Authors: Ze-Long Zheng, Qing-Fan Zheng, Li-Qiang Wang, Yi Liu
Categories: Review, Bowel preparation, Colonoscopy, Microbiota, Inflammatory bowel disease, Probiotics
Source: World Journal of Gastroenterology
Authors: Ze-Long Zheng, Qing-Fan Zheng, Li-Qiang Wang, Yi Liu
The term “gut microbiota” primarily refers to the ecological community of various microorganisms in the gut, which constitutes the largest microbial community in the human body. Although adequate bowel preparation can improve the results of colonoscopy, it may interfere with the gut microbiota. Bowel preparation for colonoscopy can lead to transient changes in the gut microbiota, potentially affecting an individual’s health, especially in vulnerable populations, such as patients with inflammatory bowel disease. However, measures such as oral probiotics may ameliorate these adverse effects. We focused on the bowel preparation-induced changes in the gut microbiota and host health status, hypothesized the factors influencing these changes, and attempted to identify measures that may reduce dysbiosis, thereby providing more information for individualized bowel preparation for colonoscopy in the future.
Core Tip: Bowel preparation for colonoscopy can disrupt the gut microbiota and impact health, particularly in patients with inflammatory bowel disease. This review aims to understand these changes and minimize dysbiosis. Strategies like administration of probiotics may mitigate these effects. Moreover, the existing literature suggests that children's gut microbiota may be more resilient to the disruptions caused by bowel preparation, and that using certain agents, such as sodium picosulfate for bowel cleansing, may reduce the extent of disruption of the gut microbiota.
With the growing popularity of bacterial detection technologies such as 16S rRNA sequencing, substantial progress has been made in studies of the gut microbiota, which has been shown to be closely related to human health and disease[1]. Colonoscopy is a common method for diagnosing and treating early colorectal lesions, and its diagnostic and therapeutic potential largely depends on the quality of bowel preparation[2]. Bowel preparation mainly involves diet adjustment and the administration of bowel-cleansing agents, with polyethylene glycol (PEG) being the most frequently recommended agent at present[3,4]. However, bowel preparation can considerably alter the living environment of the gut microbiota, and its impact on the gut microbiota has become a topic of increasing concern and controversy. As probiotics and other microecological preparations can significantly improve dysbiosis of the gut microbiota caused by the use of antibiotics and other reasons[5,6], researchers have begun to consider whether probiotics can facilitate the recovery of bacterial dysbiosis after bowel preparation.
Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease mainly involving the digestive tract[7]. IBD is primarily categorized into Crohn's disease and ulcerative colitis[8]. Although the etiology of IBD is not clear, dysbiosis of the gut microbiota is one of its characteristics[9]. Colonoscopies are performed considerably more frequently in patients with IBD than in healthy people, so studying the effects of bowel preparation on the gut microbiota in patients with IBD is of particular significance.
This article will briefly introduce the common bowel-cleansing agents. Subsequently, it will focus on the changes in the gut microbiota after bowel preparation and the relationship between the related bacteria and health and disease. Additionally, the article will address the impact of bowel preparation in patients with IBD and explore the mechanism underlying these changes. Finally, it will discuss measures to improve dysbiosis.
The primary laxatives used for bowel preparation before colonoscopy include PEG, sodium picosulfate, sodium phosphate, mannitol, and Chinese herbal medicines such as senna. PEG is one of the most commonly used bowel-cleansing agents, and it is primarily used in single-dose and split-dose regimens, with split dosing being the preferred regimen[2]. As a bulk laxative, PEG can form hydrogen bonds with water molecules in the digestive tract, increase fecal water content and volume, stimulate intestinal peristalsis, and eventually cause diarrhea to achieve intestinal cleaning. PEG usually does not cause water and electrolyte disturbances in the short term[10] and has good efficacy[11], but the large solution volumes and poor taste of commonly used oral preparations are known to reduce compliance among participants[12,13]. The European Society of Gastrointestinal Endoscopy concluded that the bowel-preparation effect of magnesium citrate plus picosulfate (MCSP) was no worse than that of high-volume PEG[14]. Sodium picosulfate, on the other hand, is a stimulant laxative. Bacterial metabolites of sodium picosulfate can act on the colonic mucosa to stimulate colon peristalsis and increase fluid secretion, while magnesium salts can induce fluid retention in the colon by improving the osmotic pressure in the enteric cavity[15]. Because MCSP is a hypertonic mixture containing magnesium and can induce gastrointestinal mucosal inflammation, solutions containing MCSP should not be used in patients with hypermagnesemia, peptic ulcers, congestive heart disease, or severe renal impairment[14].
Since Mai et al[16] proposed that bowel preparation and colonoscopy may have considerable effects on the gut microbiota, researchers have conducted a series of studies on this topic (Table 1)[17-31].
The diversity of microbiota primarily reflects the number and distribution of bacterial species in a certain environment. It is mainly represented using the terms α-diversity and β-diversity. The α-diversity refers to the richness of species within a community and the number and evenness of distribution of each species. Common descriptive metrics for α-diversity include operational taxonomic units (OTUs), Chao1 index, and the abundance-based coverage estimator (ACE) index for species richness, and the Shannon index for richness and evenness. And the β-diversity is an indicator of diversity between different communities. Most of the previous studies showed a significant reduction in the α-diversity of the gut microbiota in the colonic mucosa or stool samples taken immediately after bowel preparation. This decrease was mainly characterized by a decrease of the number of OTUs, the Chao1 index, and the ACE index[17,19,26] as well as the Shannon index[17,21]. Bowel preparation is also known to affect the β-diversity of the microbiota[17,19,26]. These changes in the α- and β-diversities have been shown to persist 1 week after bowel preparation[19,24,28]. However, they mostly disappeared approximately 2 weeks after bowel preparation[28,31]. Notably, while most studies used PEG regimens for bowel cleansing, two studies that reported no considerable change in microbial diversity after bowel preparation[23,25] used sodium picosulfate as the bowel-cleansing agent.
In a study on children's gut microbiota[31], although the Shannon index decreased briefly after bowel preparation, no notable change was observed in the microbiota richness. Similarly, another study in children[23] found no considerable difference in diversity. These findings suggest that children's gut microbiota may be more “resistant” to interference from bowel preparation, although one of the studies[23] did not directly characterize age or picosulfate usage as the determining factor for this ability to resist interference.
At the phylum level, the gut microbiota is mainly composed of Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. An increase in the relative abundance of Proteobacteria after bowel preparation has been reported by many studies[20,21,26]. Shaw et al[23] further suggested that the relative abundance of Proteobacteria could be basically restored to the level before bowel preparation after 2 weeks, but Jalanka et al[20] still observed a significant increase in the relative abundance of Proteobacteria after 4 weeks. However, the participants of these two studies differed in terms of age and bowel-preparation The study by Jalanka et al[20] included adults aged 22-27 years, while Shaw et al[23] studied the effects of bowel preparation on children. These results provide additional evidence for the hypothesis that children's gut microbiota had stronger “resistance”, as speculated above. Similarly, Zou et al[31] found no considerable phylum-level changes in the major components of the microbiota after bowel preparation in children. Second, Jalanka et al[20] and Shaw et al[23] used PEG and sodium picosulfate, respectively, as laxatives. Considering the weak influence of sodium picosulfate on the diversity of the gut microbiota, as described above, its use as a bowel-cleansing agent may have relatively limited effects on the gut microbiota. However, in actual clinical application, the potential risk of IBD-like mucosal inflammatory responses that may be induced or aggravated by sodium picosulfate requires consideration[11]. Although most studies suggested that the relative abundance of Firmicutes, Bacteroidetes, and Actinobacteria will change after bowel preparation, the trends in these changes were not consistent among different studies, and the abundance usually returned to the level before bowel preparation within 2 weeks[20,23].
Drago et al[21] collected fecal samples from 10 participants at two time points. The samples collected immediately after the use of PEG bowel preparations showed a significant increase in the abundance of gamma-Proteobacteria, a significant decrease in the abundance of Lactobacilliaceae, and an increase in the abundance of Enterobacteriaceae. One month later, when the researchers re-examined stool samples from the participants, they found that the relative abundances of gamma-Proteobacteria and Lactobacillaceae had not fully recovered, and Streptococcaceae, which had not changed considerably at the first sampling, had abnormally increased. Fecal occult blood tests in these participants showed positive results, suggesting that some intestinal diseases may cause more lasting changes in the gut microbiota. Yang et al[30] compared the fecal microbiota composition of patients with gastric cancer who underwent PEG-based bowel preparation and those who did not. They also found considerably fewer Lactobacillaceae and Lactobacilli in the group that underwent bowel preparation. However, it is important to note that the participants in this study were patients undergoing surgery, and the effects of some clinical treatments may differ from those of colonoscopy alone.
At the genus level, the abundance of Faecalibacterium increased in the fecal samples of adults and children after bowel preparation with PEG and sodium picosulfate[19,23]. However, in adults, simultaneous sampling of the large intestine mucosa showed that the relative abundance of Faecalibacterium was less than that before bowel preparation[19]. Since the structure of the fecal and large intestine mucosal microbiota in adults was inconsistent, we could not confirm which group of microbiota could better reflect the impact of bowel preparation in the participants undergoing the procedure. For Veillonella, two studies[30,31] conducted in older adults and children agreed that bowel preparation using PEG significantly increased its relative abundance. More genus-level research is needed to explore whether the advantage of minimal interference with the gut microbiota when using sodium picosulfate is lost in children. For other bacterial genera, similar to the phylum-level changes, most of the changes after bowel preparation did not appear consistently, but all changes essentially disappeared within 2 weeks[20,23,25].
Due to the limited identification depth of 16S rRNA gene sequencing and other methods, many sequences are not annotated at the species level[32]. Unlike traditional microbiome research methods, metagenomics directly extracts the total DNA of all microorganisms from samples for high-throughput sequencing, allowing species-level, or even strain-level, identification of microorganisms. Zou et al[31] recently used metagenomics to comprehensively and accurately explore the effects of PEG bowel preparation on the composition of the gut microbiota. Their study showed an increase in the abundance of Escherichia coli (E. coli), Bacteroides fragilis, and Veillonella parvula (V. parvula) and a decrease in the abundance of Intestinibacter bartlettii after bowel preparation, with the abundances returning to the pre-preparation levels within 2 weeks[31]. The increase in Escherichia abundance after bowel preparation in this study and the increase in Enterobacteriaceae reported by Drago et al[21] imply that bowel preparation can increase the abundance of E. coli at the family, genus, and species levels. Notably, the study by Zou et al[31] was conducted in minors with an average age of approximately 10 years, so the applicability of their findings to other populations needs to be evaluated using metagenomics and other deep sequencing technologies.
As mentioned above, bowel preparation was followed by an increase in the abundance of Proteobacteria, Streptococcaceae, Veillonella, and E. coli as well as a decrease in the abundance of Faecalibacterium and Lactobacillaceae. Here, we discuss these bacteria in terms of their categorization as human pathobionts and beneficial microbes. Pathobionts are commensal microbes widely found in the body of healthy people, but they can be closely related to human diseases in some scenarios. As the name suggests, beneficial microbes refer to microorganisms that are beneficial to human health in most scenarios. Notably, the classification of pathobionts and beneficial microbes is not absolute, and very few bacteria are only beneficial or harmful to human health. Moreover, some of the results described in this section are based on observational data and cannot directly indicate whether dysbiosis of the microbiota is a cause or consequence of the relevant disease.
Proteobacteria exhibit varying morphologies and metabolic types, so their name is derived from Proteus, the Greek god with the ability to change appearance. Unlike the obligate anaerobes that dominate the human gut microbiota, most members of the intestinal Proteobacteria are facultative anaerobes[33]. Under normal physiological conditions, the intestinal lumen maintains an anaerobic state, and the trace amounts of oxygen entering the intestinal lumen are also consumed by facultative anaerobes such as Proteobacteria. High oxygen levels in the intestine inhibit the growth of obligate anaerobes and promote the growth of Proteobacteria, which can use oxygen for metabolism[34]. Previous studies have shown that both antibiotics and intestinal inflammation can lead to an increase in intestinal oxygen content and thus promote the proliferation of Proteobacteria[35]. Bowel preparation also disrupts the anaerobic environment in the intestinal lumen, which may partly explain the increase in Proteobacteria after bowel preparation. This change in the abundance of Proteobacteria is a marker of dysbiosis of the gut microbiota[33]. It is also associated with IBD[36-38], irritable bowel syndrome[39], colorectal cancer[40,41], obesity[42], malnutrition[43], and other diseases[44]. Several studies have suggested that the abundance of Proteobacteria is higher in the gut of patients with diabetes[45,46]. However, recent studies of placental and neonatal meconium from patients with gestational diabetes mellitus (GDM) have shown that the relative abundance of Proteobacteria in these patients was abnormally lower than that in controls[47,48], while no considerable change was observed in the abundance of Proteobacteria in the intestinal tract of patients with GDM[49].
The abundance of Streptococcaceae is positively correlated with the production of fecal proteases[21]. Jalanka et al[20] previously reported an increase in fecal protease levels after bowel preparation; however, their study did not identify considerble changes in the abundance of Streptococcus. The authors speculated that the increase in fecal protease levels may be related to a decrease in the abundance of protease-degrading bacteria. Proteases are a diverse group of evolutionarily conserved enzymes that cut peptide bonds to hydrolyze proteins. Feces contain a variety of proteases produced by the host and the microbiota, and these enzymes play an important role in maintaining intestinal homeostasis under physiological conditions[50]. However, excessive production of proteases can damage the integrity of the intestinal epithelium[51] and promote inflammatory responses[52]. Increased levels of host- or bacteria-derived proteases have been reported in IBD[53-56], irritable bowel syndrome[57,58], and other gastrointestinal diseases. Notably, Drago et al[21] observed an increase in the abundance of Streptococcus one month after bowel preparation, while Jalanka et al[20] reported that the increase in protease levels was transient and that protease inhibitors in the intestine could control the damage caused by proteases[50]. Therefore, the significance of the excess fecal protease levels after bowel preparation for human health and disease remains to be further studied.
Veillonella is a gram-negative diplococcus that widely exists in the human oral cavity, intestinal tract, and urogenital tract[59]. It was first isolated from the infected human appendix in 1898 by Veillon and Zuber, and was later re-described by Prevot and categorized under the genus Veillonella[60]. V. parvula is the earliest discovered and most important species of Veillonella. The oral cavity serves as an endogenous reservoir of intestinal microorganisms, and oral microorganisms often spread to and colonize the gut[61]. As a major group of oral microbiota, Veillonella migrates into the intestine during physiological processes such as saliva swallowing[61,62], which may be one of the reasons for the abnormal increase in Veillonella after bowel preparation. In addition, if bowel preparation can indeed increase the abundance of Streptococcus as mentioned above, the resultant increase in the production of Streptococcus metabolites (such as lactic acid) can also provide a carbon source and energy for the growth and reproduction of Veillonella[63]. Veillonella has dual effects on human health and disease. Veillonella, as an important part of the biofilm in multiple parts of the human body, holds great significance in maintaining the stability of the normal human microbiota. The ability of Veillonella to utilize lactic acid as a carbon and energy source has attracted particular attention since lactic acid consumption by Veillonella may help prevent effect dental caries[64] (the overall effect of Veillonella on dental caries is still controversial), and the conversion of lactic acid to propionic acid in the intestine by Veillonella can significantly improve exercise endurance[65]. On the other hand, an increase in the abundance of Veillonella is also closely related to diseases such as IBD[66-68]. The lipopolysaccharides of Veillonella may play an important role in the occurrence and development of diseases[60,69,70]. In patients with IBD, increased levels of nitrate due to inflammation can promote the growth and colonization of Veillonella in the intestine through the narGHJI operon[62]. Therefore, post-colonoscopy changes in the abundance of Veillonella should receive attention in patients diagnosed with IBD.
E. coli is an important member of the genus Escherichia in Enterobacteriaceae. E. coli in humans can be roughly divided into four Non-pathogenic, diarrheagenic, extra-intestinal, and mixed pathogenic[71]. Non-pathogenic E. coli are an important part of the normal gut microbiota, while pathogenic E. coli can cause a variety of intra- and extra-intestinal diseases[72-74]. Different types of E. coli have different pathogenic mechanisms, mainly relying on enterotoxins, adhesins and pili, and can also play a pathogenic role by producing proteases[50].
Many bacteria belonging to Lactobacillaceae are beneficial to human health and widely used as probiotics, especially Lactobacillus, the largest genus in Lactobacilliaceae. The probiotic effect of Lactobacillus is achieved through the interaction of its surface-active molecules, which mainly include bacterial polysaccharides, teichoic acid, and various bacterial proteins, with the human body[75]. In addition, Lactobacillus metabolites and secretions play important roles in maintaining body health[76]. The relative abundance of gut Lactobacillus is negatively correlated with the occurrence of various digestive tract diseases, including IBD[77,78]. A recent study also showed that a reduction in the abundance of Lactobacillus in the gut may be related to dysbiosis of systemic glucose metabolism[79].
As one of the microorganisms with the greatest potential to become a next-generation probiotic[80], Faecalibacterium can help maintain host health and improve resistance to diseases. Most members of Faecalibacterium are strictly anaerobic bacteria[81], and their growth is inhibited in oxygen-rich environments, which may partly explain the decrease in Faecalibacterium after bowel preparation. Faecalibacterium can metabolize cellulose in the intestinal tract into butyrate[82], which can serve as a source of energy, regulate metabolism, enhance intestinal barrier function, and show anti-inflammatory and anti-tumor activities[83-85]. A number of studies have described reduced abundance of Faecalibacterium in IBD[86-88]. One possible mechanism is that Faecalibacterium can regulate the differentiation and proliferation of regulatory T cells through various pathways such as butyrate production, thereby reducing inflammatory response[89-91].
Shobar et al[22] studied the changes in the gut microbiota of patients with IBD and a healthy control group after bowel preparation. They found that the proportion of common OTUs between sigmoid mucosal and fecal samples in patients with IBD increased after bowel preparation, while the Unifrac distance decreased. A higher number of shared OTUs and a decrease in the Unifrac distance often indicate greater similarity in microbial composition between two samples. The researchers hypothesized that bowel preparation may shift some of the bacteria in the stool to the intestinal mucosa, increasing the inflammatory response of the mucosa. Simultaneously, the study also showed that the Shannon index of the mucosal microbiota, which characterizes α-diversity, decreased only in patients with IBD and did not show such changes in healthy controls. The reduction in diversity is an important factor causing instability of the microbiota[92,93], and is also one of the characteristic changes of the gut microbiota in IBD[94]. However, in other studies on the fecal microbiota in healthy people, the Shannon index also decreased after bowel preparation. This may have occurred because mucosa-associated microbiota can better characterize the gut microbiota of IBD patients than fecal microbiota[95]. This variation may also be attributed to differences in the characteristics of the participants enrolled in various studies, specimen-collection methods, dietary interventions, and other factors.
In a study of non-IBD patients, Gorkiewicz et al[19] and Jalanka et al[20] also found similarities between the changes in the gut microbiota in non-IBD patients after bowel preparation and patients with IBD. “The oxygen hypothesis” proposes that the shift in bacterial communities from obligate to facultative anaerobes as a result of destruction of the intestinal anaerobic environment is an important factor leading to the occurrence of IBD[96]. As a chronic inflammatory response in the intestine, IBD can lead to high levels of oxidative stress, change the levels of oxygen and reactive oxygen species (ROS) in the intestinal lumen, and ultimately lead to dysbiosis of the microbiota[97,98]. Bowel preparation also increases intestinal oxygen content[99], which may be one of the reasons why bowel preparation and IBD can have similar effects on the microbiota. The close relationship between the changes in pathobionts and beneficial microbes after bowel preparation and IBD has also been discussed above. In summary, we speculate that bowel preparation may aggravate IBD in some cases, although a causal relationship between changes in the gut microbiota and IBD has not been established[100].
Bowel preparation may change the gut microbiota by clearing intestinal mucus, flushing the bacteria themselves and the nutrients required for their metabolism, and destroying the anaerobic environment in the intestine[99]. Future studies should attempt to further verify whether changes in the intestinal oxygen level are a key pathway underlying this process.
The gut microbiota is a highly complex microbial community, and its changes are influenced by many factors[101]. Currently, there is insufficient evidence to identify the predominant factors influencing the recovery of the gut microbiota after disruption. We speculate that the following factors may play a (1) Microbiota The gut microbiota is a complex ecosystem with stability, resistance, and resilience, and it can be maintained at or restored to a stable state through various mechanisms such as competition and cooperation among microorganisms as well as interactions with the host[102-104]; (2) The oral-gut microbiome axis of the host. The oral cavity is the second-largest reservoir of bacteria in the human body[105], and its microbiota can migrate with saliva and food and colonize the colon, especially when the colonic epithelium is in an inflammatory or damaged state[106-108]. In addition to direct translocation of oral bacteria, the T cells activated by oral inflammation have been also reported to enter the gut[109]. This "flow" of bacterial and immune cells is not random, and is regulated by the oral-gut barrier. The oral-gut barrier is mainly composed of gastric acid in the stomach[110,111] and bile acid secreted into the small intestine[112], and damage to this barrier can accelerate the flow of microorganisms from the oral cavity to the gut. Proton pump inhibitors have been shown to induce or aggravate intestinal inflammation by damaging the barrier[113,114]. However, the influence of large amounts of fluids taken during bowel preparation on the oral-gut barrier and how this potential damage can be restored needs to be studied further; (3) The host immune system. The gut microbiota shows complex and close interactions with the immune system[115]. Intestinal epithelial cells and immune cells work together to precisely control the gut microbiota[116], and the immune system generally tends to mold gut bacteria into a highly diverse community dominated by obligate anaerobes[117]. In particular, intestinal mucus is involved in the composition of the intestinal barrier by selectively segregating bacteria from the immune system[118], and the abnormal immune response triggered by the destruction of the intestinal barrier may be an important link in the occurrence of IBD[119]. The use of PEG in intestinal preparation has been reported to lead to the loss of intestinal superficial mucus[120]; (4) Host living habits. Different diets can shape different gut microbiota[121]. For example, consumption of foods rich in dietary fiber will significantly increase the diversity of the gut microbiota and orient the composition and metabolism of the gut microbiota toward a healthier direction[122,123]. Vaccaro et al[124] speculated that lack of sleep also disrupts the balance of the gut microbiota through the accumulation of ROS. Recent studies have even observed that large temperature differences can change the composition of the gut microbiota[125]; and (5) Mitochondria of host cells. The mitochondria of intestinal epithelial cells and the gut microbiota interact through complex mechanisms. Bacterial metabolites, bioactive substances produced by bacteria, and bacterial components can affect the function, microstructure, and dynamics of mitochondria; conversely, changes in mitochondria can also reshape the gut microbiota[126,127]. In addition to controlling ROS production as mentioned in (4), mitochondria can also influence gut microbiota by altering the oxygen consumption of metabolic processes. Butyrate, a bacterial metabolite, can activate peroxisome proliferator-activated receptor γ in colonic epithelial cells to mediate the transition of cell metabolism to β-oxidation and oxidative phosphorylation, maintaining the oxygen-consuming metabolism of cells and thus ensuring the anaerobic environment of the intestinal tract[117,128]. This is of great significance for maintaining the dominance of obligate anaerobic bacteria in the gut microbiota[129]. In addition, interactions between the gut microbiota and mitochondria are not limited to intestinal epithelial cells; researchers have identified communication between the gut microbiota and mitochondria in cells of the liver[130] and nervous system[131,132]. Notably, the factors discussed above do not work in isolation; for example, the diet, microbiome, and immune system function as a complex network[133].
The effects of bowel preparation on the gut microbiota are short-lived in most healthy people. As mentioned above, most of the indicators return to the state before bowel preparation within 2 weeks. Sommer et al[134] referred to this ability of the gut microbiota to return to equilibrium after external perturbations as “the resilience phenomenon”. Disturbances above a certain threshold can also cause the gut microbiota to change to another state for a long time, but no definition for this threshold has received consensus to date[135].
In the study by Wang et al[28], elderly Chinese adults who underwent colonoscopy using PEG for bowel preparation subsequently received Saccharomyces boulardii or Bacillus subtilis combined with Enterococcus faecium. This probiotic treatment significantly increased the richness and diversity of the gut microbiota. However, their study did not elaborate the effects of probiotics on the composition of the microbiota. Deng et al[26] found that administration of tablets containing a combination of Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus cereus significantly reduced the relative abundance of Proteobacteria and increased the relative phylum-level abundance of Bacteroidetes. At the genus level, the probiotics significantly reduced the abundance of pathogenic Acinetobacter and Streptococcus, and increased the relative abundance of beneficial bacteria.
A randomized controlled trial by D'Souza et al[136] explored the effect of Lactobacillus acidophilus (L. acidophilus) and Bifidobacterium lactis (B. lactis) on abdominal symptoms after colonoscopy with air insufflation. Their findings showed a significant improvement in abdominal pain symptoms after the administration of probiotics. Wang et al[28] also reported that probiotics can significantly improve the incidence of abdominal pain, abdominal distension, and diarrhea after colonoscopy. Although their study did not clearly identify the type of gas injected during colonoscopy, most colonoscopy examinations in China use air insufflation. However, both bowel preparation before colonoscopy and air insufflation during colonoscopy can alter the gut microbiota. In another study that also used L. acidophilus and B. lactis[137], the researchers used carbon dioxide insufflation for colonoscopy and found that probiotics had a limited effect on abdominal symptoms after colonoscopy. In summary, while the use of probiotics can improve abdominal discomfort after colonoscopy, these symptoms may be attributable to the bacterial dysbiosis caused by air insufflation rather than bowel preparation.
The current strategy for bacterial recovery after colonoscopy is essentially limited to the use of probiotics, but many directions of research on promoting gut microbiota recovery after antibiotic treatment are under investigation. The use of antibiotics can also lead to a decrease in the gut microbiota diversity and an increase in facultative anaerobic bacteria[101]. Fecal microbiota transplantation[138,139] and dietary regulation[140] have been found to significantly improve gut microbiota after antibiotic use, so further studies are needed to verify whether these methods also work after colonoscopy. Measures to regulate gut microbiota from the perspective of host cell mitochondria, the immune system, and the oral-gut microbiome axis are still in the exploration stage. Recent findings showing that nicotinamide mononucleotide supplementation can reverse mitochondrial DNA mutations in intestinal cells[141] may be enlightening in this context.
Bowel preparation before colonoscopy usually causes the gut microbiota to temporarily shift to an unhealthy state, which is mainly characterized by reductions in microbiota diversity and the populations of beneficial bacteria and an expansion in the populations of harmful bacteria. These changes mostly resolve within 2 weeks due to the combined action of various potential factors. Children’s gut microbiota appears to be more stable, at least in terms of the diversity and composition of the gut microbiota at the phylum level. Bowel preparation may worsen the condition of patients with IBD, highlighting the need to minimize unnecessary colonoscopies in this population. In addition, the use of sodium picosulfate as a bowel-cleansing agent and the application of probiotics may reduce the interfering effects of colonoscopy on the gut microbiota. Some of the studies cited in this review had the following issues that require (1) The influence of confounding factors, such as differences in the participants’ pre-existing gut microbiota types - enterotypes, cannot be ruled out. Different enterotypes show varying levels of resistance to external perturbations, which has not received sufficient attention in most studies. Although Chen et al[24] initially studied enterotype classification, they focused only on overweight men; (2) The limitations of sequencing methods were not adequately addressed. 16S rRNA gene sequencing and other methods lack sufficient depth to accurately present species-level changes in the gut microbiota. The use of metagenomics for gut microbiota analysis is also associated with problems such as susceptibility to host DNA interference; and (3) The conflicting results among different studies remain unexplained. While many studies observed a reduction in the α diversity of fecal microbiota sampled immediately after bowel preparation, Nagata et al[25] found no considerable change in the Shannon index, and Feng et al[48] even detected an increase in α diversity. Moreover, the composition of certain gut microbiota also varied across studies. Considering the current status of research on this topic, future studies may need to work on the following (1) Strict screening or control of the characteristics of the enrolled population, diet during the experiment, fecal collection method, and gas injection during colonoscopy as well as assessments on the basis of different groups of factors such as enterotypes; (2) Precise analysis of the composition and function of gut microbiota through metagenomics combined with 16S rRNA gene sequencing and other techniques; (3) Establishment of controlled trials to further validate the benefits of young age and picosulfate in preventing bowel-preparation interference; (4) Determination of the threshold for changes in the gut microbiota caused by external disturbances, such as the frequency of colonoscopies, for bowel preparation in patients with IBD; and (5) Identification of the most appropriate probiotic species and other effective strategies to promote the recovery of intestinal flora in patients with IBD.