Acute pancreatitis (AP) in many nations is a common reason for hospitalization for gastrointestinal conditions. Due to the rising prevalence of the metabolic syndrome and hypertriglyceridemia, acute pancreatitis is becoming more common around the globe. According to several reports, hypertriglyceridemia has been linked to an increase in acute pancreatitis ( de Pretis et al., 2018; Kota et al., 2012). This condition causes pancreatic inflammation that is acute in nature. Acute pancreatitis can range in severity from mild cases that only need conservative care to severe and complicated conditions that have a high mortality and morbidity rate. Acute pancreatitis also has a variable mortality rate, ranging from 3% in individuals with mild edematous pancreatitis to 20% in those with pancreatic necrosis ( Werge et al., 2016; Gapp et al., 2023).

Previous studies have assessed the microbiome’s contribution to AP. These investigations describe a complicated method that involves pancreatic acinar cells. According to studies on the pathophysiology of AP, damage to or disruption of pancreatic acini is the main cause of elastase, chymotrypsin, and trypsin being activated in pancreatic tissue ( Gapp et al., 2023; Gui et al., 2020). The activation of lipase, trypsin, and elastase eats away at tissue and cell membranes, causing edema, blood loss, vascular injury, and necrosis. According to epidemiological research, the local inflammatory response worsens pancreatitis by causing an increase in permeability, which reduces microcirculation, impairs local bleeding, and, in situations of severe AP, results in pancreatic necrosis. A late complication of AP or known as systemic inflammatory response syndrome (SIRS), is caused by proinflammatory mediators that are continuously activated. Pancreatic necrosis, infection, multiorgan failure, and sepsis can then occur ( Bhatia and Kumar, 2014; Patel et al., 2021).

Disorders of the gut microbiota (dysbiosis), which are related to SIRS and other diseases, are common. Gut bacteria have the ability to move to other tissues and organs in addition to the blood when the gut mucosal barrier is damaged. The severity of AP will be impacted by this. A therapeutic approach that maintains the integrity of the intestinal barrier and restores the intestinal microbiota to normal is required in order to regulate AP logically ( Swann et al., 2011; Li et al., 2020).

Animal studies revealed that probiotics may help maintain gut integrity, reducing bacterial translocation and preventing infection in AP ( Muftuoglu et al., 2006; van Minnen et al., 2007; Karen et al., 2010). Additionally, some clinical experiments have looked into the possibilities of giving critically ill patients probiotic supplements ( Sanaie et al., 2014; Rongrungruang, 2015; Zeng et al., 2016). Based on the promising findings of multiple studies, numerous clinical trials have been conducted to examine the efficacy of using prebiotics, probiotics, and synbiotics in patients with severe AP (SAP) ( Karakan et al., 2007; Oláh et al., 2007; Besselink et al., 2008; Cui et al., 2013). The research has reported valuable outcomes. However, conflicting findings are reported by the PROPATRIA study, in which probiotic supplementation has a negative impact on SAP ( Besselink et al., 2008). Several meta-analyses have been carried out to investigate the benefits of probiotics in acute pancreatitis in further detail ( Sun et al., 2009; Gou et al., 2014), and none have shown any effects on the clinical outcome of SAP patients, either favorable or negative. Tian et al.’s meta-analysis discovered that giving acute pancreatitis patients synbiotics, probiotics, and prebiotics had positive effects ( Tian et al., 2018). However, numerous additional studies with diverse findings have been published since the meta-analysis was carried out. In order to comprehensively examine the effectiveness of prebiotic, probiotic, and synbiotic therapy on clinical outcome (length of hospitalization [LoH] and complication of infection) in patients with AP, we conducted the updated systematic review and meta-analysis.

This systematic review and meta-analysis conform to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. We registered this review in PROSPERO (registration number: CRD42023427441).

The current systematic review and meta-analysis revealed two important finding in terms of clinical endpoint of acute pancreatitis patients. First, using pre-, pro-, or synbiotics reduces the LoH by 3.32 days. Second, using pre-, pro-, and synbiotics lowers the incidence of infection-related complications in people with acute pancreatitis.

Acute pancreatitis is a complex inflammatory disorder that results from the activation of pancreatic enzymes within the pancreas itself, leading to autodigestion and subsequent tissue damage. A number of things, such as gallstones, drinking alcohol, trauma, or infection, might start this process. Once activated, the pancreatic enzymes can lead to systemic consequences such multiple organ failure, sepsis, and shock, as well as severe inflammation and destruction of the pancreatic tissue. Proinflammatory cytokines, immune cell activation, mitochondrial dysfunction, and oxidative stress all play a complex role in the pathogenesis of acute pancreatitis, but the processes that cause AP to begin are still poorly understood. Additionally, recent studies have linked the gut microbiota to the onset and progression of acute pancreatitis, raising the possibility of new therapeutic approaches ( Bhatia and Kumar, 2014; Patel et al., 2021).

According to recent studies, the gut flora has a significant role in the genesis and progression of acute pancreatitis ( Patel et al., 2021). Studies have shown that alterations in the composition and functionality of the gut microbiota are associated with acute pancreatitis, including dysbiosis and increased gut barrier permeability. Dysbiosis of the gut microbiota may have a role in the pathogenesis of acute pancreatitis through mechanisms such as the translocation of gut bacteria to the pancreas, production of inflammatory mediators, and immune system modulation. The release of gut-derived endotoxins, which can trigger pro-inflammatory cytokines and worsen pancreatitis, is another potential consequence of impaired gut barrier function ( Akshintala et al., 2019; Wang et al., 2022).

In preclinical studies, it was discovered that synbiotics, probiotics, and prebiotics, among other treatments that target the gut microbiota, can lessen the severity of acute pancreatitis by reducing inflammation, improving gut barrier performance, and altering the makeup and function of the gut microbiota ( van Minnen et al., 2007; Akyol et al., 2003; Muftuoglu et al., 2006; Karen et al., 2010). Clinical research has also produced encouraging findings, with some trials showing a decrease in morbidity and death in patients with acute pancreatitis who received probiotic treatment. To completely understand the mechanisms of action and ideal dosing approaches for these therapies, more research is necessary ( Gou et al., 2014).

The PROPATRIA study’s conclusions merit careful consideration. A randomized, double-blind, placebo-controlled experiment was done as part of the PROPATRIA project to examine the effectiveness of probiotics in lowering the incidence of infections in patients with severe acute pancreatitis. Determining the occurrence of infections was the study’s main goal, and there was no discernible difference between the probiotic and placebo groups in this regard. The probiotic group did, however, have a considerably higher incidence of intestinal ischemia, according to the study ( Besselink et al., 2008). The outcome of this study discouraged the start of additional probiotics trials. However, there were a number of flaws in the PROPATRIA experiment that may have affected the validity of the results. The heterogeneity of the study cohort, which comprised patients with anticipated severe acute pancreatitis of varied etiologies and severity levels, was one of the PROPATRIA study’s primary shortcomings. Prior to randomization, 14 research participants had already experienced organ failure and six had multiorgan failure. The ability to distinguish a substantial difference in infection incidence between the probiotic and placebo groups may have been hampered by this variability. According to Bongaerts et al., the time between the onset of symptoms and the first dose of probiotics should be as short as feasible, ideally 24 hours. Within the first 24 hours, the native gut flora experienced a tremendous expansion. Additionally, the probiotic strains provided do not themselves have pathogenic potential ( Bongaerts and Severijnen, 2016). Gou et al. hypothesized that patients with severe acute pancreatitis and critical diseases who had intestinal barrier failure would experience probiotic overdoses as a result of prolonged medication duration ( Gou et al., 2014). These limitations highlight the need for further research to fully elucidate the potential benefits and risks of probiotics in the management of acute pancreatitis.

There have been a number of meta-analyses done to evaluate the effects of probiotics, prebiotics, or synbiotics on clinical outcomes in patients with acute pancreatitis. The use of pre-, pro-, or synbiotics may reduce the length of hospitalization (weighted mean difference -4.33 days; 95% CI, -7.71 to -0.95; P = 0.010), but there is no difference in septic morbidity (RR, 0.91; 95% CI, 0.73-1.13; P = 0.392), according to a recent meta-analysis of nine randomized controlled trials. However, only six research articles included in the meta-analysis for length of hospitalization and five research articles on septic morbidity were included ( Yu et al., 2021). A different meta-analysis also produced results that were comparable to those of the present study. According to data from six randomized controlled trials, pre-, pro-, and synbiotic supplementation significantly reduces the period of hospitalization for Chinese patients with severe acute pancreatitis (mean difference = -5.57, 95% CI, -8.21 to -2.93; P < 0.001) ( Tian et al., 2018). Compared to available meta-analyses, our meta-analyses provide more studies and we subgroup it according to the medication used.

Our research was also subject to several limitations. First, our research only evaluated the clinical endpoint of duration for hospitalization and risk of infection. Since the use of pre-, pro-, and synbiotics showed conflicting results, we believe that evaluating the clinical benefit in adding this intervention may provide the basis for further studies on the use pre-, pro-, and synbiotics in AP. Therefore, further studies may evaluate the biological plausibility of pre-, pro-, and synbiotics in AP. Second, our research incorporated all severities of AP. Additional research to specifically evaluate the use of pre-, pro-, and synbiotics in specific severities of AP would be beneficial.

In conclusion, adjunctive treatment of pre-, pro-, and synbiotics to standard therapy of acute pancreatitis patients provide benefits for acute pancreatitis patient. The use of those interventions may benefit for length of hospital stay and reduce complication of infection risk. Therefore, further study to evaluate the efficacy of pre-, pro-, or synbiotics are warranted with the consideration to dose and duration of intervention.