Review
Copyright ©The Author(s) 2023.
World J Gastroenterol. Apr 14, 2023; 29(14): 2078-2100
Published online Apr 14, 2023. doi: 10.3748/wjg.v29.i14.2078
Table 1 Summary of preclinical studies of probiotics
Ref.
Model
Treatment
Dose and duration
Parameters analyzed
Conclusion
Yoo et al[26], 2022DSS-induced colitis in male C57BL/6 miceLactobacillus plantarum, Bifidobacterium longum, and Bifidobacterium bifidum1 × 109 CFU once daily for 5 dCytokines and corticosterone, colonic MPO activity, fecal LPS levelSuppressed colonic inflammation, and fatigue by the suppression of the IL-1β or IL-6 to IL-10 expression ratio and gut bacterial LPS production
Qin et al[27], 2022DSS-induced colitis in miceLactobacillus (Pediococcus pentosaceus, Lactobacillus plantarum, and Weissella cibaria)-DAI, colon length, pathological score, cytokine secretionShowed the potential to treat IBD
Khan et al[28], 2022DSS-induced colitis in mice (C57BL/6)Lactobacillus plantarum-Colitis indexes, IL-17A, IL-17F, IL-6, IL-22, and TNF-α and anti-inflammatory cytokines, i.e., TGF-β, IL-10Restored gut microbiota balance and modulated the resident gut microbiota and immune response
Fei et al[29], 2022DSS-induced colitis in mice (C57/BL6)Ligilactobacillus salivarius Li01 and RSVLi01 (109 CFU/d) and RSV (1.5 g/kg/d)IL-1β and IL-6, TGF-β and IL-17AAn improved synergistic anti-inflammatory effect from the RSV and Li01 combination treatment
Liu et al[30], 2021DSS-induced colitis in mice (C57/BL6)Goji juice fermented by Lactobacillus plantarum, Lactobacillus reuteri and Streptococcus thermophilus20 mL/kg/d for 30 d Pro-inflammatory cytokines and total superoxide dismutase in serum and colon, MPO and glutathione peroxidaseProbiotics-fermentation enhanced the anti-ulcerative colitis function of goji berry juice and modulated gut microbiota
Kim et al[31], 2020DSS-induced colitis in male C57BL/6 miceLactobacillus plantarum CBT LP3 (KCTC 10782BP)1 × 108 bacteria in 0.1 mL PBS once daily for 16 dDAI, analysis of macrophages and T cell subsets gene expression and cytokine profilesEffective anti-inflammatory effects, with increased induction of Treg and restoration of goblet cells, suppression of proinflammatory cytokines
Chen et al[32], 2020DSS-induced colitis in C57BL/6J miceBifidobacterium breve, CCFM6830.2 mL (1010 CFU/d CCFM683, once daily for 2 wkWeight loss, stool consistency and fecal bloodImproved intestinal epithelial barriers, restored gut microbiota
Chen et al[33], 2020DSS-induced colitis in C57BL/6 miceBifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis with (quadruple probiotics, Pqua) or without (triple probiotics, P-tri) aerobic Bacillus cereusB. infantis, L. acidophilus, and E. faecalis (1.5 × 109 CFU respectively) in 200 uL PBS and B. cereus (0.5 × 108 CFU) in 200 uL once daily for 45 dIntestinal inflammation and functions of multiple barriers, including the mucus barrier, and epithelial barrierEffective (Aerobe-contained Pqua was a powerful adjuvant therapy for chronic colitis, via restoring the intestinal microflora and recovering the multi-barriers in the inflamed gut)
Komaki et al[34], 2020MiceLactococcus lactis subsp. lactic JCM58051 mg, 5 mg, 10 mg, 15 mg, or 20 mg, once daily for 1 wkThe survival rate, length, histopathological parameters of the colon, and concentrations of inflammatory cytokines in serumEffective (high-dose administration deteriorates intestinal inflammation)
Silveira et al[35], 2020C57BL/6 miceLactobacillus bulgaricus1 × 109 CFU was diluted in 200 mL of PBS, 3 times per week for 12 wkIntestinal inflammation, cytokines levels were determined from colon and/or tumorRegulates the inflammatory response and prevents Colitis-associated cancer
Table 2 Summary of clinical studies of using probiotics in inflammatory bowel disease patients
Ref.
Treatment
Dose and duration
Parameters analyzed
Conclusion
Agraib et al[43], 2022Lactobacillus and Bifidobacterium species3 × 1010 probiotic capsulesPartial mayo score, CRP, IgA, IL-10, hemoglobin, hematocrit, and RBC levelsSignificantly induced remission in UC patients
Ojetti et al[44], 2022Limosilactobacillus reuteri ATCC PTA 4659Two times a day for 10 dInflammatory markers CRP and calprotectinSignificantly reduced both blood and fecal inflammatory marker
Wu et al[45], 2021Live bacillus licheniformis capsules and live combined Bifidobacterium, lactobacillus, and enterococcus capsules followed by Chamomile capsulesBacillus licheniformis capsules two capsules, three times a day and live combined Bifidobacterium, lactobacillus, and enterococcus capsules two capsules twice a day. Probiotics consumed at a level of 107 CFU/mLLeiden Index of Depression Sensitivity, Beck Depression Inventory questionnairesProbiotics tend to improve cognitive reactivity to the sad mood in CD patients
Bamola et al[46], 2021Bacillus coagulans Unique IS-22 billion-CFU/capsule twice in day 4 wkPresence of beneficial gut bacteria, serum cytokines, symptoms of the diseaseShowed beneficial effect when administered along with standard medical treatment
Waal M van der et al[47], 2019Nine bacterial strains (Bifidobacterium bifidum W23; Bifidobacterium lactis W51; Bifidobacterium lactis W52; Lactobacillus acidophilus W22; Lactobacillus casei W56; Lactobacillus paracasei W20; Lactobacillus plantarum W62; Lactobacillus salivarius W24; Lactobacillus lactis W19)7.5 × 109 CFU per 3 g in powder form, once daily for 6 wkQuality of life from a patient perspective (semi-structured interviews)Effective
Kamarli Altun et al[48], 2022Enterococcus faecium, Lactobacillus Plantarum, Streptococcus thermophilus, Bifidobacterium lactis, Lactobacillus acidophilus, Bifidobacterium long, and FOSProbiotic strains (3 × 109 CFU) and FOS (225 mg/ tablet), 1 tablet twice a day for 8 wkHemoglobin, leukocyte, neutrophil-to-lymphocyte ratio, sedimentation, and CRP, clinical and endoscopic activity indicesEffective
Sun et al[49], 2018Clostridium butyricum420 mg per capsule, 1.5 × 107 CFU/g, 3 capsules 3 times a day for 4 wkChange from baseline in IBD symptoms, quality of life, stool consistency, and frequencyEffective
Matsuoka et al[50], 2018Bifidobacterium breve strain Yakult and Lactobacillus acidophilus10 billion bacteria of Bifidobacterium breve and 1 billion bacteria of Lactobacillus acidophilus, one pack per day for 48 wkClinical procedure (change in abdominal symptom score from baseline. Sutherland DAI subscore, change in abdominal symptom scores (passage of flatus and bloating), and intestinal microbiotaLess significant effect
Table 3 Summary of preclinical studies of prebiotics
Ref.
Model
Type of treatment
Composition
Dose
Parameters analyzed
Conclusion
Cui et al[57], 2021DSS-induced colitis in C57BL/6J micePolysaccharide from Scutellaria baicalensis GeorgiMannose, ribose, rhamnose, glucuronic acid, glucose, xylose, arabinose, fucose50 and 200 mg/kg once daily for 10 dBody weight, loose stools, morbidity, hematochezia, and the DAIEffective (attenuated body weight loss, reduced DAI, ameliorated colonic pathological damage, and decreased MPO activity)
Tolonen et al[58], 2022DSS-induced colitis in male C57Bl/6 miceSynthetic glycansFOS, GOS, XOS, pullulan, and lactulose1% (v/v) glycans (days 7-14)Weight loss, scores of diarrhea, endoscopy, and colonic histologySynthetic glycans increase survival, reduce weight loss, and improve clinical scores in mouse models of colitis
Qian et al[59], 2022DSS-induced colitis in male C57Bl/6 miceGOS, FOS along with FMTFMT alone or combined with various ratios of GOS, and FOS-DAI scores, histology, protein or mRNA expression levels of FFAR3 and ZO-1, a tight junction proteinTreatment with FMT plus a prebiotic blend restores thestructure of the intestinal flora and increased the levels of acetic acid, butyric acid, FFAR3, and ZO-1
Liu et al[60], 2016DSS-induced colitis in male C57BL/6 miceAlpha D-glucan from marine fungus Phoma herbarum YS4108Glucopyranose40 mg/kg/d once daily for 1 wkDAI scores, histology immunohistochemistry analysis, evaluation of SOD and MDA activities, and determinations of inflammatory cytokinesEffective (significantly increased butyrate, isovaleric acid levels, and prominent alterations on specific microbiota)
He et al[61], 2020DSS-induced colitis in male C57BL/6 miceStachyoseStachyose1.5 g/kg/d for 28 dInflammatory cytokines including IL-6, IL-10, IL-17a, and TNF-αIncreased beneficial microbiota and bacterial diversity to alleviate acute colitis in mice
Kanwal et al[62], 2019Dictyophora indusiate polysaccharideGlucose 59.84%, mannose 23.55%, and galactose 12.95%Low dose 10 mg/kg and (high dose 33 mg/kg once daily for 2 wkAssessment of DAI, histological, analysis of goblet cells and mucus layer thickness, cytokinesEffective
Li et al[63], 2020Male C57BL/6 miceFMG or dealcoholized muscadine wineFMG: Fructose 34.7% glucose 31%, sucrose 9.9%. DMW: Fructose, sucrose, and glucose not detectedFMG (7%, w/w) or DMW (5.5%, v/ w) for 3 wkBodyweight, stool consistency and bleeding, DAI, short-chain fatty acids in feces, and Mucin 2 and IgA in fecesEffective (reduced dysbiosis in the colon)
K-da et al[64], 2020Male C57BL/6 miceGFOMonosaccharide composition in the GFO was D-galactose100, 500, or 1000 mg/kg once daily for 2 wkGI transit time, ex vivo propulsive motility, in vitro colonic smooth muscle contractility, the composition of colonic microbiota, and production of SCFAsEffective (prevented and attenuated colitis symptoms and GI dysmotility, reducing populations of harmful bacteria and increasing SCFAs)
Table 4 Summary of clinical studies of using prebiotics in inflammatory bowel disease patients
Ref.
Type of treatment
Dose
Parameters analyzed
Conclusion
Valcheva et al[68], 2022β-fructans (oligofructose and inulin)15 g/d for 6 moMayo score. FCP, along with stool metabolitesDid not prevent symptomatic relapses in UC patients but reduced the severity of biochemical relapse and increased anti-inflammatory metabolites
Pietrzak et al[69], 2022Sodium butyrate150 mg sodium butyrate twice a day for 12-wkDAI, FCPAs adjunctive therapy, it did not show efficacy in newly diagnosed children and adolescents with IBD
Vernero et al[70], 2020Oral microencapsulated sodium butyrate (BLM)Dose of two capsules/day for 12 mo (500 mg of BLM for each capsule)DAI, FCP, CRPBLM supplementation appears to be a valid add-on therapy to maintain remission in patients with UC
Valcheva et al[71], 2019Oligofructose-enriched inulin7.5 g (n = 12) or 15 g (n = 13) daily oral oligofructose-enriched inulin for 9 wkMayo score, endoscopic activity and FCP15 g/d dose inulin-type fructans produced functional but not compositional shifts of the gut microbiota. Controlled studies for the use of β-fructans as an adjunct therapy in patients with active UC are required
Azpiroz et al[72], 2017scFOS5 g per sachet, twice daily for 4 wkRectal sensitivity, anxiety/depression, quality of life scores, and composition of fecal microbiotaLess significant (scFOS on rectal sensitivity may require higher doses and may depend on the subgroup)
Table 5 Summary of preclinical studies of synbiotics
Ref.
Model
Probiotics
Prebiotics
Dose
Parameters analyzed
Conclusion
Xue et al[80], 2023DSS-induced colitis in miceLactobacillus plantarum LP90Soluble dietary fiber obtained from Lentinula edodes by products1 × 109 CFU/kgDAI, histological studies, IL-10, IL-17, IgA levels, TNF-αAlleviated colitis
Ivanovska et al[81], 2017DSS-induced colitis in C57BL/6J miceBifidobacterium infantis and Bifodobacterium longumEqual parts FOS, GOS and XOS0.5 × 109 CFU Probiotics and 2.5 g of prebiotics for 1 moGut microbiome, cecal and fecal SCFAsIncreased the diversity of the microbiome and be associated with more SCFAs, and less gut inflammation
Seong et al[82], 2020Chronic restraint stress in male Wistar ratsL. paracaseiOpuntia humifusa extract (mucilage + pectin)L. paracasei (1 × 1010 CFU/g) & (10.0/30.0 mg%, w/w) of Opuntia humifusa extract once daily for 4 wkFecal microbial analysis, serum corticosterone levels, TNF-α levels in the colon tissueEffective (greater abundance of L. paracasei in fecal microbial analysis, lower serum corticosterone levels, lower TNF-α levels in the colon tissue
dos Santos Cruz et al[83], 2020IL 10- knockout miceVSL#3Yacon (6% FOS + inulin)VSL#3 (109 CFU/d) + PBY (6% FOS and inulin) for 13 wkManifestations of colitis, colon histology, expression of antioxidant enzymes, production of organic acids, and intestinal microbiotaPreservation of intestinal architecture, improve intestinal integrity, increased expression of antioxidant enzymes and concentration of organic acids
Wang et al[84], 2019DSS-induced colitis in C57BL/6J miceLactobacillus acidophilus, L. Rhamnosus, and Bifidobacterium lactisInulinProbiotics: 1.0 × 109 CFU per day per mice, and prebiotic 5 × 108 CFU/dPathologic scores, mucosal floraIncreased the proportion of helpful bacteria and regulated the balance of intestinal microbiota, reduced the degree of inflammation in acute colitis mice
Son et al[85], 2019DSS-induced colitis in female BALB/c miceLGGTagatose109 CFU/mL of LGG and 25 mg of tagatose once in 2 d for 3 wkBody weight, food intake, rectal bleeding, stool conditions, blood in stool, expression of proinflammatory cytokinesEffective (gut microbiota composition recovered from the dysbiosis caused by DSS treatment)
Ivanovska et al[81], 2017TNBS-induced colitis in Wistar ratsL. Casey 01Oligofructose-enriched inulin1 mL containing non-encapsulated probiotic/prebiotics once daily for 2 wkAssessment of colonic damage, inflammation scoring, MPO and microbiological studiesEffective
Table 6 Summary of clinical studies of using synbiotics in inflammatory bowel disease patients
Ref.
Probiotics
Prebiotics
Dose
Parameters analyzed
Conclusion
Amiriani et al[86], 2020Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus bulgaricus, Bifidobacterium breve, Bifidobacterium longum, Streptococcus thermophilesFOSLactocare capsule twice daily for 8 wkDAIMitigated symptoms in patients with UC and suggested to use pre-probiotics in the standard treatment, particularly in those with more than five years of the disease
Kamarlı Altun et al[87], 2019Enterococcus faecium, Lactobacillus plantarum, Streptococcus thermophilus, Bifidobacterium lactis, Lactobacillus acidophilus, Bifidobacterium longumFOS3 × 109 CFU probiotic and 225 mg/tablet prebiotic for 8 wkHemoglobin, leukocyte, neutrophil-to-lymphocyte ratio, sedimentation, and CRP and clinical and endoscopic activity indicesImprovement in clinical activity