In this study, we set out to investigate the effect of synbiotic supplementation on enteral feeding intolerance, protein status, and muscle maintenance of critically ill adult patients. The results of this study suggest that synbiotic are associated with a higher intake of hospital gavage, energy, and protein during the first four days, nitrogen balance improvement, and muscle mass maintenance in the synbiotic group.
Although enteral feed volume, energy, and protein intake increased significantly during the first four days in the synbiotic group, the overall changes were not significant and there was no difference in the total EN volume and energy or protein intake between the two groups. Our recent systematic review also showed that synbiotic, probiotic or prebiotic does not affect energy intake and feed volume in tube-fed critically ill patients (21). Although, Rushdi et al showed that prebiotic supplementation was associated with significantly increased feed volume on day 4 in the intervention group (22), which was inconsistent with our results.
Delayed gastric emptying and feeding intolerance are common in the critical care setting(23). EFI usually occurs during the first few days after the start of EN (specifically on the 3d day). The underlying mechanisms are not well-known, but it seems that elevated level of CCK and PYY and their increased response to the presence of the small amount of nutrients in the gut, inflammation, hyperglycemia, variety of medications, as well as gut microbiota dysbiosis are among the involved mechanisms (24, 25). Dysbiosis occurs within a few hours of ICU admission (26) and its effect on feeding intolerance becomes evident during the first few days. Therefore, synbiotic supplementation efficacy through its effect on gut muscle contractions, secretion and absorption, glucose homeostasis and neuro-hormonal regulations, appetite, and feeding behavior (7, 10, 11, 27), is more related to the first few days of Enteral feeding.
Nitrogen balance was significantly more negative in the synbiotic group on day 1. But, on day 14, the difference between the two groups was not statistically significant. Although the improvement of nitrogen balance was not statistically significant in either group, it was clinically remarkable in the synbiotic group. As energy and protein intake were similar in the two groups, the improvement may be attributed to the improvement of digestion and absorption of proteins in the GI tract. Some previous studies showed that probiotics can affect digestion and absorption of proteins through different mechanisms including activation of digestive protease and peptidase, improvement of absorption of small peptides and aminoamides, reduction of harmful protein fermentation. In contrast to our results, Falco de Arruda et al. showed that enteral nutrition supplemented with probiotics and glutamine was not associated with nitrogen balance improvement in head trauma patients (28).
The results of this study showed that MAC in the synbiotic group remained almost constant during the study, while it significantly decreased in the placebo group. 24-hour urine Cr and CHI, as indicators of muscle mass, also remained constant in the synbiotic group, while they decreased in the placebo group. Although this decrease was not statistically significant, the reduction of 2 kg of muscle mass in the placebo group seems to be clinically remarkable. Numerous animal studies support the effect of gut microbiota homeostasis on muscle mass maintenance (29–32), but no human study have examined this effect. According to the limited available studies, it seems that gut microbiota affects muscle pathophysiology through different mechanisms including maintenance of gut barrier function, reduction of endotoxin translocation and inflammation, improvement of insulin sensitivity, mitochondrial biogenesis, muscle anabolism, and reduction of myocyte apoptosis by important metabolites such as short- chain fatty acids (SCFAs), regulation of amino acids bioavailability for muscle protein synthesis, anabolism stimulation and oxidative stress suppression by synthesis of Vit B group, glycine, and betaine (33, 34).
To our knowledge, this is the first human clinical trial investigating the effect of synbiotic supplementation on muscle wasting in critically ill patients. Although, there are some limitations. We feed our patients with hospital gavage which contains meat protein. If we could use standard commercial gavage, we could also measure 24-hours urine 3-methyl- Histidine (3MH), which is exclusively found in the skeletal muscle, and its urinary excretion shows muscle protein degradation (35). Also, due to executive restrictions, we were not able to increase the enteral feed volume to the patients’ tolerable level and we obeyed the enteral nutrition policy of the ICU ward. Although their policy is to gradually increase EN in case of tolerance and decrease in case of intolerance, our results cannot lead to an exact conclusion about the enteral feed tolerance of our patients. Finally, we suggest further clinical trials that determine gut microbiota changes by molecular techniques.