Prebiotics and SCFA Alleviate Parkinson’s-Related Constipation: Results from a Randomized Controlled Trial

Tobias Hegelmaier; Alexander Duscha; Christiane Desel; Lisa-Marie Würtele; Jana Peplinski; Diana Jauk; Riccardo Troisi; Martin Klietz; Simon Faissner; Thomas Müller; Aiden Haghikia

doi:10.1007/s40120-026-00972-6

. 2026 Jun 18;15(4):2027–2040. doi: 10.1007/s40120-026-00972-6

Prebiotics and SCFA Alleviate Parkinson’s-Related Constipation: Results from a Randomized Controlled Trial

Tobias Hegelmaier ^1,^#, Alexander Duscha ^1,^#, Christiane Desel ^1,^#, Lisa-Marie Würtele ², Jana Peplinski ², Diana Jauk ², Riccardo Troisi ¹, Martin Klietz ¹, Simon Faissner ², Thomas Müller ³, Aiden Haghikia ^1,^✉,^#

PMCID: PMC13396302 PMID: 42315784

Abstract

Introduction

Constipation is a prevalent and clinically significant non-motor symptom in Parkinson’s disease (PD), affecting up to 90% of patients and often preceding motor dysfunction by several years. Imbalance in the gut microbiota and reduced short-chain fatty acid (SCFA) production potentially contribute to PD pathogenesis and symptom onset. This study aimed to determine whether supplementation with SCFAs, the prebiotic 2-fucosyllactose (2-FL), or their combination alleviates constipation and improves the quality of life of individuals with PD.

Methods

In a double-blind, randomized, parallel-group clinical trial, 72 patients with PD were assigned to either SCFA, 2-FL, or combined supplementation groups for 6 months. Constipation and quality of life were assessed using the Cleveland Clinic Constipation Score, Bristol Stool Scale, and Patient Assessment of Constipation–Quality of Life, alongside routine neurological evaluation and physical activity questionnaires.

Results

2-FL and combined supplementation significantly reduced constipation severity after 6 months, with the combination yielding the most pronounced and sustained benefits concerning stool consistency, defecation frequency, and patient-reported outcomes. Physical activity remained unchanged and did not affect constipation-related outcomes.

Conclusion

Combined prebiotic and SCFA supplementation effectively alleviate constipation symptoms in patients with PD and improves patient quality of life. Future research should assess the long-term implications and potential disease-modifying effects.

Trial Registry

The study was retrospectively registered with the German Clinical Trials Register (DRKS) under the identifier DRKS00027061 on 19 November 2021 (https://drks.de/search/en/trial/DRKS00027061/details).

Supplementary Information

The online version contains supplementary material available at 10.1007/s40120-026-00972-6.

Keywords: Gastrointestinal symptoms, Metabolites, Microbiota, Parkinson’s disease, Prebiotics, Short-chain fatty acids

Plain Language Summary

Many people with Parkinson’s disease experience constipation, which can be distressing and greatly affect daily life. Constipation may appear years before movement problems and is thought to be linked to changes in gut bacteria and reduced production of beneficial substances called short-chain fatty acids. In this clinical study, we investigated whether dietary supplementation with short-chain fatty acids, the prebiotic 2-fucosyllactose, or a combination of both could improve constipation in people with Parkinson’s disease, and 72 participants received one of these supplements for 6 months. We found that supplementation with 2-fucosyllactose improved constipation symptoms, while the combination of 2-fucosyllactose and short-chain fatty acids led to the greatest and most consistent improvements, with participants reporting better stool consistency, fewer problematic bowel movements, and an improved constipation-related quality of life. Physical activity levels did not change during the study, indicating that the observed benefits were likely related to the supplements themselves. These findings suggest that targeting the gut using specific dietary supplements may offer a safe and effective way to relieve constipation in people with Parkinson’s disease, although further studies are needed to evaluate the long-term safety of these supplements, the sustainability of symptom relief, the long-term benefits, and possible effects on disease progression.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40120-026-00972-6.

Key Summary Points

Why carry out this study?

Constipation affects up to 80–90% of patients with Parkinson’s disease and represents a clinically relevant non-motor symptom with substantial impact on quality of life and disease burden.

This study assessed whether supplementation with short-chain fatty acids (SCFAs), the prebiotic 2-fucosyllactose (2-FL), or their combination alleviates constipation and improves quality of life in patients with Parkinson’s disease.

What was learned from the study?

Combined supplementation with 2-FL + SCFA significantly reduced constipation severity and improved stool consistency, defecation patterns, and patient-reported outcomes over 6 months, with greater effects than single interventions.

These findings suggest a synergistic therapeutic effect and support microbiome-directed dietary interventions as a potential safe adjunctive strategy for managing gastrointestinal symptoms in Parkinson’s disease, warranting further investigation of long-term and disease-modifying effects.

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Introduction

Parkinson’s disease (PD) is one of the most prevalent neurodegenerative disorders worldwide, characterized by not only motor symptoms but also a wide range of non-motor symptoms, which can often precede the onset of motor symptoms by decades. Among the various gastrointestinal (GI) symptoms reported, constipation is remarkably prevalent, affecting 80–90% of patients. Other manifestations, such as drooling, dysphagia, and small intestinal bacterial overgrowth (SIBO), are also frequently encountered and contribute significantly to the non-motor symptom burden in PD [1, 2]. Risk determinants for PD include not only genetic influences but also a range of environmental factors, notably dietary patterns and gut health [3]. The intestinal microbiota has been increasingly recognized to play a significant role in human health and disease, including PD [4]. Changes in microbial composition can augment local and neuroinflammation through several mechanisms, including disruption of intestinal barrier integrity. Along with a well-documented dysbiosis in PD, decreased relative abundance of putative anti-inflammatory, short-chain fatty acid (SCFA)-producing bacteria, and thus reduced levels of SCFA such as propionate (PA) and butyrate (BA) within the gut, have been reported [5, 6]. SCFA serve as immune modulatory metabolites and are critical in maintaining intestinal barrier integrity [7–9]. In addition to modulating the course of PD, dysbiosis and local inflammation can also promote constipation [10]. Studies on the effects of probiotics on PD-related motor and non-motor symptoms, as well as inflammatory factors, have produced inconsistent results [11–15]. One study found that administering complex probiotics improves motor symptoms [14] while other trials and systematic reviews found no measurable improvement in motor function or systemic inflammation following probiotic supplementation [13, 15]. Consumption of prebiotic fibers influences microbiota composition and levels of SCFA and have recently been found to improve GI symptoms in PD [16, 17]. The prebiotic 2-FL has been associated with beneficial effects in patients with irritable bowel syndrome (IBS) and ulcerative colitis, as it may alleviate both intra- and extraintestinal symptoms [18]. Recently, we demonstrated a positive effect of 2-FL and SCFA on motor symptoms after a 6-month supplementation [19]. The influence of direct supplementation of SCFA and 2-FL on constipation in patients with PD has not yet been investigated.

In this study, we investigated the influence of supplementation with the SCFAs BA and PA, the prebiotic 2-FL, and their combination on constipation in 72 patients with PD. Constipation was evaluated as an exploratory endpoint in order to assess potential GI benefits associated with these interventions.

Methods

Study Design and Participants

This parallel, double-blind, randomized trial was performed from November 2019 to August 2020. All participants provided informed consent prior to participation. This clinical trial was retrospectively registered in the German Clinical Trials Register (DRKS; registration number DRKS00027061) because registration was completed after enrollment had begun due to administrative delay (https://drks.de/search/en/trial/DRKS00027061/details). A total of 94 individuals were assessed for their suitability, and 72 patients were ultimately enrolled and randomly allocated to a single treatment group. We reference the CONSORT diagram as described by Hegelmaier et al. (Table 1) [19]. Exploratory sex-specific analyses were additionally performed in male participants, whose baseline demographic and clinical characteristics are summarized in Supplementary Table 1. Inclusion criteria were between 18 and 90 years of age, diagnosis of a primary Parkinsonian syndrome with a moderate disease severity, and full orientation of the study participants. Exclusion criteria were immunosuppressive therapy within the past 6 months, the use of antibiotics or metformin in the past 3 months, and strict vegan dietary habits. Participants were required to maintain a stable dosage of any concomitant medications and PD-related therapies, throughout the 6-month study period. In addition, no participant used laxatives or other medications affecting bowel habits at baseline, and the use of such agents was not permitted during the study period. Compliance with this restriction was assessed at each study visit (baseline, 3 months, and 6 months), with no reported use throughout the study. Participants underwent routine evaluations at an outpatient clinic every 3 months following the initiation of supplementation, during which a neurologist conducted a comprehensive neurological examination. The side effects were generally mild, with only one participant dropping out of the study. The reported adverse events included gastrointestinal discomfort and mild bloating.

Table 1.

Demographic data and characteristics of all three intervention groups

Characteristics	SCFA (n = 24)	2-FL (n = 23)	SCFA + 2-FL (n = 24)	p
Female sex, n (%)	13 (54.2%)	8 (34.8%)	13 (54.2%)	0.31^a
Age, years, mean ± SD	66.2 (± 11.09)	62.83 (± 9.68)	64.5 (± 9.6)	0.53^b
Duration of disease, years, mean ± SD	6.42 (± 5.56)	6.17 (± 5.77)	4.58 (± 4.46)	0.43^b
BMI	25.42 (± 2.82)	24.85 (± 3.32)	26 (± 2.76)	0.93^b
Subgroups				0.55^a
Non-tremor phenotypes	22 (91.7%)	20 (87%)	23 (95.8%)
Tremor-dominant phenotype	2 (8.3%)	3 (13%)	1 (4.2%)
Medication
l-Dopa (mg) daily dose	770 (± 302)	788 (± 272)	756 (± 261)	0.92^b
Benserazide	24 (33.8%)	22 (30.99%)	22 (30.9%)	0.33^a
Carbidopa	2 (37%)	6 (8.45%)	3 (4.23%)	0.22^a
Piribedile	0	3 (13%)	1 (4.2%)	0.14^a
Rotigotine	2 (8.7%)	2 (8.7%)	3 (12.5%)	0.89^a
Ropinirole	2 (8.7%)	1 (4.3%)	2 (8.3%)	0.83^a
Pramipexole	2 (8.7%)	4 (17.4%)	4 (16.7%)	0.61^a
Rasagiline	12 (52.2%)	11 (47.8%)	12 (50%)	0.99^a
Selegiline	4 (17.4%)	5 (21.7%)	5 (20.8%)	0.99^a
Safinamide/Xadago	1 (4.3%)	3 (13%)	1 (4.2%)	0.59^a
Opicapone	6 (25%)	8 (34.8%)	9 (37.5%)	0.62^a
Amantadine	2 (2.82%)	2 (2.82%)	1 (1.41%)	0.8^a
Apomorphine	0	0	0	–
Anticholinergics	0	0	1 (1.41%)	0.37^a
Clozapine	2 (8.7%)	0	1 (4.2%)	0.37^a
Quetiapine	3 (13%)	0	2 (8.3%)	0.24^a
MDS-UPDRS III	29.2 (± 16.78)	34 (± 16.14)	29.9 (± 16.4)	0.57^b
Hoehn and Yahr	2.2 (± 0.72)	2.2 (± 0.67)	2.3 (± 0.95)	0.99^c

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Modified according to Hegelmaier et al. [19]. No participant had used laxatives or other agents affecting gut motility or bowel habits prior to study enrollment, including prokinetic or secretagogue therapies such as prucalopride, linaclotide, lubiprostone, or plecanatide. Participants were also not receiving these medications at baseline

n number, SD standard deviation, BMI body mass index, MDS-UPDRS III Movement Disorders Society-Unified Parkinson’s Disease Rating Scale, motor part

^aChi-squared test

^bAnalysis of variance (ANOVA)

^cKruskal–Wallis test

This study presents the exploratory secondary clinical endpoints concerning gastrointestinal symptoms and quality of life from the same cohort previously described by Hegelmaier et al. (Table 1) [19]. In the main study, the primary endpoints were changes in gut microbiome diversity and composition as well as SCFA concentrations in stool and serum following 6 months of supplementation. In the primary endpoint analyses, supplementation did not significantly alter gut microbiome diversity or overall composition, while fecal SCFA concentrations remained unchanged and serum butyrate and propionate levels showed a slight increase after treatment. The primary endpoint was the diversity and composition of the microbiome, and as a result of the early-phase nature of the study, we did not include a control arm. The trial was designed as a comparative study to evaluate the relative efficacy of three active microbiome-modulating interventions. The decision to omit a placebo arm was based on the study’s primary objective—characterizing the differential impacts of SCFAs, 2-FL, and their combination on microbial composition—and the prioritization of active-treatment comparisons to identify the most effective therapeutic candidate for future investigation.

Ethical Approval

The study was approved by the Ethics Committee of the Ruhr-University Bochum (approval number 19-6713). This study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments, with the exception that this trial was retrospectively registered. All participants provided written informed consent prior to inclusion in the study.

Randomization and Masking

Randomization and blinding procedures followed the methodology described in Hegelmaier et al. [19]. Briefly, participants were randomly assigned (1:1:1) to one of three study arms using permuted block randomization with allocation concealment and blinding of patients and investigators. To ensure the integrity of the double-blind design, participants in all three arms received an identical number of supplements. Those assigned to the single-intervention groups (SCFA or 2-FL) received a matching placebo for the alternate substance. All active supplements and placebos were identical in appearance, weight, and packaging, making the treatment regimens indistinguishable to both participants and investigators. Allocation was performed by an independent third party not involved in the clinical assessments, and blinding was maintained until the 6-month study period had concluded and the final dataset was locked for analysis.

Cleveland Clinic Constipation Score (CCCS)

To investigate constipation-related symptoms, we used the Cleveland Clinic Constipation Score (CCCS), also described as the Wexner questionnaire [20], which objectively rates the severity of constipation. It consists of eight items evaluating key constipation-related symptoms, specifically the frequency of bowel movements, abdominal pain, time per defecation event, or incomplete evacuation. Each item is typically scored from 0 to 4 points with increasing severity of symptoms, except for assistance during defecation, which is scored between 0 and 2. Possible additive scores range between 0 (normal defecation, no symptoms) and 30 (severe constipation), where a score of 15 and above was associated with clinically significant constipation in several studies and cross-cultural adaptations [20–23].

Bristol Stool Scale (BSS) and Defecation Frequencies

Stool consistency, together with the frequency of defecation as potential evidence for constipation, was evaluated using the Bristol Stool Scale (BSS) questionnaire, which includes verbal as well as visual classification of fecal consistency of the last defecation on a 7-point scale [24]. Items range from hard and lumpy consistencies (1 + 2), sausage-shaped (3 + 4), to more soft, mushy, or watery consistencies. Types 1 and 2 are generally associated with constipation, whereas types 6 and 7 are classified as diarrhea. Both scale edges are associated with functional bowel disorders, such as irritable bowel diseases (IBD) [25, 26]. Types 3–5 are considered normal/healthy stool types. Frequencies were determined as the number of defecations per day. Individual BSS results and defecation frequencies were grouped according to the treatment regimen and study time point and were subsequently analyzed.

Patient Assessment of Constipation–Quality of Life (PAC-QOL)

The impact of constipation on individual patients’ quality of life was assessed using the PAC-QOL [27]. This questionnaire was validated in various studies investigating quality of life related to opioid-induced constipation in patients with cancer or postoperative constipation [28, 29]. It consists of 28 items, which are distributed among four major subscales, namely physical discomfort, psychosocial discomfort, worries and concerns, and satisfaction, and recapitulates an observational period of 2 weeks before the visit. Each item has a possible score ranging from 0 (no impact) to 5 (heavy impact) of the associated factors on the patients’ lives. For statistical analysis, we calculated the mean of overall scores per individual at baseline, after 3 months, and after 6 months and performed subsequent intergroup analyses.

Simple Physical Activity Questionnaire (SIMPAQ)

To assess daily individual physical activity, the SIMPAQ questionnaire was used because of its easy-to-answer structure, which is based on a five-item interview regarding physical activity in the last 7 days. The SIMPAQ was originally developed as a measuring tool to investigate physical activity in patients with psychiatric disorders such as schizophrenia and depression [30, 31], as patients displayed divergent results during test–retest reliability studies with the frequently used International Physical Activity Questionnaire (IPAQ). SIMPAQ consists of different textboxes, one asking for the time spent in bed (i.e., total hours lying in bed including sleeping time and resting), one for sedentary time including napping, one for the walking time during the previous week, one for time spent on exercises and one for time spent for incidental activity [30]. Activity was noted in minutes per week for all boxes and activity time was calculated based on individual patient reports afterwards for subsequent analysis per treatment group.

Results

Constipation-Related Symptoms Decreased During 6 Months of Prebiotic and SCFA Supplementation

Evaluation of the CCCS questionnaires showed no differences between groups at baseline, in which all patients showed a moderate level of constipation-related symptoms, regardless of their group assignment. Supplementation with 2-FL significantly reduced symptom burden over 6 months compared to baseline, whereas SCFA supplementation showed only a trend towards a decrease in CCCS over the study period. However, combined supplementation with 2-FL and SCFA showed significant improvement in symptoms after 3 months compared to baseline, which was even more pronounced after 6 months of consecutive 2-FL + SCFA intake (Fig. 1).

Fig. 1 — Constipation-related symptoms decreased during supplementation with 2-FL and combined treatment with 2-FL and SCFAs in patients with PD. Gray lines display individual patient scores at all study time points; black lines show mean ± SEM. 3-month (V1) and 6-month (V2) clinical evaluations. Scores from all Cleveland Clinic Constipation Score (CCCS) items were added up per patient in each group and differences between time points within groups were statistically analyzed by two-way analysis of variance (ANOVA) in combination with Tukey’s test for multiple comparisons after verification of normal data distribution; 2-FL n = 23, SCFA n = 24, 2-FL + SCFA n = 24; *p < 0.05, **p < 0.01, ***p < 0.001

Stool Form and Defecation Frequency Improved During Prebiotic and SCFA Supplementation

To investigate the causality between decreased constipation-related symptoms and possible improvements in bowel movement as indicated by stool consistency, we evaluated the BSS in combination with defecation frequencies. Here we saw that baseline stool form in all three groups did not differ and showed associations with constipation. During 3 and 6 months of supplementation, stool form significantly transitioned towards a more typical, healthy direction only in the combined supplementation group. We could not detect significant changes in both single-supplementation groups, although a trend in fecal consistency improvement could be observed in the SCFA supplementation group (Fig. 2a). In line with these results, defecation frequency also decreased significantly in the combined supplementation group over the study period from 2 to 1 attempt per day. Interestingly, a significant decrease over 6 months was also detectable in the 2-FL supplementation, while the SCFA group only displayed a tendency for decreased defecation attempts per day (Fig. 2b).

Fig. 2 — Stool form and evacuation attempts were significantly reduced during supplementation of 2-FL in combination with SCFA. 3-month (V1) and 6-month (V2) clinical evaluations. a Consistency and form of the last defecation before the visit shows significant improvement of pathological constipation-related stool form during 6 months of supplementation with 2-FL and SCFA. Bristol Stool Scale (BSS) b Defecation attempts were significantly reduced in the 2-FL supplementation group after 6 months and more prominent in the combined supplementation group, where attempts per day were halved after 3 months and 6 months of supplementation, respectively. Questionnaire results were displayed as individual values, while bar graphs show mean ± SEM. Differences between time points within groups were statistically analyzed by two-way analysis of variance (ANOVA) in combination with Tukey’s test for multiple comparisons after verification of normal data distribution; 2-FL n = 23, SCFA n = 24, 2-FL + SCFA n = 24; **p < 0.01, ***p < 0.001, ****p < 0.0001

Constipation-Related Quality of Life Improved in All Treatment Groups, While Physical Activity was Unaltered

To examine the psychological and physical effects of reduced constipation-related symptoms as well as the impact of decreased defecation burden, we used the psychosocial PAC-QOL questionnaire in combination with the SIMPAQ. While the quality of life related to constipation was significantly increased as seen by significant reduction of PAC-QOL relative scores in all supplementation groups (Fig. 3a), the total self-reported time for physical activity during the week was not altered (Fig. 3b).

Fig. 3 — Evaluation of constipation-related impact on the quality of life (Patient Assessment of Constipation–Quality of Life, PAC-QOL) displayed a significant improvement in all supplementation groups, most prominent in the SCFA group (a), while physical activity was not influenced by supplementation regimens (b). Simple Physical Activity Questionnaire (SIMPAQ). Questionnaire results were displayed as individual values, while bar graphs show mean ± SEM. 3-month (V1) and 6-month (V2) clinical evaluations. Differences between time points within groups were statistically analyzed by two-way analysis of variance (ANOVA) in combination with Tukey’s test for multiple comparisons after verification of normal data distribution; 2-FL n = 23, SCFA n = 24, 2-FL + SCFA n = 24; *p < 0.05, **p < 0.01, ****p < 0.0001

Discussion

Here, we report that supplementation with SCFA and the prebiotic 2-FL lead to improvement of constipation-related symptoms in patients with PD. These findings demonstrate that combined supplementation with 2-FL and SCFA represents a promising therapeutic approach for addressing constipation. While individual interventions showed modest improvements, the combination produced superior and sustained benefits across multiple constipation-related parameters, supporting the therapeutic potential of targeting the constipation in patients with PD [32].

The supplementation with the combination of SCFA and 2-FL led to regulation of constipation symptoms across multiple assessment domains. Constipation is overall very burdensome for patients and entails many negative aspects, such as poorer medication absorption, while the use of laxatives is associated with dehydration, a disturbed water/salt balance, colonic ulcers, and ischemic colitis [33–36]. While the strongest effect on PD-specific outcomes (UPDRS) was observed in the SCFA group, as previously reported, the strongest effect on constipation was achieved in the combination group and in the 2-FL group after 6 months (Fig. 1) [19]. The observed improvement in constipation in the combination group may be explained by a potential synergistic effect of 2-FL and SCFAs, which together modulate gut microbiota composition, enhance intestinal barrier integrity, and attenuate local inflammation mechanisms known to influence gastrointestinal motility in PD. 2-FL may promote SCFA-producing bacteria such as Bifidobacterium, while exogenous SCFAs directly support mucosal function and enteric neuronal signaling, potentially restoring impaired gut–brain communication in Parkinson-related constipation [37–40]. Bowel dysfunction in patients with PD is increasingly recognized as a dual-component disorder involving both reduced defecation frequency (slow-transit constipation) and defecatory dysfunction (e.g., dyssynergia and straining), with the latter often representing the primary pathophysiological burden [41]. While the metabolic interventions explored here—SCFAs and the prebiotic 2-FL—primarily target intestinal factors such as mucosal integrity and enteric neuronal signaling, their clinical benefits appear to address both components. Specifically, these compounds may improve transit times by modulating local neurometabolic pathways, while the observed normalization of stool consistency (BSS) likely alleviates the mechanical difficulty and straining associated with defecatory dysfunction, leading to the more complete and satisfying evacuations reflected in our PAC-QOL and CCCS data.

The BSS demonstrated a resolution of constipation after 3 months in the combination group, indicating rapid normalization of stool form and consistency. This finding is particularly significant given that previous studies have shown that both 2-FL and SCFAs work synergistically to enhance intestinal barrier function and promote beneficial microbial fermentation [42]. Surprisingly, we observed a decrease in stool frequency in the combination group (Fig. 2b). At baseline, relatively high defecation frequencies in some patients may reflect incomplete evacuation or repeated attempts to defecate rather than normal bowel function, a phenomenon frequently observed in PD-related defecatory dysfunction. The observed reduction in frequency may therefore indicate a transition from multiple incomplete bowel movements toward fewer but more complete and effective evacuations. This apparent paradox may reflect the transition from multiple small, hard stools to fewer but more complete and satisfying bowel movements, as supported by the improved PAC-QOL scores [27]. The decreased frequency may be further elucidated by the components of the CCCS, which includes specific measures for defecatory dysfunction such as straining, incomplete evacuation, and time per defecation. The transition from frequent, unsuccessful attempts toward fewer but more efficient and complete bowel movements directly addresses the dyssynergic components often seen in patients with PD. In the combination group, this is evidenced by the simultaneous normalization of stool consistency (BSS) and reduced defecatory attempts. Conversely, the more pronounced PAC-QOL improvement in the SCFA group, despite stable bowel movement frequency, suggests that subjective quality of life in this cohort may also be influenced by the significant motor improvements previously observed with SCFA supplementation, alongside a reduction in the perceived burden of individual GI symptoms.

The PAC-QOL assessment revealed improved quality of life across all intervention groups, suggesting that even modest physiological improvements translate into meaningful patient-reported benefits. Although the absolute numerical changes in clinical scores were relatively modest, their clinical meaningfulness is underscored by the significant improvements observed in the PAC-QOL assessments. In patients with PD, even a subtle shift from hard, constipated stools (BSS 1–2) to a healthy consistency (BSS 3–4), combined with a reduction in unproductive defecation attempts, can represent a substantial relief in daily symptom burden and psychological distress. While minimal clinically important differences (MCID) for the CCCS in PD have not been universally established, the concurrent improvement in quality-of-life scores suggests that the observed physiological shifts provided tangible therapeutic benefits to the participants. Notably, the baseline severity of constipation in our cohort was relatively mild, with a mean CCCS score of approximately 8, which may limit the generalizability of our findings to patients with more severe or refractory constipation. This value is below the commonly used threshold of 15 for clinically significant constipation, indicating that our cohort predominantly represented patients with mild-to-moderate symptoms. However, baseline PAC-QOL scores demonstrated that even these comparatively mild symptoms were associated with a measurable impairment in quality of life, underscoring their clinical relevance in patients with PD. Although scores of 15 or higher are often considered indicative of clinically significant constipation, the baseline PAC-QOL results demonstrated that even these mild-to-moderate symptoms imposed a substantial subjective burden on participants’ quality of life. This suggests that the interventions addressed clinically relevant early-to-mid-stage symptomatic dysfunction rather than advanced constipation. While the CCCS is not a PD-specific instrument, it was chosen for its validated ability to assess components of defecatory dysfunction, including straining, incomplete evacuation, and time required for defecation, which are primary pathophysiological features of constipation in PD [20, 41]. The observed decrease in defecation frequency likely reflects a shift from frequent, unproductive attempts toward more complete bowel movements, a transition further supported by the significant improvement in patient-reported satisfaction and quality of life (PAC-QOL). Nevertheless, we acknowledge that our study did not utilize MDS-endorsed questionnaires or specifically monitor for overflow diarrhea and incontinence, which should be considered in future trials to more granularly characterize the clinical response. In addition, while the PAC-QOL provided valuable insights into constipation-specific distress, we did not include a general PD quality-of-life instrument (e.g., PDQ-39), which may have captured broader therapeutic effects. Future studies should therefore incorporate both disease-specific and symptom-specific quality-of-life measures to better delineate these interdependencies.

The efficacy observed in our study aligns with multiple lines of evidence supporting SCFA supplementation in constipation management. It has been demonstrated that acetate, PA, and BA levels were significantly decreased in patients with mixed refractory constipation and were negatively correlated with constipation severity, supporting our therapeutic rationale [43]. Similarly, Wang et al. showed that acetylated and butylated starches effectively relieved constipation by increasing acetate-producing bacteria, which correlated with small intestinal transit rate and water content of feces, while BA-producing bacteria were correlated with reduced time to first black stool defecation [38]. Our combination approach builds upon these findings by providing both direct SCFA supplementation and prebiotic substrate to sustain endogenous SCFA production. The duration of our intervention (6 months) exceeded that of most previous studies, which typically ranged from 4 to 8 weeks, potentially explaining the sustained benefits observed [11, 15, 44].

Epidemiological evidence indicates that physical activity generally exerts a beneficial effect on constipation in individuals with PD [45, 46]. Furthermore, as recently described, SCFAs improve motor abilities [19]. However, despite the positive effect on MDS-UPDRS III observed in the main study, an examination of the movement scores in this study shows that physical activity is unlikely to have contributed to the changes in constipation, as SIMPAQ mobility scores did not increase and remained stable across all three groups throughout the intervention period (Fig. 3b). This stability in physical activity further supports the assumption that major lifestyle-related confounders remained unchanged during the study period. Notably, subgroup analyses restricted to male participants largely confirmed the overall findings and indicated a particularly consistent response to combined 2-FL + SCFA supplementation across functional constipation outcomes (Supplementary Fig. 1).

While our study demonstrates significant clinical improvements, certain limitations must be acknowledged. First, the absence of a placebo-control group is a major limitation of this study. Although the randomized, three-arm design allowed for a direct comparison between different metabolic interventions, the lack of a placebo arm prevents us from fully isolating the therapeutic effect from potential placebo responses, which are common in clinical trials involving PD and gastrointestinal symptoms. Second, we did not perform physiological phenotyping (e.g., anorectal manometry or colonic transit studies) to categorize patients into specific constipation subtypes, such as slow transit or dyssynergic defecation, which is increasingly recognized as a primary pathophysiology in PD [41]. Consequently, we cannot exclude that our cohort included a heterogeneous mixture of constipation subtypes, including slow transit constipation, dyssynergic defecation, or overlapping forms, which may differentially respond to the investigated interventions. However, the CCCS applied in this study is a validated composite instrument that captures both stool frequency and key features of defecatory dysfunction, including straining, incomplete evacuation, and need for assistance, thereby partially reflecting the multifactorial nature of constipation in PD [20]. Third, although participants were advised to maintain consistent dietary habits, the lack of detailed longitudinal dietary records, including daily fiber intake, means we cannot entirely rule out the influence of dietary shifts on bowel habits. In particular, we did not systematically assess daily fiber intake at baseline, 3 months, and 6 months, which represents a potential confounder given the known impact of dietary composition on bowel function. Nevertheless, participants were explicitly instructed to maintain their habitual diet throughout the study period, and no structured dietary interventions were introduced. Future studies should integrate objective physiological measures and rigorous dietary monitoring to further delineate the mechanisms by which SCFAs and prebiotics influence specific constipation phenotypes in PD.

Study Limitations

This exploratory study has several limitations. The sample size was modest and no placebo group was included, limiting causal inference. Constipation outcomes were mainly questionnaire-based and were not complemented by objective physiological testing. Baseline symptoms were mostly mild to moderate, which may reduce generalizability to patients with severe constipation. Future studies should therefore include patients with more severe constipation to better assess the efficacy of these interventions across the full clinical spectrum of PD-related bowel dysfunction. In addition, unmeasured lifestyle factors such as diet or hydration may have influenced outcomes. Finally, the 6-month follow-up does not allow conclusions on long-term efficacy or safety.

Conclusions

This study demonstrates that combined supplementation with SCFA and 2-FL represents an effective and safe therapeutic strategy for managing constipation in patients with PD. The superior efficacy of combination therapy compared to individual interventions supports a synergistic mechanism involving both direct SCFA provision and enhanced endogenous production through prebiotic fermentation. These findings suggest that targeting constipation through microbiome-directed interventions may offer a valuable adjunctive treatment approach that improves both objective constipation parameters and patient-reported quality of life [47]. The sustained benefits observed over 6 months indicate that this approach may provide long-term therapeutic value.

Future research should explore optimal dosing regimens, investigate mechanistic pathways in greater detail, and evaluate the potential for disease-modifying effects beyond symptom management.

Supplementary Information

Below is the link to the electronic supplementary material.

40120_2026_972_MOESM1_ESM.tif^{(846.3KB, tif)}

Supplementary file1Fig. S1 Constipation-related symptoms and quality-of-life parameters in male patients with PD during supplementation with 2-FL, SCFAs, and combined treatment with 2-FL and SCFAs. 3-month (V1) and 6-month (V2) clinical evaluations. (A) Cleveland Clinic Constipation Score (CCCS) absolute points in male participants. Gray lines display individual patient scores at all study time points; black lines show mean ± SEM. (B) Bristol Stool Scale (BSS) scores in male participants demonstrating stool consistency and form during supplementation. Higher scores indicate stool forms associated with diarrhea, whereas lower scores indicate constipation-associated stool forms. (C) Defecation frequency in male participants, displayed as attempts per day. (D) Patient Assessment of Constipation–Quality of Life (PAC-QOL) relative points in male participants. (E) Physical activity assessed by the Simple Physical Activity Questionnaire (SIMPAQ), displayed as minutes of activity per week in male participants. Questionnaire results are displayed as individual values, while bar graphs show mean ± SEM. Differences between time points within groups were statistically analyzed by two-way ANOVA in combination with Tukey’s test for multiple comparisons after verification of normal data distribution. Only male participants were included in this analysis; 2-FL n = 15, SCFA n = 11, 2-FL + SCFA n = 11; *p < 0.05, **p < 0.01, ***p < 0.001 (TIF 846 KB)

Supplementary file2 (PDF 51 KB)^{(50.6KB, pdf)}

Acknowledgments

We would like to thank all study participants and the clinical staff involved for their valuable contributions and commitment to this study.

Medical Writing/Editorial Assistance

No medical writing or editorial assistance was received.

Authorship

All authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship and have approved the final version of the manuscript.

Author Contribution

Conceptualization: Tobias Hegelmaier and Aiden Haghikia; Methodology: Tobias Hegelmaier, Alexander Duscha and Christiane Desel; Formal analysis: Tobias Hegelmaier and Riccardo Troisi; Investigation: Tobias Hegelmaier, Lisa-Marie Würtele, Jana Peplinski and Diana Jauk; Writing – original draft: Tobias Hegelmaier, Alexander Duscha, Christiane Desel and Martin Klietz; Writing – review and editing: all authors; Supervision: Aiden Haghikia, Thomas Müller and Simon Faissner.

Funding

No funding or sponsorship was received for this study or publication of this article.

Data Availability

The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request but are not publicly available due to ethical and privacy considerations.

Declarations

Conflict of Interest

Tobias Hegelmaier, Alexander Duscha, Christiane Desel, Lisa-Marie Würtele, Jana Peplinski, Diana Jauk, Riccardo Troisi, Martin Klietz, Simon Faissner, and Aiden Haghikia have no conflicts of interest to disclose. Thomas Müller is an Editorial Board member of Neurology and Therapy. Thomas Müller was not involved in the selection of peer reviewers for the manuscript nor in any of the subsequent editorial decisions.

Ethical Approval

Footnotes

Tobias Hegelmaier, Alexander Duscha, Christiane Desel, and Aiden Haghikia contributed equally to this work.

References

1.Fasano A, Visanji NP, Liu LW, Lang AE, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol. 2015;14(6):625–39. [DOI] [PubMed] [Google Scholar]
2.Postuma RB, Gagnon JF, Pelletier A, Montplaisir J. Prodromal autonomic symptoms and signs in Parkinson’s disease and dementia with Lewy bodies. Mov Disord. 2013;28(5):597–604. [DOI] [PubMed] [Google Scholar]
3.Peters M, Hegelmaier T, Wegner F, et al. The role of the gut microbiome in the progression of Parkinson’s disease: a systematic review of patient cohorts. J Neurol. 2025;273(1):8. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Nair AT, Ramachandran V, Joghee NM, Antony S, Ramalingam G. Gut microbiota dysfunction as reliable non-invasive early diagnostic biomarkers in the pathophysiology of Parkinson’s disease: a critical review. J Neurogastroenterol Motil. 2018;24(1):30–42. [DOI] [PMC free article] [PubMed] [Google Scholar]
5.Bullich C, Keshavarzian A, Garssen J, Kraneveld A, Perez-Pardo P. Gut vibes in Parkinson’s disease: the microbiota-gut-brain axis. Mov Disord Clin Pract. 2019;6(8):639–51. [DOI] [PMC free article] [PubMed] [Google Scholar]
6.Park J, Kim CH. Regulation of common neurological disorders by gut microbial metabolites. Exp Mol Med. 2021;53(12):1821–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
7.Barbara G, Barbaro MR, Fuschi D, et al. Inflammatory and microbiota-related regulation of the intestinal epithelial barrier. Front Nutr. 2021;8:718356. [DOI] [PMC free article] [PubMed] [Google Scholar]
8.Martin-Gallausiaux C, Marinelli L, Blottiere HM, Larraufie P, Lapaque N. SCFA: mechanisms and functional importance in the gut. Proc Nutr Soc. 2021;80(1):37–49. [DOI] [PubMed] [Google Scholar]
9.Bairamian D, Sha S, Rolhion N, et al. Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease. Mol Neurodegener. 2022;17(1):19. [DOI] [PMC free article] [PubMed] [Google Scholar]
10.Sharma A, Voigt RM, Goetz CG, Keshavarzian A. Parkinson disease and the gut: a primer for gastroenterologists. Am J Gastroenterol. 2025;120(11):2510–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
11.Barichella M, Pacchetti C, Bolliri C, et al. Probiotics and prebiotic fiber for constipation associated with Parkinson disease: an RCT. Neurology. 2016;87(12):1274–80. [DOI] [PubMed] [Google Scholar]
12.Cassani E, Privitera G, Pezzoli G, et al. Use of probiotics for the treatment of constipation in Parkinson’s disease patients. Minerva Gastroenterol Dietol. 2011;57(2):117–21. [PubMed] [Google Scholar]
13.Mohr AE, Basile AJ, Crawford MS, Sweazea KL, Carpenter KC. Probiotic supplementation has a limited effect on circulating immune and inflammatory markers in healthy adults: a systematic review of randomized controlled trials. J Acad Nutr Diet. 2020;120(4):548–64. [DOI] [PubMed] [Google Scholar]
14.Tamtaji OR, Taghizadeh M, Daneshvar Kakhaki R, et al. Clinical and metabolic response to probiotic administration in people with Parkinson’s disease: a randomized, double-blind, placebo-controlled trial. Clin Nutr. 2019;38(3):1031–5 (Article retracted). [DOI] [PubMed] [Google Scholar]
15.Tan AH, Lim SY, Chong KK, et al. Probiotics for constipation in Parkinson disease: a randomized placebo-controlled study. Neurology. 2021;96(5):e772–82. 10.1212/WNL.0000000000010998. [DOI] [PubMed] [Google Scholar]
16.Bedarf JR, Romano S, Heinzmann SS, et al. A prebiotic dietary pilot intervention restores faecal metabolites and may be neuroprotective in Parkinson’s disease. npj Parkinsons Dis. 2025;11(1):66. [DOI] [PMC free article] [PubMed] [Google Scholar]
17.Hall DA, Voigt RM, Cantu-Jungles TM, et al. An open label, non-randomized study assessing a prebiotic fiber intervention in a small cohort of Parkinson’s disease participants. Nat Commun. 2023;14(1):926. [DOI] [PMC free article] [PubMed] [Google Scholar]
18.Ryan JJ, Monteagudo-Mera A, Contractor N, Gibson GR. Impact of 2′-fucosyllactose on gut microbiota composition in adults with chronic gastrointestinal conditions: batch culture fermentation model and pilot clinical trial findings. Nutrients. 2021. 10.3390/nu13030938. [DOI] [PMC free article] [PubMed] [Google Scholar]
19.Hegelmaier T, Duscha A, Desel C, et al. Supplementation with short-chain fatty acids and a prebiotic improves clinical outcome in Parkinson’s disease: a randomized double-blind prospective study. Sci Rep. 2025;16(1):315. [DOI] [PMC free article] [PubMed] [Google Scholar]
20.Agachan F, Chen T, Pfeifer J, Reissman P, Wexner SD. A constipation scoring system to simplify evaluation and management of constipated patients. Dis Colon Rectum. 1996;39(6):681–5. [DOI] [PubMed] [Google Scholar]
21.Froehner Junior I, Jorge JMN, Marques CFS, Santos V, Jukemura J. Constipation scoring system validated for the Portuguese language (Indice De Gravidade Da Constipacao Intestinal): is it reliable in assessing the severity of intestinal chronic constipation in our population? Arq Bras Cir Dig. 2024;36:e1785. 10.1590/0102-672020230067e1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
22.Knowles CH, Eccersley AJ, Scott SM, Walker SM, Reeves B, Lunniss PJ. Linear discriminant analysis of symptoms in patients with chronic constipation: validation of a new scoring system (KESS). Dis Colon Rectum. 2000;43(10):1419–26. [DOI] [PubMed] [Google Scholar]
23.Majidirad F, Hadian MR, Asl Soleimani H, et al. Cross-cultural adaptation, validity, and reliability of the Wexner questionnaire in patients with functional constipation in an Iranian population. Gastroenterol Hepatol Bed Bench. 2021;14(3):243–9. [PMC free article] [PubMed] [Google Scholar]
24.Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997;32(9):920–4. [DOI] [PubMed] [Google Scholar]
25.Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130(5):1480–91. [DOI] [PubMed] [Google Scholar]
26.Silva L, Dias FC, Melli L, Tahan S, Morais MB. Clinical spectrum of functional constipation and bowel-habit patterns of schoolchildren recruited from two elementary schools and a specialized outpatient clinic. Arq Gastroenterol. 2022;59(2):263–7. [DOI] [PubMed] [Google Scholar]
27.Marquis P, De La Loge C, Dubois D, McDermott A, Chassany O. Development and validation of the Patient Assessment of Constipation Quality of Life questionnaire. Scand J Gastroenterol. 2005;40(5):540–51. [DOI] [PubMed] [Google Scholar]
28.Cobo Dols M, Beato Zambrano C, Cabezon-Gutierrez L, et al. One-year efficacy and safety of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: KYONAL study. BMJ Support Palliat Care. 2023;13(e2):e318–26. 10.1136/bmjspcare-2020-002816. [DOI] [PMC free article] [PubMed] [Google Scholar]
29.Li D, Li H, Liu H, et al. Impact of electroacupuncture stimulation on postoperative constipation for patients undergoing brain tumor surgery. J Neurosci Nurs. 2020;52(5):257–62. [DOI] [PubMed] [Google Scholar]
30.Rosenbaum S, Morell R, Abdel-Baki A, et al. Assessing physical activity in people with mental illness: 23-country reliability and validity of the simple physical activity questionnaire (SIMPAQ). BMC Psychiatry. 2020;20(1):108. [DOI] [PMC free article] [PubMed] [Google Scholar]
31.Tavares VDO, de Sousa GM, Schuch FB, et al. Self-reported mood and lifestyle-related physical activity of young adults with major depressive disorder. Percept Mot Skills. 2024;131(2):489–513. [DOI] [PubMed] [Google Scholar]
32.Loh JS, Mak WQ, Tan LKS, et al. Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases. Signal Transduct Target Ther. 2024;9(1):37. [DOI] [PMC free article] [PubMed] [Google Scholar]
33.Astarloa R, Mena MA, Sanchez V, de la Vega L, de Yebenes JG. Clinical and pharmacokinetic effects of a diet rich in insoluble fiber on Parkinson disease. Clin Neuropharmacol. 1992;15(5):375–80. [DOI] [PubMed] [Google Scholar]
34.Choi SI, Choi J. Ischaemic colitis caused by polyethylene glycol with ascorbic acid bowel preparation agent. BMJ Case Rep. 2021;14(11)e245891. [DOI] [PMC free article] [PubMed]
35.Kolosionek TJ, Jiang RY, Meleis MM, Ebeling-Koning NE, Surmaitis RM. Polyethylene glycol misuse causing acute renal failure and metabolic acidosis requiring dialysis: a case report. Cureus. 2024;16(7):e65838. [DOI] [PMC free article] [PubMed] [Google Scholar]
36.Reumkens A, van der Zander Q, Winkens B, et al. Electrolyte disturbances after bowel preparation for colonoscopy: systematic review and meta-analysis. Dig Endosc. 2022;34(5):913–26. [DOI] [PMC free article] [PubMed] [Google Scholar]
37.Unger MM, Spiegel J, Dillmann KU, et al. Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Parkinsonism Relat Disord. 2016;32:66–72. [DOI] [PubMed] [Google Scholar]
38.Wang L, Cen S, Wang G, et al. Acetic acid and butyric acid released in large intestine play different roles in the alleviation of constipation. J Funct Foods. 2020;69:103953. [Google Scholar]
39.Ren X, Xiao M, Zhang L, et al. Impact of 2′-fucosyllactose on adult gut microbiota composition and metabolome based on colonic fermentation and prebiotic quantitative evaluation. J Food Sci. 2025;90(3):e70084. 10.1111/1750-3841.70084. [DOI] [PubMed] [Google Scholar]
40.Lee S, Goodson ML, Vang W, et al. Human milk oligosaccharide 2′-fucosyllactose supplementation improves gut barrier function and signaling in the vagal afferent pathway in mice. Food Funct. 2021;12(18):8507–21. [DOI] [PMC free article] [PubMed] [Google Scholar]
41.Quigley EMM. Constipation in Parkinson’s disease. Semin Neurol. 2023;43(4):562–71. [DOI] [PubMed] [Google Scholar]
42.Xiong R-G, Zhou D-D, Wu S-X, et al. Health benefits and side effects of short-chain fatty acids. Foods. 2022;11(18):2863. [DOI] [PMC free article] [PubMed] [Google Scholar]
43.Shi Y, Chen Q, Huang Y, et al. Function and clinical implications of short-chain fatty acids in patients with mixed refractory constipation. Colorectal Dis. 2016;18(8):803–10. [DOI] [PubMed] [Google Scholar]
44.Ibrahim A, Ali RAR, Manaf MRA, et al. Multi-strain probiotics (Hexbio) containing MCP BCMC strains improved constipation and gut motility in Parkinson’s disease: a randomised controlled trial. PLoS ONE. 2020;15(12):e0244680. 10.1371/journal.pone.0244680. [DOI] [PMC free article] [PubMed] [Google Scholar]
45.Bhalsing KS, Abbas MM, Tan LC. Role of physical activity in Parkinson’s disease. Ann Indian Acad Neurol. 2018;21(4):242–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
46.Hughes KC, Gao X, Molsberry S, Valeri L, Schwarzschild MA, Ascherio A. Physical activity and prodromal features of Parkinson disease. Neurology. 2019;93(23):e2157–69. 10.1212/WNL.0000000000008567. [DOI] [PMC free article] [PubMed] [Google Scholar]
47.Zangaglia R, Martignoni E, Glorioso M, et al. Macrogol for the treatment of constipation in Parkinson’s disease. A randomized placebo-controlled study. Mov Disord. 2007;22(9):1239–44. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

40120_2026_972_MOESM1_ESM.tif^{(846.3KB, tif)}

Supplementary file2 (PDF 51 KB)^{(50.6KB, pdf)}

Data Availability Statement

[CR1] 1.Fasano A, Visanji NP, Liu LW, Lang AE, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol. 2015;14(6):625–39. [DOI] [PubMed] [Google Scholar]

[CR2] 2.Postuma RB, Gagnon JF, Pelletier A, Montplaisir J. Prodromal autonomic symptoms and signs in Parkinson’s disease and dementia with Lewy bodies. Mov Disord. 2013;28(5):597–604. [DOI] [PubMed] [Google Scholar]

[CR3] 3.Peters M, Hegelmaier T, Wegner F, et al. The role of the gut microbiome in the progression of Parkinson’s disease: a systematic review of patient cohorts. J Neurol. 2025;273(1):8. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR4] 4.Nair AT, Ramachandran V, Joghee NM, Antony S, Ramalingam G. Gut microbiota dysfunction as reliable non-invasive early diagnostic biomarkers in the pathophysiology of Parkinson’s disease: a critical review. J Neurogastroenterol Motil. 2018;24(1):30–42. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR5] 5.Bullich C, Keshavarzian A, Garssen J, Kraneveld A, Perez-Pardo P. Gut vibes in Parkinson’s disease: the microbiota-gut-brain axis. Mov Disord Clin Pract. 2019;6(8):639–51. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR6] 6.Park J, Kim CH. Regulation of common neurological disorders by gut microbial metabolites. Exp Mol Med. 2021;53(12):1821–33. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR7] 7.Barbara G, Barbaro MR, Fuschi D, et al. Inflammatory and microbiota-related regulation of the intestinal epithelial barrier. Front Nutr. 2021;8:718356. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR8] 8.Martin-Gallausiaux C, Marinelli L, Blottiere HM, Larraufie P, Lapaque N. SCFA: mechanisms and functional importance in the gut. Proc Nutr Soc. 2021;80(1):37–49. [DOI] [PubMed] [Google Scholar]

[CR9] 9.Bairamian D, Sha S, Rolhion N, et al. Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease. Mol Neurodegener. 2022;17(1):19. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR10] 10.Sharma A, Voigt RM, Goetz CG, Keshavarzian A. Parkinson disease and the gut: a primer for gastroenterologists. Am J Gastroenterol. 2025;120(11):2510–9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR11] 11.Barichella M, Pacchetti C, Bolliri C, et al. Probiotics and prebiotic fiber for constipation associated with Parkinson disease: an RCT. Neurology. 2016;87(12):1274–80. [DOI] [PubMed] [Google Scholar]

[CR12] 12.Cassani E, Privitera G, Pezzoli G, et al. Use of probiotics for the treatment of constipation in Parkinson’s disease patients. Minerva Gastroenterol Dietol. 2011;57(2):117–21. [PubMed] [Google Scholar]

[CR13] 13.Mohr AE, Basile AJ, Crawford MS, Sweazea KL, Carpenter KC. Probiotic supplementation has a limited effect on circulating immune and inflammatory markers in healthy adults: a systematic review of randomized controlled trials. J Acad Nutr Diet. 2020;120(4):548–64. [DOI] [PubMed] [Google Scholar]

[CR14] 14.Tamtaji OR, Taghizadeh M, Daneshvar Kakhaki R, et al. Clinical and metabolic response to probiotic administration in people with Parkinson’s disease: a randomized, double-blind, placebo-controlled trial. Clin Nutr. 2019;38(3):1031–5 (Article retracted). [DOI] [PubMed] [Google Scholar]

[CR15] 15.Tan AH, Lim SY, Chong KK, et al. Probiotics for constipation in Parkinson disease: a randomized placebo-controlled study. Neurology. 2021;96(5):e772–82. 10.1212/WNL.0000000000010998. [DOI] [PubMed] [Google Scholar]

[CR16] 16.Bedarf JR, Romano S, Heinzmann SS, et al. A prebiotic dietary pilot intervention restores faecal metabolites and may be neuroprotective in Parkinson’s disease. npj Parkinsons Dis. 2025;11(1):66. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR17] 17.Hall DA, Voigt RM, Cantu-Jungles TM, et al. An open label, non-randomized study assessing a prebiotic fiber intervention in a small cohort of Parkinson’s disease participants. Nat Commun. 2023;14(1):926. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR18] 18.Ryan JJ, Monteagudo-Mera A, Contractor N, Gibson GR. Impact of 2′-fucosyllactose on gut microbiota composition in adults with chronic gastrointestinal conditions: batch culture fermentation model and pilot clinical trial findings. Nutrients. 2021. 10.3390/nu13030938. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR19] 19.Hegelmaier T, Duscha A, Desel C, et al. Supplementation with short-chain fatty acids and a prebiotic improves clinical outcome in Parkinson’s disease: a randomized double-blind prospective study. Sci Rep. 2025;16(1):315. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR20] 20.Agachan F, Chen T, Pfeifer J, Reissman P, Wexner SD. A constipation scoring system to simplify evaluation and management of constipated patients. Dis Colon Rectum. 1996;39(6):681–5. [DOI] [PubMed] [Google Scholar]

[CR21] 21.Froehner Junior I, Jorge JMN, Marques CFS, Santos V, Jukemura J. Constipation scoring system validated for the Portuguese language (Indice De Gravidade Da Constipacao Intestinal): is it reliable in assessing the severity of intestinal chronic constipation in our population? Arq Bras Cir Dig. 2024;36:e1785. 10.1590/0102-672020230067e1785. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR22] 22.Knowles CH, Eccersley AJ, Scott SM, Walker SM, Reeves B, Lunniss PJ. Linear discriminant analysis of symptoms in patients with chronic constipation: validation of a new scoring system (KESS). Dis Colon Rectum. 2000;43(10):1419–26. [DOI] [PubMed] [Google Scholar]

[CR23] 23.Majidirad F, Hadian MR, Asl Soleimani H, et al. Cross-cultural adaptation, validity, and reliability of the Wexner questionnaire in patients with functional constipation in an Iranian population. Gastroenterol Hepatol Bed Bench. 2021;14(3):243–9. [PMC free article] [PubMed] [Google Scholar]

[CR24] 24.Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997;32(9):920–4. [DOI] [PubMed] [Google Scholar]

[CR25] 25.Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130(5):1480–91. [DOI] [PubMed] [Google Scholar]

[CR26] 26.Silva L, Dias FC, Melli L, Tahan S, Morais MB. Clinical spectrum of functional constipation and bowel-habit patterns of schoolchildren recruited from two elementary schools and a specialized outpatient clinic. Arq Gastroenterol. 2022;59(2):263–7. [DOI] [PubMed] [Google Scholar]

[CR27] 27.Marquis P, De La Loge C, Dubois D, McDermott A, Chassany O. Development and validation of the Patient Assessment of Constipation Quality of Life questionnaire. Scand J Gastroenterol. 2005;40(5):540–51. [DOI] [PubMed] [Google Scholar]

[CR28] 28.Cobo Dols M, Beato Zambrano C, Cabezon-Gutierrez L, et al. One-year efficacy and safety of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: KYONAL study. BMJ Support Palliat Care. 2023;13(e2):e318–26. 10.1136/bmjspcare-2020-002816. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR29] 29.Li D, Li H, Liu H, et al. Impact of electroacupuncture stimulation on postoperative constipation for patients undergoing brain tumor surgery. J Neurosci Nurs. 2020;52(5):257–62. [DOI] [PubMed] [Google Scholar]

[CR30] 30.Rosenbaum S, Morell R, Abdel-Baki A, et al. Assessing physical activity in people with mental illness: 23-country reliability and validity of the simple physical activity questionnaire (SIMPAQ). BMC Psychiatry. 2020;20(1):108. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR31] 31.Tavares VDO, de Sousa GM, Schuch FB, et al. Self-reported mood and lifestyle-related physical activity of young adults with major depressive disorder. Percept Mot Skills. 2024;131(2):489–513. [DOI] [PubMed] [Google Scholar]

[CR32] 32.Loh JS, Mak WQ, Tan LKS, et al. Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases. Signal Transduct Target Ther. 2024;9(1):37. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR33] 33.Astarloa R, Mena MA, Sanchez V, de la Vega L, de Yebenes JG. Clinical and pharmacokinetic effects of a diet rich in insoluble fiber on Parkinson disease. Clin Neuropharmacol. 1992;15(5):375–80. [DOI] [PubMed] [Google Scholar]

[CR34] 34.Choi SI, Choi J. Ischaemic colitis caused by polyethylene glycol with ascorbic acid bowel preparation agent. BMJ Case Rep. 2021;14(11)e245891. [DOI] [PMC free article] [PubMed]

[CR35] 35.Kolosionek TJ, Jiang RY, Meleis MM, Ebeling-Koning NE, Surmaitis RM. Polyethylene glycol misuse causing acute renal failure and metabolic acidosis requiring dialysis: a case report. Cureus. 2024;16(7):e65838. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR36] 36.Reumkens A, van der Zander Q, Winkens B, et al. Electrolyte disturbances after bowel preparation for colonoscopy: systematic review and meta-analysis. Dig Endosc. 2022;34(5):913–26. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR37] 37.Unger MM, Spiegel J, Dillmann KU, et al. Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Parkinsonism Relat Disord. 2016;32:66–72. [DOI] [PubMed] [Google Scholar]

[CR38] 38.Wang L, Cen S, Wang G, et al. Acetic acid and butyric acid released in large intestine play different roles in the alleviation of constipation. J Funct Foods. 2020;69:103953. [Google Scholar]

[CR39] 39.Ren X, Xiao M, Zhang L, et al. Impact of 2′-fucosyllactose on adult gut microbiota composition and metabolome based on colonic fermentation and prebiotic quantitative evaluation. J Food Sci. 2025;90(3):e70084. 10.1111/1750-3841.70084. [DOI] [PubMed] [Google Scholar]

[CR40] 40.Lee S, Goodson ML, Vang W, et al. Human milk oligosaccharide 2′-fucosyllactose supplementation improves gut barrier function and signaling in the vagal afferent pathway in mice. Food Funct. 2021;12(18):8507–21. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR41] 41.Quigley EMM. Constipation in Parkinson’s disease. Semin Neurol. 2023;43(4):562–71. [DOI] [PubMed] [Google Scholar]

[CR42] 42.Xiong R-G, Zhou D-D, Wu S-X, et al. Health benefits and side effects of short-chain fatty acids. Foods. 2022;11(18):2863. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR43] 43.Shi Y, Chen Q, Huang Y, et al. Function and clinical implications of short-chain fatty acids in patients with mixed refractory constipation. Colorectal Dis. 2016;18(8):803–10. [DOI] [PubMed] [Google Scholar]

[CR44] 44.Ibrahim A, Ali RAR, Manaf MRA, et al. Multi-strain probiotics (Hexbio) containing MCP BCMC strains improved constipation and gut motility in Parkinson’s disease: a randomised controlled trial. PLoS ONE. 2020;15(12):e0244680. 10.1371/journal.pone.0244680. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR45] 45.Bhalsing KS, Abbas MM, Tan LC. Role of physical activity in Parkinson’s disease. Ann Indian Acad Neurol. 2018;21(4):242–9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR46] 46.Hughes KC, Gao X, Molsberry S, Valeri L, Schwarzschild MA, Ascherio A. Physical activity and prodromal features of Parkinson disease. Neurology. 2019;93(23):e2157–69. 10.1212/WNL.0000000000008567. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR47] 47.Zangaglia R, Martignoni E, Glorioso M, et al. Macrogol for the treatment of constipation in Parkinson’s disease. A randomized placebo-controlled study. Mov Disord. 2007;22(9):1239–44. [DOI] [PubMed] [Google Scholar]

PERMALINK

Prebiotics and SCFA Alleviate Parkinson’s-Related Constipation: Results from a Randomized Controlled Trial

Tobias Hegelmaier

Alexander Duscha

Christiane Desel

Lisa-Marie Würtele

Jana Peplinski

Diana Jauk

Riccardo Troisi

Martin Klietz

Simon Faissner

Thomas Müller

Aiden Haghikia

Abstract

Introduction

Methods

Results

Conclusion

Trial Registry

Supplementary Information

Plain Language Summary

Supplementary Information

Key Summary Points

Introduction

Methods

Study Design and Participants

Table 1.

Ethical Approval

Randomization and Masking

Cleveland Clinic Constipation Score (CCCS)

Bristol Stool Scale (BSS) and Defecation Frequencies

Patient Assessment of Constipation–Quality of Life (PAC-QOL)

Simple Physical Activity Questionnaire (SIMPAQ)

Results

Constipation-Related Symptoms Decreased During 6 Months of Prebiotic and SCFA Supplementation

Fig. 1.

Stool Form and Defecation Frequency Improved During Prebiotic and SCFA Supplementation

Fig. 2.

Constipation-Related Quality of Life Improved in All Treatment Groups, While Physical Activity was Unaltered

Fig. 3.

Discussion

Study Limitations

Conclusions

Supplementary Information

Acknowledgments

Medical Writing/Editorial Assistance

Authorship

Author Contribution

Funding

Data Availability

Declarations

Conflict of Interest

Ethical Approval

Footnotes

References

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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