Prebiotic Spotlight: Prebiotics and Digestive Complaints

Each edition of GPA’s Prebiotic Spotlight focuses on a specific prebiotic type to raise awareness around the prebiotic itself, its sources, any notable and/or recent research, and how it is used in the marketplace. This edition takes a new approach by reviewing the literature to identify health complaints associated with prebiotic consumption, with a particular focus on digestive complaints.

Overview

Prebiotics contain polymeric bonds that humans lack the enzymes to hydrolyze, allowing prebiotics to reach the colon intact, where they are fermented by beneficial gut bacteria such as Lactobacilli and Bifidobacteria. This fermentation produces by-products such as short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate which exert various anti-inflammatory and immunomodulatory effects (Guarino et al., 2020). While prebiotic research demonstrates health benefits attributed to SCFAs production, misconceptions persist that all prebiotics cause gastrointestinal complaints. In reality, prebiotics vary in physiochemical structures, degree of polymerization, and dosages, which influence gastrointestinal tolerance. Accordingly, prebiotic intake may be associated with gastrointestinal-related adverse events depending on these factors (Li et al., 2025). This report discusses the mechanisms, dose-response relationships, and tolerance associated with prebiotic supplementation.

Factors Influencing Gastrointestinal Side Effects of Prebiotics

Several factors can influence the occurrence of gastrointestinal side effects associated with prebiotic intake, including timing of intake and fluid consumption, prebiotic type and dosage, and degree of polymerization. An understanding of these variables is important for optimizing tolerability and minimizing adverse gastrointestinal effects. Each of these factors are discussed below.

a) Timing of Intake and Intake of Fluids

While prebiotics are generally well tolerated and cause minimal gastrointestinal discomfort when consumed gradually, they have been associated with mild and temporary gastrointestinal complaints, such as bloating, flatulence, cramps, and loose stools (Guarino et al., 2020; Gonçalves et al., 2022). These symptoms especially tend to occur at the initial phases of prebiotic intake. Valcheva et al. (2019) reported an increase in bloating and flatulence 48 to 72 hours after prebiotic intake, specifically after the consumption of high doses of β-fructans. Nonetheless, it was noted that effects were transient and improved over the course of the intervention, suggesting an adaptation of the gut over time (Valcheva et al., 2019). Similarly, the timing of prebiotic intake may also play a role in influencing gastrointestinal side effects.

For example, the consumption of prebiotics prior to a meal may increase the likelihood of experiencing gastrointestinal adverse effects such as bloating, although further research is needed to confirm this link (Tandon et al., 2019). Regarding fluid intake, a study by Gonçalves et al. (2022) suggested that increasing daily water intake from 538 to 1990 mL, alongside higher dietary fiber supplementation with a blend of fibers including wheat bran, pectin, and green banana flour (13 g/day for women and 20 g/day for men), may enhance intestinal adaptation to fiber, support beneficial shifts in the gut microbiota, and consequently reduce transient gastrointestinal symptoms compared to fiber intake alone. Collectively, gastrointestinal side effects associated with prebiotic intake are influenced by factors such as timing of intake and hydration status, with symptoms typically diminishing over time as the gut adapts.

b) Prebiotic Type and Dosage

Certain prebiotics, specifically when consumed at higher doses, tend to increase the likelihood of gastrointestinal side effects. For example, human milk oligosaccharides (HMOs), especially 2-O-fucosyllactose (2’FL) and lacto-N-neotraose (LNnT), may increase the likelihood of gastrointestinal side effects such as bloating and flatulence at a dose of 20 g; however, supplementation at 5 g and 10 g was found to be safe and well tolerated in adults (Elison et al., 2016). Li et al. (2025) evaluated supplementation with 15 g of FOS or inulin over 4 weeks, where participants were instructed to begin consumption with half the dose for the first two days to adapt to the prebiotic and minimize gastrointestinal symptoms. Additionally, different prebiotic types may elicit different gastrointestinal side effects due to varying microbiota fermentation patterns. To expand, an in vitro fermentation study assessed the effects of three different prebiotics: HMOs (2’-FL), FOS, and GOS formulated as a mixture and administered to patients with ulcerative colitis. All three prebiotics increased the levels of short chain fatty acids (SCFAs), whereas 2’-FL produced the greatest increase in total SCFA and acetate levels (Kennedy et al., 2024). Overall, gastrointestinal side effects associated with prebiotic intake are influenced by factors like prebiotic dosage and type, where higher doses and fermentability patterns of certain prebiotics contributing to greater side effects.

c) Degree of Polymerization

The degree of polymerization (DP) is the number of monomer units in a polymer chain, and is a key structural characteristic of prebiotics. It affects their physical properties, the composition of fermenting gut microbiota, and their associated health benefits (Chen et al., 2020). As such, DP influences both the severity and nature of gastrointestinal adverse effects that may be experienced with prebiotic intake. Fructans, such as inulin and FOS, are composed of fructose units that differ in chain length and DP, resulting in variable physiological effects experienced with different fructans (Kolida et al., 2002; Li et al., 2025). For instance, inulin has a longer chain and as a result, tend to cause more pronounced gastrointestinal side effects compared to short chain prebiotic fibers like FOS, which are more rapidly fermented and generally produce milder side effects (Calame et al., 2008; Guarino et al., 2020; JanssenDuijghuijsen et al., 2024; Wilson et al., 2019). Interestingly, FOS have been shown to be well tolerated at doses up to 40 g/day

producing only mild clinical symptoms such as bloating, borborygmi, flatulence, and abdominal pain (Le Bourgot et al., 2022). Similarly, an in vitro study by Chen et al. (2020) assessed the relationship between three prebiotic fibers with different DP, including carboxymethylcellulose, β-glucans, and GOS on the human gut microbiota. The study found that butyric acid concentration declines with decreasing DP, while specific operational taxonomic units are associated with DP as some taxa increase while others decrease with variable chain length. Altogether, gastrointestinal side effects linked to prebiotic consumption may be influenced by the DP of the prebiotic fibers, with evidence suggesting that shorter chains are generally better tolerable than long chains. Nonetheless, additional research remains needed to confirm these findings.

Mechanisms of Prebiotic-Induced Gastrointestinal Effects

The human colon lacks the enzymes required to metabolize polymer bonds present in prebiotics. As a result, prebiotics are fermented and metabolized by the gut microbiota, leading to the production of SCFAs and gas as byproducts (Guarino et al., 2020). While SCFAs confer important gut health benefits, gas production and increased osmotic pressure can stimulate peristalsis, potentially leading to gastrointestinal side effects such as bloating, flatulence, and diarrhea (Guarino et al., 2020). Supporting this, a meta-analysis and systematic review reported flatulence and bloating in 7 out of 17 studies evaluating FOS consumption (Zheng et al., 2024). Additionally, participants receiving 14 g/day of resistant dextrin reported increased sensations of flatulence at initial administration, which decreased during treatment and decreased further during the post-administration phase, suggesting the adaptive gut-microbiota response to prebiotic fibers (Barber et al., 2022). Similarly, Bush & Alfa (2024) conducted a post hoc analysis of a randomized controlled trial (RCT) to evaluate the effects of 3.5 g and 7 g of resistant potato starch (RPS) on gut microbiota and abdominal symptoms. For example, changes in belching were positively correlated with changes in Papillibacter and Enterobacteriaceae in those supplementing with 7 g and 3.5 g RPS, respectively. In addition, changes in bloating were positively correlated with changes in several bacteria, including Lachnospira and Granulicatella, in participants supplementing with 7 g RPS. Overall, RPS supplementation did not significantly affect mean abnormal bowel symptom scores or mean relative abundance of these taxa. To conclude, gastrointestinal side effects linked to prebiotic consumption may result from mechanisms such as the production of fermentation byproducts, adaptation of the gut microbiota, and changes in gut osmotic activity (Guarino et al., 2020; LeFranc-Millot et al., 2012; Yu et al., 2020).

Prebiotic Intake and Gastrointestinal Symptoms: A Dose-Response Relationship

Several human studies have demonstrated dose-response relationships with prebiotic supplementation, suggesting that the prebiotic dose directly influences the severity of gastrointestinal effects. A meta-analysis by Wilson et al. (2019) suggested that prebiotics improve flatulence when consumed at quantities lower than 6 g/day, while higher doses may exacerbate it (Wilson et al., 2019). For example, supplementation with a galactose-based

prebiotic such as β-GOS (Bimuno®) at a dose of 2.75 g/day in subjects with gastrointestinal symptoms resulted in reduced bloating, flatulence, and abdominal pain, suggesting its potential for managing these symptoms (Vulevic et al., 2018). Similarly, a meta-analysis by De Vries et al. (2019) examined prebiotic tolerance, finding that β-fructans consumption at 10-12 g/day did not induce significant gastrointestinal symptoms, even in subjects with prior gastrointestinal complaints or hypersensitive irritable bowel syndrome (IBS). Instead, regular intake of β-fructans was associated with symptom improvement. However, with occasional intake, doses exceeding 10-12 g/day increased the likelihood of minimal and transient gastrointestinal symptoms (De Vries et al., 2019). Comparably, a study found that the consumption of partially hydrolyzed guar gum (PHGG) at a dose of 6 g/day for 12 weeks improved gastrointestinal symptoms such as bloating and gas compared to placebo in patients with IBS. Nonetheless, the study reported that nine participants who received PHGG experienced mild adverse effects including abdominal pain, nausea, diarrhea, heartburn, and gas, although it was unclear whether these events were related to PHGG administration or IBS (Niv et al., 2016). Additionally, a study by Akçali et al. (2025) reported that in patients with constipation predominant IBS, supplementation with an inulin/oligofructose mixture (50:50 mixture, 9.2 g daily) for eight weeks resulted in a significant increase in IBS Quality of Life Scale and a reduction in total IBS-Symptom Severity Score Scale. Improvements were particularly noted for abdominal pain, bloating, and dissatisfaction with defecation habits. The intervention also significantly improved the IBS-Visual Analogue Scale parameters for constipation status and psychological state, and no adverse events were reported. Furthermore, a study in overweight and prediabetic patients receiving 45 g of resistant starch (RS) type 2 reported potential intervention-related adverse events, including flatulence, headaches, bloating, heartburn, nausea, cramps, diarrhea, indigestion, and swelling. Notably, these events occurred in both the intervention and control groups, with the control group reporting more cases of constipation than the RS group (Peterson et al., 2018). Strikingly, the evidence is inconclusive regarding the dose-response relationships with prebiotic supplementation, even for the same prebiotic. For example, a meta-analysis of RCTs by Dou et al. (2022) found that FOS supplementation, while modulated the gut microbiota in a dose-response and length of intake dependent manner, was not associated with a dose-response relationship for gastrointestinal symptoms. As such, these findings suggest that while certain prebiotics show a clear dose-response effect, with higher doses more likely to elicit gastrointestinal effects, other prebiotics, such as FOS, may not follow this pattern.

Tolerance of Prebiotic Supplementation

Although gastrointestinal side effects are relatively common with prebiotic consumption, the evidence indicates that many prebiotic types are generally well tolerated. The list below highlights their tolerability across diverse populations.

• • Supplementation with 15 g of inulin or FOS was well tolerated, with no serious adverse events reported compared to placebo in a 4-week RCT involving overweight/obese and healthy adults (Li et al., 2025).
  • Infant formulas supplemented with oligosaccharides, including FOS/GOS up to 8 g/L or HMOs up to 3 g/L are generally safe and well tolerated (Kadim et al., 2025; Leong et al., 2025).
  • GOS is generally well tolerated at approximately 2 g/day (3 capsules, twice daily; 333.3 mg GOS per capsule) in adults with functional constipation. No significant adverse effects were reported, aside from a significantly decreased pulse rate (Lee et al., 2024).
  • HMOs show no safety or tolerability concerns in infants, children, and adults. Daily bolus intake of up to 20 g in adults may lead to mild adverse events, but this exceeds typical real-life doses (Schönknecht et al., 2023).
  • Supplementation with 11 g/day of GOS for three weeks in middle-aged adults with self-reported constipation tended to increase stool frequency and significantly increased the abundance of Anaerostipes hadrus, with no significant adverse events reported (Schoemaker et al., 2022).
  • RS type 2 supplementation at doses of 20-40 g/day has been shown to be safe and well tolerated (Sobh et al., 2022).
  • Xylo-oligosaccharides at 1.4 and 2.8 g/day were well tolerated over 8-week administration, without gastrointestinal side effects reported (Finegold et al., 2014; Guarino et al., 2020).
  • Resistant dextrin (NUTRIOSE®) is well tolerated when consumed for 14 days, with higher doses of 10 and 20 g/day leading to flatulence, which was more frequent but milder than placebo (LeFranc Millot et al., 2012).

Conclusion

In summary, prebiotics are generally safe, well tolerated, and associated with various health benefits, although mild gastrointestinal symptoms may occur, particularly during initial intake. Factors such as dose, prebiotic type, DP, fluid intake, and timing of consumption may influence tolerability. As such, gradual dose escalation and adequate fluid intake are recommended to minimize transient gastrointestinal discomfort. Overall, the evidence supports the use of prebiotics across populations and age groups, while emphasizing the need for further research to optimize personalized dosing strategies and prebiotic selection.