Alteration in gut microbiota after colonoscopy: proposed mechanisms and the role of probiotic interventions

Alteration in gut microbiota after colonoscopy

Article information

Clin Endosc. 2024;.ce.2024.147

Publication date (electronic) : 2024 September 2

doi : https://doi.org/10.5946/ce.2024.147

Hyeong Ho Jo ¹^,^*

, Moon Young Lee ²^,³^,^*

, Se Eun Ha ⁴

, Dong Han Yeom ⁵

, Yong Sung Kim^,²^,⁶

¹Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea

²Digestive Disease Research Institute, Wonkwang University College of Medicine, Iksan, Korea

³Department of Physiology, Wonkwang University School of Medicine, Iksan, Korea

⁴Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA

⁵Department of Gastroenterology, Wonkwang University School of Medicine, Iksan, Korea

⁶Good Breath Clinic, Gunpo, Korea

Correspondence: Yong Sung Kim Digestive Disease Research Institute, Wonkwang University School of Medicine, 460 Iksan-daero, Iksan 54538, Korea E-mail: wms89@hanmail.net

*Hyeong Ho Jo and Moon Young Lee contributed equally to this work.

Received 2024 June 6; Revised 2024 July 10; Accepted 2024 July 13.

Abstract

Colonoscopy, a widely used procedure for diagnosing and treating colonic diseases, induces transient gastrointestinal symptoms and alterations in the gut microbiota. This review comprehensively examines the evidence on alterations in the gut microbiota following colonoscopy and their possible mechanisms. Factors such as rapid colonic evacuation, increased osmolality, and mucus thinning caused by bowel preparation and exposure to oxygen during the procedure contribute to these alterations. Typically, the alterations revert to the baseline within a short time. However, their long-term implications remain unclear, necessitating further investigation. Split-dose bowel preparation and CO₂ insufflation during the procedure result in fewer alterations in the gut microbiota. Probiotic administration immediately after colonoscopy shows promise in reducing alterations and gastrointestinal symptoms. However, the widespread use of probiotics remains controversial due to the transient nature of both the symptoms and gut microbial alterations following a colonoscopy. Probiotics may offer greater benefits to individuals with preexisting gastrointestinal symptoms. Thus, probiotic administration may be a viable option for selected patients.

Keywords: Colonoscopy; Dysbiosis; Microbiota; Probiotics

INTRODUCTION

In recent decades, there has been a surge in research on the influence of the gut microbiota on the host’s health.1 The gut microbiota is a diverse array of microbial communities of bacteria, protozoa, fungi, viruses, and archaea, forming a dynamic ecosystem within the human body with their metabolic activities.2 The number of gut microbiota cells nearly matches that of human cells. Even more impressively, their genetic repertoire is more than 100 times greater than that of the human body. This enables them to perform functions beyond the human body's capacity and participate in many physiologic processes crucial for maintaining the host’s health.1 Imbalance in the composition of the gut microbiota, known as dysbiosis, has been implicated in various conditions, including metabolic, gastrointestinal, neoplastic, and neuropsychiatric disorders.1,3 Although there is no consensus on a clear definition of dysbiosis, maintaining gastrointestinal microbial balance is essential for preventing or managing these disorders. Dysbiosis may manifest even without overt pathology and can become associated with disease when it persists beyond a certain threshold over an extended period.

Colonoscopy is commonly used to screen and monitor various colonic diseases. However, gastrointestinal symptoms are frequently reported after colonoscopy. One study found that 40% to 45% of individuals experienced a range of symptoms, including abdominal bloating, abdominal pain, and dyspepsia, within 7 to 30 days after colonoscopy.4,5 Gastrointestinal symptoms were more common in women and patients with longer procedure times and inflammatory bowel disease.4,5 Underlying dysbiosis may also contribute to the development of post-colonoscopy symptoms. In a large cohort study of individuals undergoing screening colonoscopy, those exposed to antibiotics around the time of the procedure showed slightly higher rates of surrogate symptoms than matched controls who did not use antibiotics.6

Colonoscopy is a typical cause of inducing transient, non-pathological alterations of the gut microbiota. However, it is unclear whether these alterations are related to post-colonoscopy symptoms or to the aggravation of a preexisting disease.7 This review examines the evidence on gut microbiota alterations after colonoscopy and the underlying mechanisms. Moreover, it summarizes the current knowledge of the role of probiotic administration in managing gastrointestinal symptoms and the alterations in the gut microbiota after colonoscopy.

We conducted a thorough literature search in the PubMed database in this review. For studies investigating alterations in gut microbiota after colonoscopy, we used the following search terms: (colonoscopy AND (microbiota OR microbiome) AND (dysbiosis OR effect OR alter OR change)). To identify studies examining the effects of probiotic use before and after colonoscopy, we used the search terms: (colonoscopy AND (probiotics OR probiotic)). We did not restrict publication year, language, or study design. Studies were screened for relevance based on titles and abstracts, and duplicates were removed. Additionally, we reviewed the reference lists of the selected articles to identify further relevant studies.

ALTERATIONS OF GUT MICROBIOTA AFTER COLONOSCOPY

The bowel preparation performed before a colonoscopy to achieve the complete evacuation of the colonic content leads to a temporary yet significant alteration in the gut microbiota compositions. Bowel preparation agents are broadly categorized into polyethylene glycol (PEG) formulations, osmotically active saline solutions, and combination preparations. Since their introduction in the 1980s, PEG electrolyte solutions have been the most commonly used agents for colonoscopy.8 They are considered a safe preparation method and can be used relatively safely even in patients at risk of electrolyte imbalance due to kidney, liver, or heart disease. Consequently, most studies on alterations in the colonic microbiota after colonoscopy have focused on PEG-based bowel preparation agents.

In 2006, Mai et al.9 conducted a pioneering study involving five healthy adults to examine the effects of colonoscopy on the gut microbiota using denaturing gradient gel electrophoresis. Their findings showed a disturbance in the gut microbiota composition after colonoscopy. Subsequently, several other studies have explored gut microbiota alterations after colonoscopy.9-23 However, the findings have been inconsistent due to the small numbers and heterogeneity of participants, variations in the bowel preparation agents used, and differences in the methods and depths used to detect changes in the gut microbiota. Details on each of these studies are provided in Table 1.9-23 In general, colonoscopy has been found to reduce the total number and α-diversity of gut microorganisms. At the phylum level, a decreased abundance of Firmicutes and Bacteroidetes, an increased abundance of Proteobacteria, and a decreased Firmicutes/Bacteroidetes ratio have been reported in healthy subjects. Notably, an increase in Proteobacteria levels has been consistently observed across studies.11,13,15,18 At lower taxonomic levels, an increase in opportunistic pathogens (e.g., Pseudomonas and Acrobacter) and a decrease in beneficial microbiota (e.g., Clostridia and Lactobacillaceae) have been reported. However, these findings have been inconsistent, with some studies reporting no significant changes in the gut microbiota composition after colonoscopy.

Table 1.

Studies associated with the effects of bowel preparation and colonoscopy on gut microbiota

The gastrointestinal microbiota is dominated by the phyla Firmicutes and Bacteroidetes, with a lower prevalence of Proteobacteria, Actinobacteria, Verrucomicrobia, and Saccharibacteria (formerly known as TM7).24 While most gastrointestinal microorganisms are obligate anaerobes, Proteobacteria are facultative anaerobes.25 Dysbiosis in the colon is commonly associated with an increased abundance of Proteobacteria, which is observed in individuals who undergo antibiotic therapy, consume a high-fat Western-style diet, or have conditions such as inflammatory bowel disease, colorectal cancer, irritable bowel syndrome, or necrotizing enterocolitis.25,26 Although the abundance of Proteobacteria increases after colonoscopy, it remains unclear whether this alteration should definitively be considered dysbiosis, as observed in other disorders, primarily due to its transient nature. Nevertheless, it may contribute to the emergence of post-colonoscopy gastrointestinal symptoms or exacerbate preexisting dysbiosis. While this relationship remains unclear, one study showed that individuals experiencing post-colonoscopy symptoms exhibited lower baseline α-diversity than individuals who did not have such symptoms.18

Most studies have reported that the gut microbiota composition returns to the baseline within 2 to 6 weeks after colonoscopy, suggesting the resilience of the gut microbiota. However, baseline gut microbiota status, predisposing factors, such as inflammatory bowel disease, and bowel preparation methods may affect the extent and reversal of changes after colonoscopy. The gut microbiota recovery rate after colonoscopy has been found to depend on the PEG administration method, with split-dose PEG administration having a less disturbing effect and resulting in better microbial recovery than a single dose.13 The changes in the gut microbiota after colonoscopy have been shown to differ between patients with inflammatory bowel disease and healthy individuals in terms of α- and β-diversity.14,19,23 Furthermore, a complete recovery may not occur in some populations. For example, in a study of overweight subjects, Prevotella-dominant gut microbiota was more susceptible to dysbiosis after colonoscopy than Bacteroides-dominant microbiota.17

POSSIBLE MECHANISMS OF GUT MICROBIOTA ALTERATIONS AFTER COLONOSCOPY

Several mechanisms have been proposed to explain the temporary alterations observed in the gut microbiota after colonoscopy. However, most have yet to be definitively proven (Fig. 1). These mechanisms are described in the following subsections.

Fig. 1.

Postulated mechanisms of gut microbiota alterations after colonoscopy. Bowel preparation using osmotic laxatives, such as polyethylene glycol, facilitates the rapid evacuation of colonic contents, including fecal matter and nutrients, while increasing osmolality within the gastrointestinal tract. This process induces significant changes in the gut microbiota. It precipitates mucus depletion and alterations in epithelial cells, leading to modifications in submucosal immune responses, thereby further influencing the gut microbiota composition. Moreover, exposure to oxygen during the colonoscopy exacerbates the disruption of gut microbiota induced by bowel preparation. These combined effects usually result in an increased relative abundance of Proteobacteria. If anaerobic bacteria and fiber decrease in the colonic lumen after colonoscopy, butyrate production may be reduced, causing colonic epithelial cells to consume less oxygen. This may result in increased levels of oxygen released from the epithelial surface, further inducing a shift in the microbial community from obligate to facultative anaerobic bacteria. While individuals with a healthy gut microbiota typically return to the baseline shortly after colonoscopy, individuals with underlying gastrointestinal disorders, such as inflammatory bowel disorders or irritable bowel syndrome with antibiotic exposure, and those with baseline dysbiosis may experience sustained alterations in the gut microbiota. Split-dose bowel preparation and CO₂ insufflation during the procedure have been found to be less disruptive to the gut microbiota. Furthermore, administering probiotics immediately after colonoscopy may reduce post-procedural gastrointestinal symptoms and microbiota alterations, particularly in individuals with preexisting gastrointestinal symptoms.

Rapid evacuation of luminal content through bowel preparation

The rapid increase in bowel movements induced by bowel preparation flushes out fecal material along with microorganisms that cannot adhere to the intestinal mucosa. Moreover, the reduced availability of nutrients that are essential for bacterial metabolism, including dietary fiber and fermentable carbohydrates, contributes to the decrease of the gut microbiota. These factors collectively induce a significant change in the gut microbiota composition, characterized by an increased abundance of Proteobacteria.7 However, this compositional change is not exclusive to colonoscopy. Studies on acute infectious diarrhea, primarily conducted in pediatric populations, have reported comparable changes in the gut microbiota composition similar to those seen after colonoscopy, including a decrease in α-diversity, an increased abundance of Streptococcus, Escherichia, and Bacteroides, and a decreased abundance of Roseburia, Faecalibacterium, Blautia, Prevotella, and Lactobacillus.27-30 Moreover, the alterations in the gut microbiota reported in noninvasive viral infectious diarrhea, such as Rotavirus diarrhea, may resemble those induced by bowel preparation for colonoscopy, with an increased abundance of Proteobacteria, especially the class Gammaproteobacteria.28 Thus, regardless of the cause, the rapid evacuation of colonic contents through osmotic or secretory diarrhea may lead to a decrease in the major phyla Firmicutes and Bacteroidetes, potentially allowing Proteobacteria to occupy the niche as an epiphenomenon of the wash-out effect.11 On the other hand, no increase in Proteobacteria has been observed in patients with diarrhea caused by bile acids after cholecystectomy, suggesting a different effect of bile acid diarrhea on the gut microbiota.31,32

Direct effect of osmotic laxatives on the host’s intestinal environments, mucus layer, and epithelium

Unlike in the case of infectious diarrhea, it is necessary to consider both the direct effects of bowel preparation agents and the indirect consequences of changes in the host’s immune function in the case of colonoscopy-induced gut microbiota alterations. The growth of the gut microbiota is influenced by the host's physiological and immunological state and environmental factors within the gut lumen.33 The growth rate of microorganisms decreases when environmental osmolality increases, regardless of the type of osmolyte, suggesting that the high osmolality of the preparation agents may directly affect the gut microbiota.34 The heightened osmolality induced by PEG leads to a decreased bacterial cell volume due to passive water excretion, which occurs on a timescale of seconds. In a humanized microbiota mouse model study, chronic PEG administration decreased Verrucomicrobiae and increased Gammaproteobacteria. Moreover, there was a decrease in Muribaculaceae (previously known as S24-7) and an increase in Bacteroidaceae.34

Furthermore, during diarrhea, there is a significant decrease in mucus thickness, resulting in decreased Akkermansia, a microorganism specializing in intestinal mucus consumption. Despite the depletion of the mucus layer at the epithelial interface, the epithelium remains intact, except for a reversible flattening of epithelial nuclei due to the high osmolality of PEG.34 Unlike senna and sodium phosphate, which can cause significant mucosal damage, PEG does not cause significant histological changes, such as a reduction in goblet cells in the colonic mucosa.35,36 However, some studies have reported superficial mucus loss, epithelial cell loss, edema in the lamina propria, lymphocyte infiltration, and polymorphonuclear cell infiltration associated with PEG administration.37 These alterations in the mucus and epithelial cell layers, which are critical for maintaining mucosal immune function, negatively impact the gut microbiota and the host.

Disruption of the anaerobic ecosystem due to exposure to oxygen

The alteration in the gut microbiota after colonoscopy may be attributed not only to the rapid evacuation and osmotic effects caused by bowel preparation but also to exposure to oxygen, as suggested by the increased abundance of Proteobacteria after colonoscopy. Unlike most microbes in the colon, which are strictly anaerobic, Proteobacteria often have facultative anaerobic characteristics, which enable them to tolerate various oxygenic conditions.25 It has been suggested that oxygen conveyed into the lumen during bowel preparation disrupts the anaerobic ecosystem of the colon.7 However, the evidence supporting this notion remains insufficient. Rather, it is plausible that air insufflated during colonoscopy plays a significant role in exposing mucosal-associated microbes to oxygen, thereby exacerbating the dysbiosis triggered by bowel preparation.

Another possible cause is the diffusion of oxygen into the colonic lumen due to alterations in the function of colonic epithelial cells. It is now recognized that colonic epithelial cells play a central role in maintaining homeostasis by modulating the colonic microbiota. Obligate anaerobic bacteria produce butyrate by fermenting fiber, thereby maintaining the epithelium in a metabolic state characterized by high oxygen consumption.26,38 This, in turn, maintains epithelial hypoxia (<1% oxygen), limiting oxygen diffusion into the colonic lumen.26 If anaerobic bacteria and fiber decrease in the colonic lumen after colonoscopy, butyrate production can be reduced, causing colonic epithelial cells to consume less oxygen. This may result in increased levels of oxygen and nitrate released from the epithelial surface, further inducing a shift from obligate to facultative anaerobic bacteria in the microbial community. However, it remains unclear whether such phenomena also occur in short-term alterations of the gut microbiota after colonoscopy and to what extent they may impact if they do.

CO₂ insufflation may cause less disturbance to the colonic microbiota than room air. A small randomized controlled trial involving 10 healthy subjects demonstrated that CO₂ insufflation promoted gut microbiota homeostasis during colonoscopy.39 Species richness after colonoscopy decreased more slowly and recovered more quickly in the CO₂ group than in the air group. CO₂ insufflation increased the relative abundance of some anaerobic Bacteroides species (e.g., Bacteroides caccae), Subdoligranulum, and Lachnospiraceae, whereas air insufflation increased the relative abundance of Escherichia coli, Ruminococcus torques, and Ruminococcus gnavus.39 However, there were no significant differences in the gut microbiota composition within or between the groups at 1, 3, 7, 14, and 28 days after colonoscopy. Colonoscopy with room air may worsen symptoms slightly in patients with ulcerative colitis, with most patients experiencing a deterioration by the first week and a significant improvement by the fourth week.40 In a randomized controlled trial comparing CO₂ and room air insufflation during colonoscopy in patients with a partial Mayo score of 1 or 2, the rate of clinical relapse at eight weeks after colonoscopy was significantly lower in the CO₂ group than in the room air group.41 This suggests that CO₂ is more beneficial in terms of preventing mucosal inflammation by causing less disturbance to gut mucosa-associated microbes during colonoscopy. In another randomized controlled trial, patients with irritable bowel syndrome exhibited more severe post-colonoscopy symptoms than the controls. CO₂ insufflation reduced post-colonoscopy symptoms in both groups compared to room air insufflation, and the effect was higher in patients with irritable bowel syndrome than in the controls.42

COULD PROBIOTICS HELP RESTORE COLONOSCOPY-INDUCED ALTERATIONS IN THE GUT MICROBIOTA?

Several randomized placebo-controlled trials have explored the efficacy of various probiotic strains in alleviating gastrointestinal symptoms following colonoscopy (Table 2).42-49 In one study, patients with constipation who received probiotics two weeks before the procedure experienced significantly lower rates of vomiting and bloating than those who received a placebo. However, this effect was not observed in individuals without constipation.43 In subsequent studies, probiotics were administered after colonoscopy. Half of these studies reported a reduction in post-colonoscopy gastrointestinal symptoms, such as pain, bleeding, diarrhea, and discomfort, in the probiotics groups than in the placebo groups.44-49 Subgroup analyses showed that patients who have preexisting symptoms such as abdominal pain before colonoscopy benefited more in reducing post-colonoscopy symptoms from probiotic administration than patients who did not have preexisting symptoms.44,45 In a large open-label clinical trial involving 3,197 participants with multi-strain probiotics (Lactobacillus plantarum LP01, Lactococcus lactis subspecies cremoris LLC02, Lactobacillus delbrueckii LDD01, 2×10¹⁰ [CFU]) and 1,612 participants without any treatment, 4 weeks of probiotic administration significantly decreased abdominal pain, abdominal discomfort, bloating, and bowel alteration at the 2nd and 3rd week after colonoscopy compared to no treatment.50

Table 2.

Randomized controlled trials investigating the effect of probiotics on colonoscopy-induced gastrointestinal symptoms and gut microbiota alterations

In addition to alleviating symptoms, several studies have found that post-colonoscopy probiotic administration contributes to reversing changes in the gut microbiota to varying degrees.46-49 Specifically, probiotic administration has been found to increase α-diversity, which is reduced by colonic preparation. However, the findings on its effect on β-diversity have been inconsistent.46-49 Certain probiotic strains, such as a mixture of Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis, and Bacillus cereus, have been shown to promote a rapid decrease in Proteobacteria, which typically increase after colonic preparation.46 Probiotics have also been found to contribute to the restoration of various bacterial genera, including Faecalibacterium, Ruminococcus, Blautia, Gemmiger, Bacteroides, Roseburia, and Parabacteroides.46,47 However, outcomes have varied among studies, with one study reporting that the administered probiotic strain was not detectable in the feces of a significant proportion of patients.48 It is important to acknowledge that the effectiveness of probiotics can be influenced by various host factors, notably, gastrointestinal transit.33,51,52 Consequently, the effects of probiotic administration after colonoscopy may differ from those seen in the general population. Moreover, the timing of administration is crucial for optimal efficacy. A small study of irritable bowel syndrome with diarrhea demonstrated that probiotic administration immediately after colonoscopy had a sustained beneficial effect on stool consistency 6 months later than administration 1 month after the procedure.53

CONCLUSIONS AND SUGGESTIONS FOR FUTURE STUDIES

We conducted a thorough review of studies on alterations in the gut microbiota following colonoscopy and discussed their possible mechanisms. The process of colonoscopy induces significant alterations in the gut microbiota due to several factors, such as the rapid evacuation of colonic content, increased osmolality, and mucus depletion caused by bowel preparation, and exposure to oxygen during the colonoscopy. Although these changes usually revert to the baseline and are often clinically insignificant, their long-term effects must be investigated, particularly regarding the role of post-colonoscopy symptoms and differences between younger and older age groups.54

Split-dose bowel preparation appears to be more effective in reducing the effects of colonoscopy-induced gut microbiota changes than single-dose regimens. Moreover, probiotic administration following colonoscopy may be beneficial. However, the question of whether probiotics are beneficial for all patients after colonoscopy is still debated due to the transient nature of gastrointestinal symptoms and gut microbiota alterations associated with colonoscopy. It is essential to recognize that post-colonoscopy gastrointestinal symptoms are more prevalent among individuals with preexisting diseases and lower baseline α-diversity, and that the gut microbiota may not recover completely in certain populations.4,5,17,18 Probiotics offer greater benefits to individuals who experience gastrointestinal symptoms before a colonoscopy.44,45 Therefore, probiotic administration immediately after a colonoscopy may be a viable option for certain patients, particularly those predisposed to persistent gastrointestinal disturbances.

Notes

Conflicts of Interest

The authors have no potential conflicts of interest.

Funding

This work was supported by Wonkwang University 2023.

Author Contributions

Conceptualization: HHJ, MYL, YSK; Data curation: HHJ, YSK; Formal analysis: SEH, DHY, YSK; Funding acquisition: MYL; Investigation: all authors; Writing–original draft: HHJ, YSK; Writing–review & editing: HHJ, SEH, DHY, YSK.

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Table 1.

Studies associated with the effects of bowel preparation and colonoscopy on gut microbiota

Study	Subject	Age (yr)	BP agent	Sample for microbiota		Detection method		Gut microbiota change after CS or diarrhea compared to baseline			Recovery after CS
Study	Subject	Age (yr)	BP agent	Type	Collection timing	Detection method	α-Diversity	β-Diversity	Phylum level	Below phylum level	Recovery after CS
Mai et al. (2006)9	5 HC	NA	NA	S	Before, during, 6–8 w after CS	V3, V6–V8, DGGE	NA	Significantly different	NA	NA	NA
Harrell et al. (2012)10	12 HC	25–48	PEG (Golytely) 4 L	M	Before, during CS	TRFLP	↓ OTU, ↓ Shannon index	NA	→	Significantly different	NA
Gorkiewicz et al. (2013)11	4 HC	36–47	PEG (Forlax) 50 g tid for 3 d	S, M	7 d before, 3rd d on PEG, 7 d after stopping PEG	V1–V2, FLX system	• M: → richness, → evenness	Significantly different	• M:↓ Bacteroidetes, ↑ Proteobacteria	• M: ↓ Faecalibacterium, ↑ Pseudomonas, ↑ Acinetobacter, ↑ Arcobacter, ↑ LAB	• ↓ Species richness in stool persisted during the 1 wk after diarrhea
Gorkiewicz et al. (2013)11	4 HC	36–47	PEG (Forlax) 50 g tid for 3 d	S, M	7 d before, 3rd d on PEG, 7 d after stopping PEG	V1–V2, FLX system	• S:↓ richness, → evenness	Significantly different	• M:↓ Bacteroidetes, ↑ Proteobacteria	• S: ↑ Faecalibacterium
O'Brien et al. (2013)12	15 Patients (UC, abdominal pain, IDA, polyp)	46–69	PEG 2 L+bisacodyl 10 mg	S	1 mo before, 1 wk before, 1 wk after, 1 mo after, 3–6 mo after CS	V1–V3 region, DGGE	→	→	NA	NA	NA
Jalanka et al. (2015)13	23 HC	25–27	PEG (Moviprep) 2 L, split or single-dose	S	1 d before, immediately after, 14 d after, 28 d after CS	V1 & V6, phylogenic microarray	→	→	↓ No. of bacteria & methanogenic archaea, ↑ G(+)/G(–) ratio, ↑ Proteobacteria	↓ Bacilli, ↓ Clostridium cluster IV, ↑ Clostridium cluster IX & XIVa	• Restored after 14 d and 28 d
Jalanka et al. (2015)13	23 HC	25–27	PEG (Moviprep) 2 L, split or single-dose	S	1 d before, immediately after, 14 d after, 28 d after CS	V1 & V6, phylogenic microarray	→	→			• Split dose has a less disturbing and better recovery than the single dose
Shobar et al. (2016)14	18 HC & patients (5 CD, 3 UC)	49–55.4	11 PEG, 7 Sodium phosphate	S, M	Before, after SS	FLX platform	• M (IBD): ↓ Shannon index	Significantly different only in IBD	NA	NA	NA
Shobar et al. (2016)14	18 HC & patients (5 CD, 3 UC)	49–55.4	11 PEG, 7 Sodium phosphate	S, M	Before, after SS	FLX platform	• M (HC): ↓ PD-WT	Significantly different only in IBD	NA	NA	NA
Drago et al. (2016)15	10 HC	40–68	PEG 4 L, single-dose	S	Before, immediately after, 1 mo after CS	V2-4-8, V3-6, V7–9. Ion Torrent PGM system	↓ Shannon index	NA	• Immediately after: ↓ Firmicutes, ↑ Proteobacteria	• Immediately after: ↑ γ-Proteobacteria, ↑ Coriobacteriia, ↑ Enterobacteriaceae, ↓ Clostridia, ↓ Lactobacillaceae, ↓ Porphyromonodaceae, ↓ Veillonellaceae	• Shannon index recovered at 1 mo after
Drago et al. (2016)15	10 HC	40–68	PEG 4 L, single-dose	S	Before, immediately after, 1 mo after CS	V2-4-8, V3-6, V7–9. Ion Torrent PGM system	↓ Shannon index	NA	• Immediately after: ↓ Firmicutes, ↑ Proteobacteria	• 1 mo after: ↓ γ-Proteobacteria, ↓ α-Proteobacteria, ↓ Lactobacillaceae, ↓ Enterobacteriaceae, ↓ Streptococcaceae, ↑ Rikenellaceae, ↑ Eubacteriaceae	• Disturbed phylum composition recovered at 1m after but not completely at class and family level
Shaw et al. (2017)16	18 HC & patients (CD, UC, IBS, JPC, food allergies, recurrent mucosal candidiasis)	4–17	Sodium picosulfate with MgC and senna	S, M, rectal swab	Before, immediately after, >2 wk after CS	V3–V5, GS Junior	→	→	→	• Immediately after: ↑ Bacteroidia, ↑ Faecalibacterium, ↓ γ-Proteobacteria, ↓Ruminococcus, ↓ Escherichia, ↓ Pseudobutyrivibrio, ↓ Subdoligranulum	NA
Shaw et al. (2017)16		4–17	Sodium picosulfate with MgC and senna	S, M, rectal swab	Before, immediately after, >2 wk after CS	V3–V5, GS Junior	→	→	→	• >2 wk after: ↑ Christensenellaceae	NA
Chen et al. (2018)17	20 Overweight adults (mean BMI 28.92 kg/cm²)	40.5	Phospho-Soda (Fleet)+water 3–4 L, split-dose	S	Before, 7 d after, 1 mo after CS	V4, Illumina MiSeq	• Bacteroides-dominant group: →	→	→	• Prevotella-dominant group:	• Shannon index recovered 28 d after
							• Prevotella-dominant group:			↑ Bacteroides, ↓ Prevotella in 7 d after
							↑Shannon index 7 d after, ↓richness 28 d after
Kim et al. (2021)18	24 HC	42.8±11.9	PEG (Coolprep)+20 g AA solution, 4 L, split-dose	S	Before, 7 d after, 1 mo after CS	V3–V4, Illumina MiSeq	• Baseline α-diversity: Cx(–)>Cx(+)	→	• Baseline F/B ratio: Cx(+) > Cx(–)	Similar pattern with the phylum level	• Cx(+) group: F/B ratio recovered 28 d after
							• Cx(–) group: ↓ Simpson index		• Cx(+) group:
							• Cx(+) group: →		↓ F/B ratio 7d after, ↑ Proteobacteria 28 d after
Batista et al. (2022)19	55 HC & patients (16 MC, 16 BAD, 11 FDr)	62.0±1.5	PEG, split-dose	S	Before, 30 d after CS	V4, Illumina MiSeq	•HC: → Shannon index, → Chao1 index	NA	NA	NA	NA
Batista et al. (2022)19	55 HC & patients (16 MC, 16 BAD, 11 FDr)	62.0±1.5	PEG, split-dose	S	Before, 30 d after CS	V4, Illumina MiSeq	•MC & FDr: ↑ Shannon index	NA	NA	NA	NA
Nalluri-Butz et al. (2022)20	15 HC & patients (7 hematochezia, 1 CDr)	48.3±15.3	PEG (14 Miralax+MgC, 1 GoLYTELY)	S	Before, during, 10 d after, 30 d after, 180 d after CS & OP	V4, Illumina MiSeq	→	→	→	→	NA
Powles et al. (2022)21	11 Patients (9 bowel habit changes &/or diarrhea, 2 UC)	41	PEG (MoviPrep) 2 L, split-dose	S, U	Before, 3 d after, 6 wk after CS	V1–2, Illumina MiSeq	↓ Shannon index at 3 d after	→	→	→	• Shannon index recovered 6 wk after
Powles et al. (2022)21	11 Patients (9 bowel habit changes &/or diarrhea, 2 UC)	41	PEG (MoviPrep) 2 L, split-dose	S, U	Before, 3 d after, 6 wk after CS	V1–2, Illumina MiSeq	↓ Shannon index at 3 d after	→	→	→	• Fecal & urine metabolite was not affected by CS
Zou et al. (2023)22	19 HC	10.01±3.47	PEG, ≤3 L, split-dose	S	1 d before, 2 d after, 2 wk after, 4 wk after CS	Illumina MiSeq	• ↓ Shannon index at 2 d after	→	→	• 2 d after: ↑Escherichia coli, ↑Bacteroides fragilis, ↑Veillonella parvula, ↓Intertinibacter bartlettii	• Shannon index recovered at 2 wk after
Zou et al. (2023)22	19 HC	10.01±3.47	PEG, ≤3 L, split-dose	S	1 d before, 2 d after, 2 wk after, 4 wk after CS	Illumina MiSeq	• ↓ Shannon index at 2 d after	→	→	• 2 wk after:↑Eubacterium	• Disturbed composition restored at 2, 4 wk after
Bacsur et al. (2023)23	41 HC & patients (9 CD, 13 UC)	UC 45.54±12.46, CD 32.03±7.59	Sodium picosulfate and MgO (10 mg and 3.5 g per dose), split-dose	S	1 wk before, 3 d after, 4 wk after BP	V4, Illumina MiSeq	• UC: ↑ Shannon index at 4 wk after	→	→	• HC: ↑ Brucellaceae, ↑ Moraxellaceae, ↑ Alcaligenaceae	NA
Bacsur et al. (2023)23	41 HC & patients (9 CD, 13 UC)	UC 45.54±12.46, CD 32.03±7.59		S	1 wk before, 3 d after, 4 wk after BP	V4, Illumina MiSeq	• CD & HC: → Shannon index	→	→	• Relapsing IBD after CS: ↓B ifidobacterium, ↓Lactococcus, ↑ Enterococcaceae, ↑ Streptococcaceae	NA

Values are presented as mean±standard deviation unless otherwise indicated.

BP, bowel preparation; CS, colonoscopy; HC, healthy control; NA, non-available; S, stool; DGGE, denaturing gradient gel electrophoresis; PEG, polyethylene glycol; M, mucosal biopsy; TRFLP, terminal restriction fragment length polymorphism; ↑, increase; ↓, decrease; →, no significant change; OTU, operative taxonomic units; LAB, lactic acid bacteria; CD, Crohn's disease; UC, ulcerative colitis; IDA, iron deficiency anemia; SS, sigmoidoscopy; IBD, inflammatory bowel disease; PD-WT, phylogenetic diversity-whole tree metric; IBS, irritable bowel syndrome; JPC, Juvenile polyposis coli; AA, ascorbic acid; Cx, complication; MC, microscopic colitis; BAD, bile acid diarrhea; FDr, functional diarrhea; CDr, chronic diarrhea; MgC, magnesium citrate; MgO, magnesium oxide; U, urine; NA, non-available.

Table 2.

Randomized controlled trials investigating the effect of probiotics on colonoscopy-induced gastrointestinal symptoms and gut microbiota alterations

Study	Subject	Age (yr)	BP agent	Probiotics	Effect on post-colonoscopic symptom	Gut microbiota change compared to baseline after CS compared to baseline^a)
Study	Subject	Age (yr)	BP agent	Probiotics	Effect on post-colonoscopic symptom	α-Diversity	β-Diversity	Phylum level	Below phylum level	Recovery
Lee et al. (2010)43	51 C(+) PRG	40.5±11.4	NaP solution (Solin), split-dose	Bacillus subtilis 1×10⁹ cfu & Streptococcus faecium 9×10⁹ cfu bid for 2 wk before CS	• C(+): lower symptom in PRG than in PLG	NA	NA	NA	NA	NA
	53 C(+) PLG	42.2±11.7			• C(–): no difference between PRG & PLG
	53 C(–) PRG	40.6±10.6
	54 C(–) PLG	41.7±10.8
D'Souza et al. (2017)44	133 HC PRG	61.6±13.8	Sodium picosulfate	Lactobacillus acidophilus NCFM 1.25×10¹⁰ & Bifidobacterium lactis Bi-07 1.25×10¹⁰ cfu qd for 2 wk after CS	• Lower pain days in PRG than PLG	NA	NA	NA	NA	NA
D'Souza et al. (2017)44	126 HC PLG	60.1±12.8	Sodium picosulfate		• Patients with preexisting abdominal pain benefit from probiotics	NA	NA	NA	NA	NA
Mullaney et al. (2019)45	75 HC PRG	58.6	Sodium picosulphate+PEG (Prep kit C)+colonoscopy with CO₂	Lactobacillus acidophilus NCFM 1.25×10¹⁰ & Bifidobacterium lactis Bi-07 1.25×10¹⁰ cfu qd for 2 w after CS	• No difference between PRG & PLG	NA	NA	NA	NA	NA
Mullaney et al. (2019)45	75 HC PLG	58.2	Sodium picosulphate+PEG (Prep kit C)+colonoscopy with CO₂		• Lower incidence of bloating in PRG who had preexisting GI symptoms	NA	NA	NA	NA	NA
Deng et al. (2020)46	16 HC PRG	53.5	2 L PEG single-dose	Bifidobacterium infantis >0.5×10⁶ cfu, Lactobacillus acidophilus >0.5×10⁶ cfu, Enterococcus faecalis >0.5×10⁶ cfu, Bacillus cereus >0.5×10⁵ cfu tid, for 5–7 d after CS	NA	• PLG: ↓ 7 d after CS	• PLG: significantly differs compared with baseline after 7 d	•PLG: ↑ Proteobacteria, ↑ Actinobacter	NA	• PLG: Proteobacteria & Actinobacter were recovered,
	16 HC PLG	48.2				• PRG: ↑ 7 d after CS	• PRG: restore to baseline level after 7 d	• PRG: ↑ Proteobacteria, ↓ Firmicutes		↑ Bifidobacterium, ↑ Streptococcus, ↑ Acinetobacteria, ↓ Fecalibacterium 7 d after CS
										• PRG: Proteobacteria was sharply recovered, ↑ Bacteroidetes, ↑ Bifidobacterium, ↑ Fecalibacterium
Liu et al. (2022)47	48 CP(+) PRG	58.67±9.44	NA	Bifidobacterium animalis subsp. lactis MH-02 2×10⁹ cfu qd, for 7 d after CS	• No difference between PRG & PLG	PRG>PLG	Significantly differences between PRG & PLG	NA	↑ Bifidobacterium, ↑ Faecalibacterium, ↑ Dorea, ↑ Roseburia, ↑ Gemmiger, ↓ Clostridium in PRG than PLG	Compared to control
	52 CP(+) PLG	59.25±11.33			• Higher laxative use in PLG than PRG					• ↓ Bifidobacterium in both groups, but PBG>PLG
										• ↓ Ruminococcus, ↓ Blautia, ↓ Gemmiger,↑ Clostridium in PLG, but → in PBG
Labenz et al. (2022)48	45 HC PRG	59.3	PEG (Moviprep or Plenvu)+colonoscopy with CO₂	Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Enterococcus faecium W54, Lactobacillus acidophilus W37, Lactobacillus rhamnosus WGG, Lactococcus lactis W19, 2.7×10¹⁰ cfu bid for 30 d after CS	• Lower constipation, pain, bloating, diarrhea, and general discomfort in PRG than PLG	• PLG: → 30 d after CS	• PLG: → 30 d after CS	NA	• PRG: ↑ Clostridioides sp. CAG:417, ↓ Bacillales bacterium UBA660, ↓ Duodenibacillus,	NA
	42 HC PLG	59.9				• PRG: → 30 d after CS	• PRG: → 30 d after CS		↓ Ruminiclostridium, ↓ uncultured Clostridioides sp. UMGS1663
									• PLG: ↓ Clostridioides sp. CAG:417
Son et al. (2023)49	26 HC PRG	54.4±7.8	PEG+AA	Lactobacillus acidophilus CBT LA1, Lactobacillus rhamnosus CBT LR5, Bifidobacterium lactis CBT BL3, Bifidobacterium longum CBT BG7, Bifidobacterium bifidum CBT BFs, Streptococcus thermophilus CBT ST3, 1×10¹⁰ cfu, for 30 d before CS	• Lower symptom duration in PRG than PLG	↓ After 1–2 d after CS in PLG only compared to 2–3 d before	→	NA	Higher number of↓taxa after CS in PLG than PRG	• PRG: restored to baseline
Son et al. (2023)49	25 HC PLG	53.1±8.3	PEG+AA		• Lower symptom duration in PRG than PLG	↓ After 1–2 d after CS in PLG only compared to 2–3 d before	→	NA	Higher number of↓taxa after CS in PLG than PRG	• PLG: ↓ few taxa including Gastranaerophilales & Clostridia_UCG_014

Values are presented as mean±standard deviation unless otherwise indicated.

BP, bowel preparation; CS, colonoscopy; C, constipation; PRG, probiotics group; PLG, placebo group; PBG, probiotic group; NaP, sodium phosphate; cfu, colony-forming unit; bid, twice daily; tid, three times daily; qd, once daily; NA, non-available; HC, healthy control without colon pathology, screening or post-polypectomy surveillance colonoscopy; PEG, polyethylene glycol; ↑, increase; ↓, decrease; →, no significant change; CP, colonic polyp; AA, ascorbic acid.

^a)

All studies were conducted with stool samples by Illumina MiSeq.