Correction: Zhu et al. Gait Analysis with Wearables Is a Potential Progression Marker in Parkinson's Disease. Brain Sci. 2022, 12, 1213.

In the original publication [...].

Minor hallucinations in Parkinson's disease with probable rapid eye movement sleep behavior disorder.

Background: Rapid eye movement sleep behavior disorder (RBD) and minor hallucinations (MHs) are prevalent nonmotor symptoms in Parkinson's disease (PD). The purpose of this study was to explore the association of MHs in PD patients with probable RBD (pRBD). Methods: This cross-sectional study included 291 patients diagnosed with PD. Patients who scored 6 or higher on the Rapid Eye Movement Behavior Disorder (RBD) Screening Questionnaire were defined as pRBD. A comprehensive evaluation was performed for all patients, including the collection of demographic information, clinical assessment, and MH features. Results: Among the 291 PD patients, 69 (23.7%) had pRBD. MHs were observed in 35 (50.7%) patients with pRBD, significantly higher than 29.7% in patients without RBD (p = 0.015). The main type of MHs in pRBD was presence hallucinations with variable content. Patients with pRBD and MHs tended to be older, had a longer disease duration, and were more likely to take levodopa or dopamine-receptor agonists. Besides, the pRBD with MHs group had higher scores on the Nonmotor Symptoms Questionnaire (NMS-Quest) and Hamilton Anxiety Scale (HAMA). Binary logistic regression analysis revealed that longer disease duration and higher NMS-Quest scores were associated with MHs in PD patients with pRBD. Conclusion: A high prevalence of MHs was observed in PD patients with pRBD. The main type of MHs in pRBD was presence hallucinations. MHs in PD with RBD are mainly associated with disease duration and severity of nonmotor symptoms. These findings provide new insights into the interaction between MHs and RBD.

Sleep structure and related clinical characteristics in drug-naïve Parkinson's disease with subjectively different sleep quality.

Background: Sleep disturbance is a common non-motor symptom of Parkinson's disease (PD). Most polysomnography (PSG) studies are conducted when patients are in their "on medication" state. Our study aimed to investigate changes in the sleep structure in drug-naive PD patients with poor subjective sleep quality based on polysomnography (PSG) and to explore potential correlations between sleep structure and clinical features of the disease. Methods: A total of 44 drug-naive PD patients were included. All patients completed a standardized questionnaire to obtain demographic and clinical characteristics and underwent whole-night PSG recording. Patients with PSQI scores >5.5 were considered poor sleepers, and patients with PSQI scores <5.5 were considered to be good sleepers. Results: There were 24 (54.5%) PD patients in the good sleeper group and 20 (24.5%) PD patients in the poor sleeper group. We observed that poor sleepers had severe non-motor symptoms (NMS) and worse life quality. The PSG displayed that they had a longer wake-up time after sleep onset (WASO) and lower sleep efficiency (SE). Correlation analysis revealed that the micro-arousal index was positively associated with UPDRS-III, and the N1 sleep percentage was negatively associated with the NMS score in good sleepers. For poor sleepers, rapid eye movement (REM) sleep percentage was negatively related to the Hoehn-Yahr (H-Y) stage, WASO increased with UPDRS-III, periodic limb movement index (PLMI) increased with the NMS score, and N2 sleep percentage was negatively related to the score of life quality. Conclusion: Night awakening is the main manifestation of decreased sleep quality in drug-naive PD patients. Poor sleepers have severe non-motor symptoms and poor life quality. Additionally, the increase in nocturnal arousal events may predict the progression of motor dysfunction.

Clinical features of minor hallucinations in different phenotypes of Parkinson's disease: A cross-sectional study.

Background: Minor hallucinations (MHs) are the most common psychiatric symptom associated with Parkinson's disease (PDPsy), but little is known about their characteristics in different motor phenotypes, especially postural instability gait difficulty (PIGD). The aim of this study was to explore the clinical features of MHs in different subtypes of PD. Methods: In this cross-sectional study, 213 patients with Parkinson's disease (PD) were recruited, and the data obtained included comprehensive demographics, motor subtypes, clinical scale scores, and MH contents. Motor subtypes were classified as tremor-dominant (TD), PIGD or indeterminate according to Stebbins' method. Results: A total of 213 PD patients were included: 90 (42.3%) TD patients, 98 (46.0%) PIGD patients and 25 (11.7%) indeterminate. In total, 70 (32.9%) patients experienced MHs. Compared to patients with the TD phenotype, we found that patients with the PIGD phenotype had more severe motor and nonmotor symptoms. They also had a higher incidence of visual illusions (VIs) and a shorter MH latency. Conclusion: Our study demonstrated that compared to patients with the TD phenotype, patients with the PIGD phenotype had a higher incidence of MHs, especially VIs, which may lead to a higher incidence of visual hallucinations (VHs). They also had a shorter latency of MHs than patients with the TD phenotype, suggesting an earlier onset of MHs and a worse prognosis.

[Cloning and catalytic analysis of Isatis indigotica chalcone isomerase in vitro].

Chalcone isomerase is a key rate-limiting enzyme in the biosynthesis of flavonoids in higher plants, which determines the production of flavonoids in plants. In this study, RNA was extracted from different parts of Isatis indigotica and reverse-transcribed into cDNA. Specific primers with enzyme restriction sites were designed, and a chalcone isomerase gene was cloned from I. indigotica, named IiCHI. IiCHI was 756 bp in length, containing a complete open reading frame and encoding 251 amino acids. Homology analysis showed that IiCHI was closely related to CHI protein of Arabidopsis thaliana and had typical active sites of chalcone isomerase. Phylogenetic tree analysis showed that IiCHI was classified into type Ⅰ CHI clade. Recombinant prokaryotic expression vector pET28a-IiCHI was constructed and purified to obtain IiCHI recombinant protein. In vitro enzymatic analysis showed that the IiCHI protein could convert naringenin chalcone into naringenin, but could not catalyze the production of liquiritigenin by isoliquiritigenin. The results of real-time quantitative polymerase chain reaction(qPCR) showed that the expression level of IiCHI in the aboveground parts was higher than that in the underground parts and the expression level was the highest in the flowers of the aboveground parts, followed by leaves and stems, and no expression was observed in the roots and rhizomes of the underground parts. This study has confirmed the function of chalcone isomerase in I. indigotica and provided references for the biosynthesis of flavonoid components.

The relationship between obstructive sleep apnea and visual hallucinations in PD patients: a polysomnography study.

Purpose: Parkinson's disease (PD) patients frequently experience visual hallucinations (VHs) and obstructive sleep apnea (OSA). The aim of this study was to describe the prevalence and clinical correlates of VHs and OSA in the Chinese population with PD. Materials and methods: A sample of 489 PD patients was recruited for the present study. Patients were categorized as having formed VHs (FVHs) or minor VHs (MVHs) or as non-hallucinators (NVHs) according to the Unified Parkinson's Disease Rating Scale (UPDRS) and an initial questionnaire. Polysomnography (PSG) was used for objective assessment of sleep. Results: VHs were observed in 143 (29.2%) patients. Among them, 75 of the hallucinators experienced MVHs, and 68 experienced FVHs. The disease duration, UPDRS Part III score, Hoehn and Yahr (H-Y) stage, Pittsburgh Sleep Quality Index (PSQI) score and rapid eye movement (REM) sleep behavior disorder (RBD) score of hallucinators were significantly greater than those of non-hallucinators (P < 0.05). We also observed OSA in 38.7, 54.7, and 63.3% of the NVH, MVH, and FVH groups, respectively. PSG showed that the VH groups had a lower total sleep time, lower sleep efficiency, higher arousal index, lower sleep latency, lower N1%, higher apnea-hypopnea index (AHI), higher average duration of apnea, higher respiratory-related arousal (RRA), and lower values of the lowest O2 and mean O2. The forward binary logistic regression model showed that AHI, N1%, RRA and lowest O2 were independently associated with VHs in PD patients. Conclusions: Our results confirm the high prevalence of VHs and OSA as well as their relationship in patients with PD.

Alterations of Regional Homogeneity in Parkinson's Disease with Rapid Eye Movement Sleep Behavior Disorder.

Objective: Patients with rapid eye movement (REM) sleep behavior disorder (RBD) in Parkinson's disease (PD-RBD) tend to have poor cognitive performance and faster cognitive deterioration, and the potential mechanism is still ambiguous. Therefore, this study aimed to detect the alterations in local brain function in PD-RBD. Methods: Fifty patients, including 23 patients with PD-RBD and 27 patients with PD without RBD (PD-nRBD), and 26 healthy controls were enrolled. All subjects were subjected to one-night polysomnography and underwent resting-state functional magnetic resonance imaging (rs-fMRI). The fMRI images of the three groups were analyzed by regional homogeneity (ReHo) to observe the local neural activity. Correlations between altered ReHo values and chin electromyographic (EMG) density scores and cognitive scores in the PD subgroups were assessed. Results: Compared with the patients with PD-nRBD, the patients with PD-RBD had higher ReHo values in the frontal cortex (the right superior frontal gyrus, the right middle frontal gyrus and the left medial superior frontal gyrus), the right caudate nucleus and the right anterior cingulate gyrus, and compared with the HCs, the patients with PD-RBD had lower ReHo values in the bilateral cuneus, the bilateral precuneus, the left inferior temporal gyrus and the left inferior occipital gyrus. For the patients with PD-RBD, the phasic chin EMG density scores were positively correlated with the ReHo values in the left medial superior frontal gyrus, and the tonic chin EMG density scores were positively correlated with the ReHo values in the right anterior cingulate gyrus. Conclusion: This study indicates that increased ReHo in the frontal cortex, the caudate nucleus and the anterior cingulate gyrus may be linked with the abnormal motor behaviors during REM sleep and that decreased ReHo in the posterior regions may be related to the visuospatial-executive function in patients with PD-RBD.

Characteristics of sleep structure in Parkinson's disease patients with hallucinations based on polysomnography.

Hallucination is a common non-motor symptom in patients with Parkinson's disease (PD). Additionally, sleep disorders are associated with an increased risk of hallucinations in PD patients. This study aimed to examine the association between hallucination and objective sleep parameters in PD patients. We retrospectively recruited 278 PD patients who underwent polysomnography and clinical assessments and classified them into non-hallucination and hallucination groups. Hallucinations were observed in 77 older PD patients who had more severe motor symptoms and higher scores on the Non-Motor Symptoms Questionnaire (NMSQ), Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) but lower scores on the Montreal Cognitive Assessment (MOCA) and PD Sleep Scale (PDSS) than PD patients without hallucinations. Analysis of the polysomnographic variables in patients with hallucinations showed that they exhibited a decrease in total sleep time, sleep efficiency (SE), rapid eye movement (REM) sleep time and slow wave sleep (SWS, N3) time and percentage but a significant increase in wake time after sleep onset (WASO), periodic limb movement index (PLMI) scores, and stage 2 NREM (N2)percentage. Logistic regression analysis revealed that higher NMSQ scores, lower MOCA scores, lower SE, and a lower percentage of N3 sleep were associated with hallucinations in PD patients. Our results suggested that PD patients with hallucinations had worse sleep quality and differences in sleep architecture (measured by polysomnography).

Aberrant gray matter volume and functional connectivity in Parkinson's disease with minor hallucination.

Background: Minor hallucination (MH) is the most common psychotic symptom in Parkinson's disease (PD); it can develop into well-structured visual hallucination (VH), suggesting that MH may be a staccato form of well-structured VH. However, it remains unclear whether the pathogenesis is the same. Therefore, the aim of this study was to investigate the altered gray matter volume (GMV) and functional connectivity (FC) of MH in PD to further understand the complex mechanisms. Materials and methods: We included 67 PD patients who attended the outpatient clinic of Nanjing Medical University Affiliated Brain Hospital and recruited 31 healthy controls (HC). Demographic data and clinical characteristics of all subjects were recorded, and cranial structural magnetic resonance imaging (MRI) and resting-state functional MRI data were acquired. Patients were classified into the PD with MH (PD-MH) group and PD without hallucinations or delusions (PD-NH) group. Voxel-based morphometry was used to analyze the differences in GMV in the structural pattern. Seed-based FC was used to analyze the functional pattern. Gaussian random field correction was used, with voxel level P < 0.001 and cluster level P < 0.05 representing statistically significant differences. Finally, the correlation between FC values and scores on the clinical characteristics assessment scale was analyzed. Results: In the GMV analysis, compared to the PD-NH group, the PD-MH group had reduced GMV in the medial superior frontal gyrus (SFGmed). In the FC analysis, the FC between the SFGmed and the left middle occipital gyrus and right calcarine sulcus decreased in the PD-MH group compared with the PD-NH group, while the FC between SFGmed and the left middle temporal gyrus increased. Correlation analysis revealed that the FC values of the SFGmed and right calcarine sulcus were correlated with the assessment scores for anxiety and sleep symptoms. The FC values of the SFGmed and left middle occipital gyrus were correlated with assessment scores for rapid eye movement disorder. Conclusion: The aberrant structure and function of the default mode network and visual processing areas seems to facilitate the generation of MH in PD, as the alteration was previously found in well-structured VH, suggesting that the two hallucinations have similar pathophysiological mechanisms.

Identification and characterization of two Isatis indigotica O-methyltransferases methylating C-glycosylflavonoids.

Isatis indigotica accumulates several active substances, including C-glycosylflavonoids, which have important pharmacological activities and health benefits. However, enzymes catalyzing the methylation step of C-glycosylflavonoids in I. indigotica remain unknown. In this study, three O-methyltransferases (OMTs) were identified from I. indigotica that have the capacity for O-methylation of the C-glycosylflavonoid isoorientin. The Type II OMTs IiOMT1 and IiOMT2 efficiently catalyze isoorientin to form isoscoparin, and decorate one of the aromatic vicinal hydroxyl groups on flavones and methylate the C6, C8, and 3'-hydroxyl positions to form oroxylin A, wogonin, and chrysoeriol, respectively. However, the Type I OMT IiOMT3 exhibited broader substrate promiscuity and methylated the C7 and 3'-hydroxyl positions of flavonoids. Further site-directed mutagenesis studies demonstrated that five amino acids of IiOMT1/IiOMT2 (D121/D100, D173/D149, A174/A150R, N200/N176, and D248/D233) were critical residues for their catalytic activity. Additionally, only transient overexpression of Type II OMTs IiOMT1 and IiOMT2 in Nicotiana benthamiana significantly increased isoscoparin accumulation, indicating that the Type II OMTs IiOMT1 and IiOMT2 could catalyze the methylation step of C-glycosylflavonoid, isoorientin at the 3'-hydroxyl position. This study provides insights into the biosynthesis of methylated C-glycosylflavonoids, and IiOMTs could be promising catalysts in the synthesis of bioactive compounds.

[Enzymatic characterization of lignan glucosyltransferase of Isatis indigotica].

The lignan glycosyltransferase UGT236(belonging to the UGT71 B family) from Isatis indigotica can catalyze the production of phloridzin from phloretin in vitro. UGT236 shares high identity with P2'GT from apple. In this study, the recombinant plasmid pET28 a-MBP-UGT236 was transferred into Escherichia coli Rosetta(DE3) cells and induced by isopropyl-ß-D-thiogalactoside(IPTG). The purified UGT236 protein was used for enzymatic characterization with phloretin as substrate. The results showed that UGT236 had the optimal reaction temperature of 40 ℃ and the optimal pH 8(Na_2HPO_4-NaH_2PO_4 system). The UGT236 activity was inhibited by Ni~(2+) and Al~(3+), enhanced by Fe~(2+), Co~(2+), and Mn~(2+), and did not affected by Mg~(2+), Ca~(2+), Li~+, Na~+, or K~+. The K_m, K_(cat), and K_(cat)/K_m of phloretin were 61.03 µmol·L~(-1), 0.01 s~(-1), and 157.11 mol~(-1)·s~(-1)·L, and those of UDPG were 183.6 µmol·L~(-1), 0.01 s~(-1), and 51.91 mol~(-1)·s~(-1)·L, respectively. The possible active sites were predicted by homologous modeling and molecular docking. By mutagenisis and catalytic activity detection, three key active sites, Glu391, His15, and Thr141, were identified, while Phe146 was related to product diversity. In summary, we found that the lignan glycosyltransferase UGT236 from I.indigotica could catalyze the reaction of phloretin into phloridzin. Several key amino acid residues were identified by structure prediction, molecular docking, and site-mutagenesis, which provided a basis for studying the specificity and diversity of phloretin glycoside products. This study can provide a reference for artificially producing glycosyltransferase elements with high efficiency and specific catalysis.

Gait Analysis with Wearables Is a Potential Progression Marker in Parkinson's Disease.

Gait disturbance is a prototypical feature of Parkinson's disease (PD), and the quantification of gait using wearable sensors is promising. This study aimed to identify gait impairment in the early and progressive stages of PD according to the Hoehn and Yahr (H-Y) scale. A total of 138 PD patients and 56 healthy controls (HCs) were included in our research. We collected gait parameters using the JiBuEn gait-analysis system. For spatiotemporal gait parameters and kinematic gait parameters, we observed significant differences in stride length (SL), gait velocity, the variability of SL, heel strike angle, and the range of motion (ROM) of the ankle, knee, and hip joints between HCs and PD patients in H-Y Ⅰ-Ⅱ. The changes worsened with the progression of PD. The differences in the asymmetry index of the SL and ROM of the hip were found between HCs and patients in H-Y Ⅳ. Additionally, these gait parameters were significantly associated with Unified Parkinson's Disease Rating Scale and Parkinson's Disease Questionnaire-39. This study demonstrated that gait impairment occurs in the early stage of PD and deteriorates with the progression of the disease. The gait parameters mentioned above may help to detect PD earlier and assess the progression of PD.

Clinical Features in Parkinson's Disease Patients with Hyperechogenicity in Substantia Nigra: A Cross-Sectional Study.

Background: Transcranial ultrasound (TCS) can be used to reveal structural changes in the substantia nigra (SN) and is a potential tool for the early diagnosis of Parkinson's disease (PD). This study aimed to explore the relationship between substantia nigra hyperechogenicity (SNH) and the clinical features of PD patients. Methods: A total of 96 PD patients were included in our study. All patients were detected by TCS and divided into two groups: PD patients with SNH (PDSN+) and those with normal SN echogenicity (PDSN-). The Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn & Yahr stage were used to assess the extent of disease-related disability of the PD patients. Non-motor symptoms were evaluated by using several scales. The instrumented stand and walk test was performed on all subjects, and gait data were gathered using a JiBuEn gait analysis system. Results: Seventy-five PD patients were successfully assessed by TCS. We found that SNH was associated with a higher UPDRS II scores (p = 0.028). In addition, compared with PDSN- group, the PDSN+ group exhibited more severe gait impairment, including increased variability in stride length (p = 0.042), decreased heel strike angle (p = 0.017), decreased range of motion of hip joints (p = 0.031), and a more asymmetrical walking pattern (p = 0.028). Conclusion: Our study demonstrated that SNH significantly correlated with activities of daily living and gait impairment in Chinese patients with PD, suggesting the formation of SNH might be a dynamic biomarker reflecting disease severity.

Functional Characterization of UDP-Glycosyltransferases Involved in Anti-viral Lignan Glycosides Biosynthesis in Isatis indigotica.

Isatis indigotica is a popular herbal medicine with its noticeable antiviral properties, which are primarily due to its lignan glycosides such as lariciresinol-4-O-ß-D-glucoside and lariciresinol-4,4'-bis-O-ß-D-glucosides (also called clemastanin B). UDP-glucose-dependent glycosyltransferases are the key enzymes involved in the biosynthesis of these antiviral metabolites. In this study, we systematically characterized the UGT72 family gene IiUGT1 and two UGT71B family genes, IiUGT4 and IiUGT71B5a, with similar enzymatic functions. Kinetic analysis showed that IiUGT4 was more efficient than IiUGT1 or IiUGT71B5a for the glycosylation of lariciresinol. Further knock-down and overexpression of these IiUGTs in I. indigotica's hairy roots indicates that they play different roles in planta: IiUGT71B5a primarily participates in the biosynthesis of coniferin not pinoresinol diglucoside, and IiUGT1 primarily participates in the biosynthesis of pinoresinol diglucoside, while IiUGT4 is responsible for the glycosylation of lariciresinol and plays a dominant role in the biosynthesis of lariciresinol glycosides in I. indigotica. Analysis of the molecular docking and site-mutagenesis of IiUGT4 have found that key residues for its catalytic activity are H373, W376, E397, and that F151 could be associated with substrate preference. This study elucidates the biosynthetic route of anti-viral lignan glycosides in I. indigotica, and provides the foundation for the production of anti-viral lignan glycosides via synthetic biology under the heterologous model.

Elevation of Plasma Homocysteine and Minor Hallucinations in Parkinson's Disease: A Cross-Sectional Study.

Purpose: Minor hallucinations (MHs) are the most common psychotic phenomena in Parkinson's disease (PD), and it has important clinical and prognostic implications in PD. Plasma homocysteine (Hcy) has been reported to predict the outcome of PD; whether or not Hcy is associated with MH is not known. We aim to investigate the Hcy level and related factors in patients with PD and MH. Methods: We conducted a cross-sectional study and included 99 patients with PD, 34 with MH, and 65 without any hallucinations. The clinical and demographic data of the patients with and without hallucinations were compared. Hcy-related clinical factors were also analyzed. Results: The plasma Hcy level was higher in MH patients than in patients without hallucinations, and the result was more pronounced in male patients than in female patients. Differences were also observed when the groups were divided on the basis of levodopa equivalent daily dose and disease duration. The high Hcy concentration was correlated with some symptoms in patients with MH, including motor dysfunction and nonmotor symptoms, such as symptoms of the gastrointestinal tract, angiocarpy, sleep/fatigue, and poor visuospatial/executive function. Conclusions: Results indicated a higher plasma Hcy concentration in MH patients than in their counterparts and revealed that Hcy is associated with certain motor and nonmotor symptoms in patients with MH. Hcy may be a marker of MH and have important therapeutic implications in PD.

[Cloning and functional characterization of lignan glycosyltransferase gene IiUGT349 in Isatis indigotica].

Based on the transcriptome data of Isatis indigotica, a total of 110 putative glycosytransferases were identified. Through prokaryotic expression and enzymic activity assay in vitro, a novel lignan glycosyltransferase gene was screened out and named IiUGT349, which catalyzed lariciresinol into lariciresinol-4-O-ß-D-glucoside and lariciresinol-4'-O-ß-D-glucoside. Bioinformatics analysis suggested that IiUGT349 contained an open reading frame(ORF) of 1 401 bp encoding a protein of 467 amino acids. A protein analysis indicated that IiUGT349 have a predecited molecular weight of 52.77 kDa and pI of 5.96. Phylogenetic analysis showed that IiUGT349 belonging to UGT90 family shared low amino acid sequence identity with the reported lignan glycosyltransferases, which may represent a novel type of lignan glycosyltransferases. Quantitative real-time PCR(qRT-PCR) analysis showed that IiUGT349 was expressed in roots, stems, young leaves and leaves, with the highest expression level in stems. Further biochemical analysis showed that the optimal reaction time of IiUGT349 recombinant protein was 12 h and the optimal temperature was 45 ℃. Subcellular localization demonstrated that IiUGT349 was located in the cytoplasm and nucleus of plants. In this study, a new glucosyltransferase gene IiUGT349 from I. indigotica belonging to the UGT90 family was cloned, which laid a foundation to further investigate its' function and elucidate the lignan glycosides biosynthesis pathway and plays an important role for great significance for the synthetic biology of active lignan glycosides.

Probiotic Supplements: Hope or Hype?

Probiotic bacteria have been associated with various health benefits and included in overwhelming number of foods. Today, probiotic supplements are consumed with increasing regularity and record a rapidly growing economic value. With billions of heterogeneous populations of probiotics per serving, probiotic supplements contain the largest quantity of probiotics across all functional foods. They often carry antibiotic-resistant determinants that can be transferred to and accumulate in resident bacteria of the gastrointestinal tract and risk their acquisitions by opportunistic pathogens. While the health benefits of probiotics have been widely publicized, this health risk, however, is underrepresented in both scientific studies and public awareness. On the other hand, the human gut presents conditions that are unfavorable for bacteria, including probiotics. It remains uncertain if probiotics from supplements can tolerate acids and bile salts that may undermine their effectiveness in conferring health benefits. Here, we put into perspective the perceived health benefits and the long-term safety of consuming probiotic supplements, specifically bringing intolerance to acids and bile salts, and the long-standing issue of antibiotic-resistant gene transfer into sharp focus. We report that probiotics from supplements examined in this study have poor tolerance to acids and bile salts while also displaying resistance to multiple antibiotics. They could also adapt and gain resistance to streptomycin in vitro. In an environment where consuming supplements is considered a norm, our results and that of others will put in perspective the persisting concerns surrounding probiotic supplements so that the current hype does not overpower the hope.