GLP Digest+

Effects of Dietary Fiber Supplementation on Gut Microbiota and Bowel Function in Healthy Adults: A Randomized Controlled Trial

Study Type: Randomized controlled trial (RCT)

Abstract/Summary: This RCT evaluated the effects of prebiotic fiber supplementation on gut microbiota composition and bowel function in healthy adults. Participants received either prebiotic fiber blend or placebo for 4 weeks.

Key Results:

• Prebiotic fiber significantly increased beneficial Bifidobacterium populations
• Improved stool consistency and bowel movement regularity
• Enhanced overall gastrointestinal comfort scores
• No adverse gastrointestinal events reported

Source: https://www.mdpi.com/2076-2607/13/9/2068

Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss

Study Type: Pooled analysis of Phase 3 RCTs (STEP 1-3 trials)

Abstract/Summary: This study evaluated gastrointestinal (GI) adverse events with once-weekly semaglutide 2.4 mg in adults with overweight or obesity, pooling data from the STEP 1-3 trials (n=2,117 semaglutide, n=1,262 placebo) over 68 weeks.

Key Results:

• Nausea: 43.9% vs. 16.1% (semaglutide vs. placebo)
• Diarrhea: 29.7% vs. 15.9%
• Vomiting: 24.5% vs. 6.3%
• Constipation: 24.2% vs. 11.1%
• Most GI AEs (99.5%) were non-serious
• 98.1% were mild-to-moderate in severity
• GI AEs occurred most frequently during/shortly after dose escalation

Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC9293236/

Dried chicory root improves bowel function, benefits intestinal microbial trophic chains and increases faecal and circulating short chain fatty acids in subjects at risk for type 2 diabetes

Study Type: Randomized, placebo-controlled, parallel trial (RCT)

Abstract/Summary: This study investigated the impact of prebiotic fiber (containing ~85% fiber, of which 70% is native inulin) in 55 subjects at risk for type 2 diabetes. Participants received either 30g/day dried chicory root or isocaloric maltodextrin placebo for 3 weeks.

Key Results:

• Faecal total SCFA increased by 25.7% (+13.02 ± 6.26 mmol/kg; p=0.023)
• 3-4 fold increases in Bifidobacterium and Anaerostipes species (known SCFA producers)
• Improved bowel function and regularity
• Enhanced gut barrier support through SCFA production

Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC11407914/

Xylooligosaccharide increases bifidobacteria but not lactobacilli in human gut microbiota

Study Type: Double-blind, randomized, placebo-controlled trial (RCT)

Abstract/Summary: This study was conducted to determine the tolerance and effects of the prebiotic xylooligosaccharide (XOS) on the composition of human colonic microbiota, pH, and short chain fatty acids (SCFA) in order to determine whether significant changes in the microbiota would be achievable without side effects. Healthy adult subjects (n=32) were recruited in a double-blind, randomized, placebo-controlled study. Subjects received 1.4g XOS, 2.8g XOS, or placebo in daily doses for 8 weeks.

Key Results:

• XOS demonstrated significant effects at 1.4g and 2.8g daily doses — substantially lower than the 10-20g required for FOS or GOS to achieve similar bifidogenic effects
• Bifidobacterium counts increased significantly in both XOS groups compared to placebo
• XOS was tolerated without significant gastrointestinal side effects
• Authors concluded: "The low dose required and lack of gastrointestinal side effects makes the use of XOS as a food supplement feasible"
• Bifidobacterium counts increased 21% from baseline at 4 weeks and 17% at 8 weeks (high-dose group)
• No increase in Lactobacillus — demonstrating selectivity
• No increase in Clostridium (harmful bacteria)
• Significant increases in beneficial bacteria: Bacteroides fragilis group, Faecalibacterium sp. (butyrate-producing), and Akkermansia sp. (gut health bacterium)
• Bifidobacterium longum was the most commonly isolated species (81% of specimens)

Source: https://pubs.rsc.org/en/content/articlehtml/2014/fo/c3fo60348b

Xylooligosaccharide supplementation alters gut bacteria in both healthy and prediabetic adults: a pilot study

Study Type: Double-blind, randomized, placebo-controlled trial (RCT)

Abstract/Summary: This study evaluated the effect of the prebiotic xylooligosaccharide (XOS) on the gut microbiota in both healthy and prediabetic (Pre-DM) subjects. Pre-DM (n=13) or healthy (n=16) subjects were randomized to receive 2g/day XOS or placebo for 8 weeks. Stool from all subjects at baseline and week 8 was analyzed using Illumina MiSeq sequencing.

Key Results:

• Within 8 weeks, XOS significantly modified gut microbiota in both healthy and prediabetic subjects
• 40 bacterial taxa were identified as Pre-DM associated; XOS reversed/reduced changes in several of these
• XOS significantly decreased abundance of harmful bacteria: Howardella, Enterorhabdus, and Slackia
• XOS significantly increased beneficial Blautia hydrogenotrophica
• Significant changes at 1 phylum, 3 classes, 7 families, 23 genera, and 25 species levels in healthy subjects

Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC4528259/

Xylo-oligosaccharides alone or in synbiotic combination with Bifidobacterium animalis subsp. lactis induce bifidogenesis and modulate markers of immune function in healthy adults

Study Type: Double-blind, placebo-controlled, randomized, factorial cross-over study (RCT)

Abstract/Summary: A candidate prebiotic (xylo-oligosaccharide, XOS, 8g/d) was given to healthy adults (25-65 years) for 21 days. The aim was to identify the effect of the supplements on bowel habits, self-reported mood, composition of the gut microbiota, blood lipid concentrations, and immune function.

Key Results:

• XOS supplementation increased mean bowel movements per day (P=0.009)
• Did NOT alter symptoms of bloating, abdominal pain, or flatulence compared to placebo
• No reported adverse events compared with maltodextrin supplementation
• Significantly increased faecal bifidobacterial counts (P=0.008)
• Significantly increased participant-reported vitality (P=0.003) and happiness (P=0.034)

Source: https://pubmed.ncbi.nlm.nih.gov/24661576/

Investigating the response of the butyrate production potential to major fibers in dietary intervention studies

Study Type: Systematic pooled analysis of 14 randomized intervention studies

Abstract/Summary: This pooled analysis harmonized 16S rRNA gene data from 14 intervention studies (n=7 for inulin-type fructans, n=5 for resistant starch, n=2 for arabinoxylan-oligosaccharides) to reveal taxa stimulated by these substrates and SCFA production potential.

Key Results:

• Inulin-type fructans showed significantly increased butyrate production potential (p<0.05) via increase in bacteria exhibiting the enzyme butyryl-CoA:acetate CoA-transferase
• Butyrate production was governed by Faecalibacterium and Anaerostipes species specifically stimulated by ITF
• Confirms that upon fermentation, inulin produces lactate and SCFAs, including acetate, butyrate, and propionate

Source: https://www.nature.com/articles/s41522-024-00533-5

Inulin-enriched pasta improves intestinal permeability and modifies the circulating levels of zonulin and glucagon-like peptide 2 in healthy young volunteers

Study Type: Randomized, double-blind, crossover controlled trial (RCT)

Abstract/Summary: Twenty healthy young male volunteers completed a randomized, double-blind crossover study consisting of a 2-week run-in period and two 5-week study periods (11% inulin-enriched pasta or control pasta), with an 8-week washout period between treatments. Intestinal barrier function was assessed by lactulose-mannitol excretion in urine.

Key Results:

• Urinary lactulose recovery was significantly lower in the inulin group (indicating improved barrier function)
• Lactulose-mannitol excretion ratio was significantly decreased compared to control and baseline
• Zonulin serum values were significantly lower in the inulin group (zonulin increases permeability when elevated)
• GLP-2 basal values were significantly higher (GLP-2 promotes epithelial proliferation and barrier integrity)
• Conclusion: "The dietary use of inulin-enriched pasta preserves intestinal mucosal barrier functioning"

Source: https://pubmed.ncbi.nlm.nih.gov/23244539/

Effect of consumption of chicory inulin on bowel function in healthy subjects with constipation: a randomized, double-blind, placebo-controlled trial

Study Type: Randomized, double-blind, placebo-controlled, crossover trial (RCT)

Abstract/Summary: Conducted according to EFSA guidance documents for investigating bowel function. Forty-four healthy volunteers with constipation received either 12g/day chicory inulin (Orafti® Inulin) or maltodextrin placebo for 4 weeks in a crossover design with 2-week washout.

Key Results:

• Stool frequency significantly increased compared to placebo: median 4.0 stools/week vs. 3.0 with placebo (p=0.038)
• Stool consistency improved (softening of stools)
• Trend toward higher satisfaction with bowel function (p=0.059)
• No gastrointestinal discomfort reported
• EFSA Health Claim: The European Food Safety Authority has authorized a health claim stating that 12g/day of 'native chicory inulin' contributes to maintenance of normal defecation

Source: https://www.tandfonline.com/doi/full/10.1080/09637486.2016.1212819

Enhancing gut microbiota and microbial function with inulin supplementation in children with obesity

Study Type: Randomized, double-blinded, placebo-controlled trial (RCT)

Abstract/Summary: This study examined whether inulin supplementation extracted from Thai Jerusalem artichoke improved intestinal microbiota in children with obesity. 165 Thai children with obesity (mean age 10.4±2.2 years) were randomized to receive either inulin supplement extracted from Jerusalem artichoke, maltodextrin placebo, or dietary fiber advice for 6 months. This is the largest RCT documenting gut microbiota changes after prebiotic supplementation in children with obesity.

Key Results:

• Significant increase in alpha-diversity (Shannon Index) in the Jerusalem artichoke inulin group vs. placebo (p=0.028) and dietary fiber advice (p=0.026)
• Alpha-diversity significantly increased from baseline to month 6 only in the inulin group (p=0.033)
• Substantial elevation in Bifidobacterium abundance (p=0.0058 vs. placebo)
• Significant enhancement of butyrate-producing bacteria: Agathobacter, Eubacterium, Subdoligranulum, Blautia, and Megasphaera

Source: https://www.nature.com/articles/s41366-024-01590-8

Inulin supplementation modulates gut microbiota derived metabolites related to brain function in children with obesity

Study Type: Randomized, double-blinded, placebo-controlled trial (RCT)

Abstract/Summary: This study assessed the effects of Jerusalem artichoke inulin supplementation on gut-brain axis (GBA)-related amino acids and bioactive molecules in children with obesity. Children aged 7-15 were randomly assigned to receive inulin supplementation (extracted from Thai Jerusalem artichoke), maltodextrin placebo, or dietary fiber advice for 6 months. This is the largest and first RCT to investigate prebiotic effects on GBA-related molecules in children.

Key Results:

• Inulin supplementation significantly upregulated putrescine over time compared to placebo (p=0.021)
• Putrescine, spermine, and tyrosine (dopamine precursor) showed significant increases from baseline to month 6 exclusively in the inulin group (all p<0.0001)
• Putrescine activates histamine receptors, contributing to regulation of appetite and satiety
• Spermine modulates glutamate receptors and influences neurotransmitter release
• Tyrosine is a dopamine precursor for controlling appetite and energy balance

Source: https://www.nature.com/articles/s41598-025-21079-2

Jerusalem artichoke and chicory inulin in bakery products affect faecal microbiota of healthy volunteers

Study Type: Randomized, double-blind, placebo-controlled, parallel-group trial (RCT)

Abstract/Summary: This study tested the effects of Jerusalem artichoke inulin (JA) in snack bars on composition of faecal microbiota, concentration of faecal SCFA, bowel habit, and gastrointestinal symptoms. Forty-five volunteers participated in a double-blind, randomized, placebo-controlled, parallel-group study with 7-day run-in, 7-day adaptation, and 14-day intervention.

Key Results:

• Slight increase in stool frequency with Jerusalem artichoke inulin consumption
• Stool consistency was positively affected in subjects consuming Jerusalem artichoke snack bars (p<0.05)
• Increased counts of bifidobacteria (+1.2 log10 in 21 days)
• Reduced harmful Clostridium histolyticum/C. lituseburense group

Source: https://pubmed.ncbi.nlm.nih.gov/17445348/

The effects of different dietary fiber pectin structures on the gastrointestinal immune barrier: impact via gut microbiota and direct effects on immune cells

Study Type: Systematic Review

Abstract/Summary: Pectins are dietary fibers with different structural characteristics. Specific pectin structures can influence the gastrointestinal immune barrier by directly interacting with immune cells or by impacting the intestinal microbiota. Due to its gelling ability, pectin can retain water and resist digestive enzymes in the small intestine.

Key Results:

• Pectin forms three-dimensional gel networks through hydrogen bonding and hydrophobic interactions
• The gelation mechanism involves junction zones formed by hydrogen bonds between pectin chains
• In the upper GI tract, pectin is resistant to digestion and hydrolysis, maintaining its gel structure
• Low-methoxyl pectins form gels through calcium ion crossbridging ("egg-box" model)
• High-methoxyl pectins form gels through hydrogen bonds and hydrophobic interactions
• Gel formation increases intestinal viscosity, slowing glucose and lipid absorption
• Mucus Layer Strengthening: Low DM pectins stimulate jejunal mucin secretion; high DM pectins form hydrogen bonds with mucins creating protective gel networks; RG-I pectins preserve goblet cell numbers and Muc-1 expression
• Epithelial Integrity: Pectins maintain tight junction structures (claudin-1, ZO-1, occludin); DM7 pectins preserved tight junctions in mice with pancreatitis; RG-I pectins reduced intestinal permeability by maintaining claudin-1
• Immune Barrier Effects: Pectins interact with TLR2 and TLR4 receptors to modulate immune responses; direct inhibition of pro-inflammatory pathways; interaction with Galectin-3 enhances barrier protection

Source: https://www.nature.com/articles/s12276-020-0449-2

Pectin delays gastric emptying and increases satiety in obese subjects

Study Type: Randomized controlled trial (Human Clinical Trial)

Abstract/Summary: As pectin delays gastric emptying in normal subjects and satiety may be linked to the rate of gastric emptying, this study evaluated, in a group of obese subjects, the effect of adding pectin to a meal on gastric emptying, sensation of satiety, and postprandial plasma cholecystokinin and pancreatic polypeptide levels.

Key Results:

• Study Design: 9 adult obese subjects tested on 2 separate days (randomized crossover)
• Intervention: 15g pectin vs. 15g methylcellulose (control)
• Gastric Emptying Time: t½ = 116 ± 23 min with pectin vs. 71 ± 17 min with control (p<0.001) — a 63% delay
• Satiety Score: 98 ± 7 with pectin vs. 74 ± 17 with control (p<0.001) — a 32% increase
• Conclusion: "As pectin induces satiety and delays gastric emptying in obese patients, it may be a useful adjuvant in the treatment of disorders of overeating"

Source: https://pubmed.ncbi.nlm.nih.gov/3169489/

Efficacy of pectin in the treatment of diarrhea predominant irritable bowel syndrome

Study Type: Randomized controlled trial (Human Clinical Trial)

Abstract/Summary: This study evaluated the efficacy of pectin, a soluble dietary fiber, in diarrhea-predominant irritable bowel syndrome (IBS-D). 87 IBS-D patients were randomized to pectin (n=46) or placebo (n=41) and received 24g pectin powder/day for 6 weeks.

Key Results:

• Pectin significantly alleviated clinical symptoms of IBS-D
• Improved stool frequency and consistency
• Enhanced quality of life scores
• Increased beneficial bifidobacteria populations
• Decreased harmful Clostridium sp. bacteria
• Reduced systemic inflammation
• Conclusion: "Pectin acts as a prebiotic in specifically stimulating gut bifidobacteria in IBS-D patients and is effective in alleviating clinical symptoms, balancing colonic microflora and relieving systemic inflammation"

Source: https://pubmed.ncbi.nlm.nih.gov/25809332/

Dose-dependent effects of apple pectin on alleviating high fat-induced obesity modulated by gut microbiota and SCFAs

Study Type: Controlled dose-response study

Abstract/Summary: This study investigated apple pectin's effects on gut microbiota and SCFA production using standard diet and high fat diet containing 0%, 1%, 3%, 5%, 8%, or 12% apple pectin offered for 8 weeks.

Key Results:

• SCFA Production showed strong dose-response relationships:
  • Acetate: R² = 0.955 correlation with apple pectin dosage
  • Propionate: R² = 0.985 correlation with apple pectin dosage
• Pectin-degrading bacteria increased dose-dependently:
  • Faecalibaculum (R² = 0.963)
  • Ruminococcus (R² = 0.937)
• Attenuation of colonic injury from 5% pectin dosage
• Conclusion: "This study confirmed the dose-sensitive manner of pectin to alleviate HF-induced obesity by modulating gut microbiota and enhancing short-chain fatty acids production"

Source: https://www.sciencedirect.com/science/article/pii/S2213453021000811

Effects of GLP-1 and Its Analogs on Gastric Physiology in Diabetes Mellitus and Obesity

Study Type: Comprehensive Review (with human study data)

Abstract/Summary: This review examines the effects of GLP-1 and its analogs on gastric motor functions. Human studies demonstrate that GLP-1 infusion results in slowing of gastric emptying and increased fasting and postprandial gastric volumes.

Key Results:

• Acute IV administration of GLP-1 slows gastric emptying"profoundly and dose-dependently"
• Effects include: relaxation of the gastric fundus, increased gastric compliance, inhibition of antral contractility, and increased pyloric tone
• Endogenous GLP-1 receptor antagonist (exendin 9-39) accelerated gastric emptying (T50 68±8 min vs. placebo 83±7 min; P<0.001)
• The mechanism is neurally mediated via vagal afferents
• Short-acting GLP-1RAs: delayed gastric emptying is the main mechanism of postprandial glucose suppression

Source: https://pubmed.ncbi.nlm.nih.gov/32077010/

Effects of GLP-1 Analogues and Agonists on the Gut Microbiota: A Systematic Review

Study Type: Systematic Review (38 studies included)

Abstract/Summary: This systematic review gathered evidence on GLP-1 analogue effects on gut microbiota composition, richness, and abundance in both animal and human models.

Key Results:

• Semaglutide treatment: A. muciniphila increased, but microbial diversity decreased
• After 48 weeks of dulaglutide administration, "the composition of the intestinal flora changed significantly, with a significant reduction in the abundance of intestinal flora"
• GLP-1 RAs can reduce gut microbiome diversity and induce dysbiosis through appetite suppression and compromised nutrient intake
• Different GLP-1 analogues showed varying effects on specific bacterial taxa
• Gut microbiota dysbiosis has been shown to cause "GLP-1 resistance" in animal models

Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC12029897/

Rational use of prebiotics for gut microbiota alterations: Specific bacterial phylotypes and related mechanisms

Study Type: Comprehensive Review

Abstract/Summary: This review examined the substrate specificity of prebiotics for gut bacteria. Findings demonstrate that different prebiotics selectively enrich specific bacterial groups at the species or strain level, representing "dietary tuning of colonization by specific groups of gut bacteria."

Key Results:

• Seaweed polysaccharides: specifically enrich certain Bacteroides spp.
• Galacto-oligosaccharides (GOS): specifically enrich certain strains of Bifidobacterium adolescentis
• Inulin-type fructans: selectively stimulate Bifidobacterium and Faecalibacterium prausnitzii
• Arabinoxylan oligosaccharides (AXOS): selectively enriched by B. adolescentis with specific arabinofuranosidase enzymes
• Resistant starch: primarily degraded by Ruminococcus bromii and Bifidobacterium adolescentis
• Different chain lengths affect solubility and bacterial utilization patterns
• XOS: Specifically stimulates Bifidobacterium species
• Pectin: Stimulates Bacteroides, Faecalibacterium, and specific Lachnospiraceae
• Combining prebiotics with different specificities provides complementary coverage of beneficial bacterial populations
• "Different prebiotics may be rationally selected to manipulate specific bacteria in the gut microbiota"

Source: https://www.sciencedirect.com/science/article/pii/S1756464620300621

Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota

Study Type: Comprehensive Review

Abstract/Summary: This review provides an overview of SCFA-producing bacteria, their biochemical processes, and the distinct metabolites they produce. Different bacterial taxa produce specific SCFAs through different metabolic pathways, and these metabolites serve distinct physiological functions.

Key Results:

• Acetate (60% of total SCFAs): Produced primarily by Bifidobacteria through acetogenesis pathways
• Propionate (20%): Produced via three distinct pathways by Bacteroidetes, Negativicutes, Coprococcus spp., Roseburia inulinivorans, and Blautia species
• Butyrate (20%): Produced by Firmicutes—Lachnospiraceae (Roseburia, Eubacterium hallii) and Ruminococcaceae (Faecalibacterium prausnitzii)
• Distinct functions:
  • Butyrate: Primary energy source for colonocytes, enhances gut barrier, anti-inflammatory
  • Propionate: Regulates hepatic gluconeogenesis, reduces cholesterol synthesis
  • Acetate: Regulates appetite via GLP-1 and PYY secretion, crosses blood-brain barrier

Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC10180739/

Increasing the diversity of dietary fibers in a daily-consumed bread modifies gut microbiota composition and function

Study Type: Double-blind, randomized, cross-over study (n=39)

Abstract/Summary: This study tested whether a 7-dietary fiber mixture (increased diversity) would improve gut microbiota compared to standard bread in subjects at cardiometabolic risk. Subjects consumed 150g of standard bread (5.55g fiber) or enriched bread with 7-fiber mixture (16.05g fiber) for 8 weeks each.

Key Results:

• Increasing fiber diversity modified gut microbiota composition and promoted glycoside hydrolase families involved in plant polysaccharide degradation
• Higher fiber diversity was associated with improved cardiometabolic markers (lipid profile, insulin sensitivity)
• Conclusion: "Increasing the diversity of dietary fibers in a daily consumed product modifies gut microbiota composition and function and could be a relevant nutritional tool to improve cardiometabolic profile"

Source: https://www.tandfonline.com/doi/full/10.1080/19490976.2022.2044722

Dynamics of Human Gut Microbiota and Short-Chain Fatty Acids in Response to Dietary Interventions with Three Fermentable Fibers

Study Type: Randomized crossover trial (Human Clinical Trial)

Abstract/Summary: This study investigated how different fermentable fibers (inulin, arabinoxylan, and resistant starch) affect gut microbiota and SCFA production in different regions of the digestive tract. Healthy adults consumed each fiber for 1 week with washout periods.

Key Results:

• Different fibers were fermented in different locations along the digestive tract
• Inulin was primarily fermented in the proximal colon
• Arabinoxylan showed fermentation throughout the colon
• Each fiber enriched distinct bacterial populations and produced different SCFA profiles
• Combining multiple fiber types provides broader coverage of the digestive tract

Source: https://journals.asm.org/doi/10.1128/mbio.02566-18

Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial

Study Type: Double-blind, randomized, placebo-controlled trial (n=250)

Abstract/Summary: This RCT evaluated the effects of four prebiotic/probiotic formulas (polydextrose, psyllium husk, wheat bran + psyllium husk, probiotic combination) versus placebo on functional constipation symptoms over 4 weeks.

Key Results:

• All fiber intervention groups showed mean increases in Bristol Stool Scale of 0.95-1.05 compared to baseline (indicating softer, more comfortable stools)
• Daily intake of 5g psyllium husk was sufficient to relieve hard stool
• Dietary fiber interventions modulated gut microbiota composition and improved constipation symptoms
• Anaerostipes genus changes were positively correlated with bowel movement frequency improvement

Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC10120550/

References:

1. https://www.mdpi.com/2076-2607/13/9/2068
2. https://pmc.ncbi.nlm.nih.gov/articles/PMC9293236/
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC11407914/
4. https://pubs.rsc.org/en/content/articlehtml/2014/fo/c3fo60348b
5. https://pmc.ncbi.nlm.nih.gov/articles/PMC4528259/
6. https://pubmed.ncbi.nlm.nih.gov/24661576/
7. https://www.nature.com/articles/s41522-024-00533-5
8. https://pubmed.ncbi.nlm.nih.gov/23244539/
9. https://www.tandfonline.com/doi/full/10.1080/09637486.2016.1212819
10. https://www.nature.com/articles/s41366-024-01590-8
11. https://www.nature.com/articles/s41598-025-21079-2
12. https://pubmed.ncbi.nlm.nih.gov/17445348/
13. https://www.nature.com/articles/s12276-020-0449-2
14. https://pubmed.ncbi.nlm.nih.gov/3169489/
15. https://pubmed.ncbi.nlm.nih.gov/25809332/
16. https://www.sciencedirect.com/science/article/pii/S2213453021000811
17. https://pubmed.ncbi.nlm.nih.gov/32077010/
18. https://pmc.ncbi.nlm.nih.gov/articles/PMC12029897/
19. https://www.sciencedirect.com/science/article/pii/S1756464620300621
20. https://pmc.ncbi.nlm.nih.gov/articles/PMC10180739/
21. https://www.tandfonline.com/doi/full/10.1080/19490976.2022.2044722
22. https://journals.asm.org/doi/10.1128/mbio.02566-18
23. https://pmc.ncbi.nlm.nih.gov/articles/PMC10120550/