As one of the most common and severe acute abdomen diseases, intra-abdominal infections (IAIs) have become the main factor for the high mortality rate in diverse and complicated refractory disease (1). IAIs are mainly associated with abdominal traumatic surgery in the form of post-operative complications (2). The mortality rate from complicated intra-abdominal infections (CIAIs) varies between different countries and regions and ranges from 3-42% (3). In addition, the associated morbidity also exhibits an increasing trend. A previous multinational observational cohort study demonstrated that secondary peritonitis accounted for the vast majority of cases (68.4%), followed by biliary tract infection (12.2%), intra-abdominal abscess (6.9%) and pancreatic infection (6.3%) (4). IAI is a risk prognostic factor for complications of these diseases, and despite advances in treatment over the last few decades, the morbidity and mortality remain at high levels.

The definition of IAI is a general term for a class of diseases and represents a wide array of pathological conditions, including cholecystitis, pancreatitis, appendicitis, diverticulitis, and abdominal abscess and sepsis (5). Classified by its severity, IAI can be divided into two categories as follows: i) Uncomplicated intra-abdominal infection, which emerges in a single organ and is accompanied by mild symptoms; this can be treated using antibiotics therapy; and ii) CIAI, which not only affects the hollow organs, but also penetrates the pathological organs to reach the peritoneum (6), resulting in secondary peritonitis and even in severe abdominal abscess. Of note, peritonitis is typical of CIAI, and is mainly divided into primary and secondary peritonitis (Fig. 1). Moreover, CIAI can be further categorized into two types: Community CIAI that may be severe and occurring in the community, and hospital CIAI, which is also termed healthcare-acquired CIAI, usually occurring in patients who were hospitalized or who were admitted to other medical care institutions; the latter type is more common than the former (7), particularly as regards post-operative infections. IAI is a severe post-operative complication, which can lead to systemic inflammatory response syndrome, sepsis and even in multiple organ dysfunction syndrome. It induces pseudoaneurysm, sepsis and septic shock, which not only exacerbate patient suffering, but also lengthen hospital duration and increase medical costs; in addition, IAIs decreases the quality of life of patients and may even result in mortality (8).

Probiotics are live bacteria that, when consumed, modify the gut microbial flora and provide the host with health benefits (9). The use of probiotics has been examined in inflammatory bowel disease, irritable bowel syndrome and antibiotic-associated diarrhea (10-12). In the present review article, the current literature on the use of probiotic therapy in the treatment of IAIs is summarized.

The following electronic databases were used to search potentially relevant studies: PubMed (1995 to October, 2021), China National Knowledge Infrastructure (1995 to October, 2021) and Wan Fang Data (1995 to October, 2021).

The key words used included probiotics, intra-abdominal infections, intestinal barrier dysfunction (IBD), immune imbalance, mechanism, source control, antibiotics, bacterial translocation and intestinal mucosal permeability.

As is already known, there is a collection of microorganisms in nature. For the most part, this collection of microorganisms and bacteria has a negative impact on the daily life of humans. However, decades of research have revealed that bacteria, which is a subset of microorganisms that also includes viruses, fungi and other protists, plays a critical and useful role in the human body. All these microbes combine to form a chemical that some researchers have termed the microbiota. The microbiota can be found in a variety of tissues, including the mouth cavity, gastrointestinal tract, nasal cavity, and others. In particular, ~80% of the normal microbiota is concentrate in the gut (13). It has been reported that almost 1,014 bacteria are present in adult intestinal cells, which is 10-fold larger than the amount present in normal cells in the human body (14). Consequently, some researchers have even indicated that the intestinal microbiota is one of the organs in the human body (15).

The positive bacterial component is constituted by probiotics. Probiotics are microorganisms that may be of net benefit to humans when consumed. The administration of sufficient doses of probiotics, which are defined as live microorganisms, primarily modifies the balance of the intestinal microflora of the host (16). Probiotics are live microorganisms that can alter the intestinal microbial flora when ingested, and confer beneficial health effects to the host. Their use has been studied in various gastrointestinal conditions, including inflammatory bowel disease, irritable bowel syndrome and antibiotic-associated diarrhea. Metchnikff, who worked at the Pasteur Institute at the turn of the century, was the first to bring forth the hypothesis that individuals could benefit from the consumption of fermented milk (17). As a result, the World Health Organization (WHO) and the United Nations Food and Agriculture Organization (FAO) designated it as a food-grade ingredient used in dairy products that would promote the host's health. In one of his articles from 1954, Vergin (18) discussed the mechanisms thorough which antibiotics damage the healthy gut microorganisms. Since then, the general comprehension of probiotics and related applications have become increasingly thorough, and further in-depth research has been conducted.

Probiotics are currently categorized into three groups: Lactobacilli, Bifidobacteria, and Gram-positive cocci, including certain yeasts and enzymes. However, depending on the source and mode of action, they are divided into symbiotic bacteria, native bacteria and fungi (19). Lactobacilli, Bifidobacterium, butyric acid-producing bacteria, Escherichia coli (E. coli), Streptococcus thermophilus and other bacteria are all considered to be applicable to the human body on a global scale. Currently, the mechanisms of action of probiotics, such as lactic acid bacteria, Bifidobacteria and yeast, are relatively well understood, and previous research has been performed in this field. For instance, it has been demonstrated that the combined use of Lactobacillus rhamnosus GG (LGG) with conventional antibiotic therapy reduces bacterial translocation, preventing bile duct obstruction (20). Lactobacillus strains have also been shown to significantly enhance the phagocytic activity of macrophages (21). In recurrent respiratory tract infections, the abundance of Bifidobacterium has been shown to be reduced (21).

Probiotics mainly restore the balance of the flora of the body via a mechanism termed the flora-host interaction (22). A multitude of biological reactions are also involved in this process. Probiotics have been shown to function via a variety of mechanisms. For example, through competitive inhibition, they can limit the ability of pathogens to adhere to and colonize mucous membranes. Some probiotics secrete proteases which aid in the breakdown of toxins. Probiotics have also been shown to alter host immune functions by inhibiting the release of pro-inflammatory cytokines by T-cells, and some probiotic strains have been shown to inhibit mitogen-induced lymphocyte proliferation in vitro in a similar manner to dexamethasone (23). In addition, probiotic bacteria exert a potential protective effect against enteropathogens through various mechanisms, including the production of antimicrobial compounds, the reduction of pathogenic bacterial adhesion and the competition for host cell binding sites. The probiotics principle can be characterized by the following mechanisms: Immunoregulation, competitive inhibition, signal transduction and metabolic alterations are all examples of barrier function (24-27). Immunoregulation can be further divided into innate and specific immunity (25). It can also inhibit the adhesion and colonization of pathogens through competitive inhibition (28). The oral administration of probiotics can increase the number of IgA cells in the intestinal lamina propria (29). Moreover, probiotics can also induce IgA circulation and significantly increase the activity of macrophages distal to the gastrointestinal tract (30).

Approximately 230 million surgical procedures are performed worldwide each year. Some can lead to complications post-surgery, including surgical site infections, urinary tract infections, pneumonia and sepsis. Standard practice is prophylactic antibiotic treatment; however, this is complicated by the increase in antibiotic resistance. A recent network meta-analysis of 2,952 patients undergoing abdominal surgery in 31 studies revealed a beneficial effect of synbiotics on surgical site infection (62). In that meta-analysis, it was found that synbiotics (successful trials focused on Lactiplantibacillus plantarum, Lacticaseibacillus casei and Bifidobacterium breve combined with galacto-oligosaccharides) were the most effective interventions for reducing pneumonia, urinary tract infections, sepsis, hospital duration and antibiotic use, whereas they had no effect on mortality (62). It was concluded that surgeons should consider the use of synbiotics as an adjuvant treatment for the prevention of post-operative complications (54). Another meta-analysis documented similar effects (63), although it was concluded that these observations should be treated with caution due to possible publication bias. In a recent randomized controlled clinical trial, in which 55 patients who underwent liver transplants received four probiotics or polylactic acid-placebo treatments prior to the scheduled transplantation, it was shown that at 90 days following the intervention, the infection rate was significantly lower in the patients receiving the probiotics compared with the control group (5 vs. 48%, P=0.002) (64). In addition, in another randomized controlled clinical trial with 18 patients with head and neck cancer, no symbiotic effects of Lacticaseibacillus paracase, Bifidobacterium lactis, Lactobacillus acidophilus and Lactobacillus plus fructooligosaccharides were observed compared with the 18 placebo controls (65). Several clinical trials on human milk oligosaccharides (HMOs) have been registered, and HMOs may well represent a novel trend in prebiotics (66-68). Chemically defined metabolites or cell wall compounds released by probiotics may also become more important in the future (69). Probiotics may affect the gut-brain axis, with implications for patients with irritable bowel syndrome, mood disorders and anxiety (70).

In recent years, studies have demonstrated that the intestinal flora of patients with abdominal cavity infections exhibits certain dysfunctions, and the resulting intestinal microecological imbalance and the impaired IMB function may be the starting point of the inflammatory reaction of abdominal cavity infection. When the intestinal flora is unbalanced, the IMB function is impaired, and the impaired IMB function is the most important link for the occurrence of intestinal inflammatory reactions and abdominal infections. As a result, preserving the intestinal microecological balance is crucial in the treatment of abdominal infections (15,42,47,71). It has been shown that H₂O₂, bacteriocin and biosurfactant secreted by Lactobacillus can kill pathogenic microorganisms, so as to further control the inflammatory response and enhance the therapeutic effect (47).

The metabolites of probiotics play a crucial role in regulating host-disease interactions. Extracellular polysaccharide (EPSCG11) from Lactobacillus plantarum BGCG11 has been shown to alleviate inflammatory pain in rats, reducing the expression of pro-inflammatory factor, and increasing that of anti-inflammatory factors (IL-10 and IL-6), thus exerting potent anti-hyperalgesic and anti-edema effects (72). Therefore, it can be concluded that the application of probiotics for the clinical treatment of abdominal cavity infections may aid in the suppression of the inflammatory response and in relieving associated pain or discomfort.

Despite reports of microbial research in high-impact scientific journals (73-76), a broad definition of probiotics should be avoided. In the case that a probiotic is found to exert a medical effect, it should be noted that this effect is associated with specific strains or specific prebiotics, providing specific health effects in a specific patient or in a specific population. Although this statement is trivial, it is still difficult to distill these positive conclusions from the complex and sometimes contradictory research literature.

In conclusion, probiotics and their metabolites may improve the prognosis of IAIs by regulating IBF, immune regulation and dysbacteriosis. However, further large-sample, multi-center clinical trials are required to further explore the use of probiotics in the treatment of IAIs.