Clostridium difficile infections increased significantly and is becoming a public health problem. The treatment with antibiotics allows the colonization and growth of C. difficile. So far, there are still a limited number of antibiotics available against Clostridium difficile. However, the use will further impact the indigenous microbiota, which allows ingested spores of Clostridium difficile to germinate and proliferate causing recurrence of the infection after the actual treatment. The mechanism of Clostridium growth is on one hand the depletion of the gut microbiota resulting in a colonization resistance. And on the other hand, antibiotic treatment promotes the germination of Clostridium by disturbing the balance of the bile acid pool of the host.

There is an urgent need for alternative approaches. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) included probiotics in the considered treatment guidelines (Debast, Bauer, Kuijper, & et al., 2014). The efficacy to prevent Clostridium difficile and mechanisms underlying the antibacterial activity are probiotic strain dependent. The probiotic mixture in S-Core FLEXCompact™ Protein Probiotics has been clinically tested for both AAD and Clostridium difficile.

CDAD

Clostridium difficile-associated diarrhea (CDAD):

Probiotics supplementation can reduce the risk of CDAD by 64% and is safe (Goldenberg, et al., 2013).

Diarrhea related to chemotherapy: Probiotics could have a preventative effect in the occurrence of diarrhea in patients receiving chemotherapy. It was shown in a meta-analysis that this effect was shown without any adverse events (Rondanelli, et al., 2017). However, caution needs to be taken that probiotics are not given to patients that are suffering from immune suppression or other conditions that could pose additional risks.

ICU post-trauma patients: Data from ongoing ICU microbiome research reveals a rapid and marked change from a healthy microbiome to disrupted microbiota (dysbiosis) in the ICU and surgical patients. The overgrowth of pathogenic bacteria in ICU is believed to contribute to nosocomial infections, sepsis, and organ failure. Probiotics may provide clinical benefits by supporting the gut epithelial barrier, generate nutritional support for these cells, change the metabolic transcriptional landscape in the host and the edification of the immune system function. Probiotics may therefore reduce the infections/sepsis, incl Clostridium difficile infections. However larger trials are needed to characterize actual ICU and patient illness-related dysbiosis and determine, and perhaps even personalize, ideal probiotic therapies (Davison & Wischmeyer, 2018).

Chyle Leaks 

Chyle is a fluid that primarily consists of LCT containing chylomicrons and lymphatic fluid. Chyle originates in the small bowel where the chylomicrons are formed and absorbed into the lymphatic system. In a normal condition, Chyle passes through the lymphatic system and enters the venous circulation via the thoracic duct. An obstruction or an injury to the lymphatic system may results in a Chyle leak into the pleural, pericardial, or peritoneal space. The common causes of Chyle leaks include neoplasia, infections, radiation, surgery and trauma. 

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While Chyle leaks dont happen often they are also not rare. In the case of surgery, the overall incidence is 1-4% depending on the type of surgery (Smoke & DeLegge, 2008). A Chyle leak may manifest in different ways. The most common ones are Chylothorax (chylous effusion) into the thoracic cavity, as a chyloperitoneum (chylous ascites) into the abdomen, as a chylopericardium around the heart, or as external draining fistula. Treatment options for Chyle leak include drainage, pharmacological treatment (e.g. octreotide), direct surgical repair and nutrition intervention. The major goals in the nutritional management of Chyle leaks is to: decrease production and flow of Chyle (allow closure of the leak if possible), replenish fluid and electrolytes losses, and prevent malnutrition. The option for nutritional management is to use a low-fat oral diet in combination with MCT oil (prevent too much LCTs) (McCray & Parrish, 2011). The nutritional management strategy can be combined with the use of pharmacological treatment such as with octreotide. Unfortunately, to date, there is no consensus when to start and stop with octreotide therapy (Das & Shah, 2010). 

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The MCT strategy is frequently used in the case of Chyle leaks. As mentioned, MCTs do not require to be transported via the lymph system and therefore serves as an alternative fat source for patients with Chyle leaks. Note that despite MCTs not needing the lymph system, a very high MCT containing diet might still lead to some medium chain fatty acid presence in the lymph fluid (Jensen, Mascioli, & Meyer, 1989). Coconut oil should not be used in the management of Chyle leaks due to the high amount of LCTs present in the oil (McCray & Parrish, 2011). Similar with the other conditions, after >2-3 weeks the patient needs a source of essential fatty acids and most likely also additional fat-soluble vitamins. It is important to monitor patients with Chyle leaks on their nutritional status. Due to variety of leaks and underlying conditions, there is no common guideline possible.

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It is very complicated to study prospectively the effect of MCT oils in patients with Chyle leaks due to the high variety of cases. Most evidence has been generated using retrospective data and case reports.

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In a retrospective study of 245 patients that underwent pancreatoduodenectomy or total pancreatectomy, 40 patients who developed a Chyle leak were placed on an MCT-containing enteral formula, until they were able to transition to a fat-free diet with oral MCT supplementation. All patients experienced a decrease in Chyle output without requiring surgical intervention or parental nutrition (Abu Hilal, Layfield, & Di Fabio, 2013). 

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Another study looked retrospectively into the efficacy of MCT supplementation in an infant population developing chylothorax after congenital heart surgery. They concluded that MCT alone was effective in 71% of the patient (17 out of 24) (Biewer, et al., 2010).

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In a recent case study, a 33-week preterm neonate with refractory congenital chylothorax was treated with octreotide and nourished with locally available skimmed milk fortified with MCT oil. The authors concluded that skimmed milk fortified with MCT oil is a cheap and safe alternative (Sahoo, Mangla, Sethi, & Thukral, 2018). A disadvantage when feeding an infant with chylothorax is the discontinuity of breast milk feeding. In a recent study, modified breast milk enriched with MCT oil (n=13) was compared to a normal MCT containing formula (n=10). The breast milk was centrifuged in order to remove the fat, mainly LCTs and after that fortified and enriched with MCT oil. The authors concluded that feeding the infants with this modified breast milk is efficient and unharmful in chylothorax patients following cardiac surgery. This protocol ensures that patients can keep getting the benefits (e.g. immunological properties) of breast milk (Neumann, Springer, Nieschke, Kostelka, & Dahnert, 2020).  A retrospective study in Austria with 34 chylothorax patients also showed that a conservative therapy approach using the proper nutritional strategy (including MCT) and medicines is successful in most patients (Hermon, et al., 2019).