Abstract

Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI -1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = -0.482; 95% CI,-0.813, -0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.

Abstract

BACKGROUND Malnutrition and metabolic alterations of cancer cachexia are often associated with negative weight loss and muscle mass wasting. In this sense, protein supplementation can be a strategy to help counteract the loss and/or maintenance of mass in these patients. The aim of this study was to evaluate the effect of leucine supplementation on body composition in outpatients with gastrointestinal tract cancer. METHODS It was a randomized, blinded, controlled, parallel trial, performed in male patients with a cancer diagnosis of the gastrointestinal tract and appendix organs undergoing chemotherapy. All the patients were allocated to one of the protocol groups: L-leucine supplement or the control group, during 8 weeks of intervention. We evaluated the body composition through bioelectrical impedance analysis, the cancer cachexia classification, and the diet intake before and after the intervention protocol. The intention-to-treat approach was performed to predict the missing values for all patients who provide any observation data. RESULTS The patients were an average age of 65.11 ± 7.50 years old. In the body composition analysis with patients who finished all the supplementation, we observed a significant gain in body weight (61.79.9 ± 9.02 versus 64.06 ± 9.45, p = 0.01), ASMM (7.64 ± 1.24 versus 7.81 ± 1.20, p = 0.02) in the Leucine group, whereas patients in the control did not present significant variation in these parameters. There was no significant intergroup difference. While in the analysis included the patients with intention-to-treat, we found a significant increase in body weight (p = 0.01), BMI (p = 0.01), FFM (p = 0.03), and ASMM (p = 0.01) in the Leucine group. No significant intergroup differences. These results also similar among cachectic patients. CONCLUSION A balanced diet enriched with free-Leucine supplementation was able to promotes gains in body weight and lean mass in older men diagnosticated with gastrointestinal and appendix organs of digestion cancer after 8 weeks. However, the fact that most men are non-cachectic or pre-cachectic is not clear if the increase in muscle mass was due to a high intake of leucine, since no difference between groups was detected. Moreover, we know that benefits on body composition are due to adequate calorie and macronutrients consumption and that balanced feeding according to nutrition Guidelines seems crucial and must be advised during the oncological treatment.

Abstract

A pathological increase in intestinal leak is implicated in age-associated muscle loss, termed sarcopenia, and reduced sarcopenia-related quality-of-life (SarQoL). However, the potential therapies remain elusive. We investigated the effects of probiotic supplementation on sarcopenia and SarQoL in geriatric older adults. We randomized sarcopenic men into placebo (age = 71.4 ± 3.9 years, n = 63) and probiotic (age = 73 ± 4.1 years, n = 60) groups for 16 weeks. The probiotic used was one capsule daily of Vivomix 112 billion for 16 weeks. We measured sarcopenia parameters of handgrip strength (HGS) and skeletal mass index (SMI), plasma zonulin (marker of the intestinal leak), and SarQoL using a targeted questionnaire. Probiotics improved the SarQoL scores for locomotion, functionality, and activities of daily living and prevented a decline in cumulative SarQoL observed in the placebo group (all p < 0.05). Probiotic supplementation also reduced plasma zonulin and marker of systemic bacterial load. These changes were accompanied by an increase in HGS and maintenance of gait speed in the probiotic group compared to the placebo group. Correlation analysis revealed significant associations of cumulative SarQoL scores with plasma zonulin and HGS in the probiotic group. Collectively, probiotics improved SarQoL and HGS by repairing pathological intestinal leak. Future studies may further dissect the relation between intestinal leak and SarQoL in older adults taking probiotics.

Abstract

BACKGROUND & AIMS The COVID-19 pandemic continues to pose unprecedented challenges to worldwide health. While vaccines are effective, additional strategies to mitigate the spread/severity of COVID-19 continue to be needed. Emerging evidence suggests susceptibility to respiratory tract infections in healthy subjects can be reduced by probiotic interventions; thus, probiotics may be a low-risk, low-cost, and easily implementable modality to reduce risk of COVID-19. METHODS In this initial study, we conducted a randomized, double-blind, placebo-controlled trial across the United States testing probiotic Lacticaseibacillus rhamnosus GG (LGG) as postexposure prophylaxis for COVID-19 in 182 participants who had household exposure to someone with confirmed COVID-19 diagnosed within ≤7 days. Participants were randomized to receive oral LGG or placebo for 28 days. The primary outcome was development of illness symptoms within 28 days of COVID-19 exposure. Stool was collected to evaluate microbiome changes. RESULTS Intention-to-treat analysis showed LGG treatment led to a lower likelihood of developing illness symptoms versus placebo (26.4 % vs. 42.9 %, p = 0.02). Further, LGG was associated with a statistically significant reduction in COVID-19 diagnosis (log rank, p = 0.049) via time-to-event analysis. Overall incidence of COVID-19 diagnosis did not significantly differ between LGG and placebo groups (8.8 % vs. 15.4 %, p = 0.17). CONCLUSIONS This data suggests LGG is associated with prolonged time to COVID-19 infection, reduced incidence of illness symptoms, and gut microbiome changes when used as prophylaxis ≤7 days post-COVID-19 exposure, but not overall incidence. This initial work may inform future COVID-19 prevention studies worldwide, particularly in developing nations where Lacticaseibacillus probiotics have previously been utilized to reduce other non-COVID infectious-morbidity. TRIAL REGISTRATION ClinicalTrials.gov, NCT04399252, Date: 22/05/2020. https://clinicaltrials.gov/ct2/show/NCT04399252.

Abstract

BACKGROUND There are complicated mechanisms that link the disruption of the gut microbiome to the symptoms and complications of polycystic ovary syndrome (PCOS). In this study, an attempt was made to assess the effects of synbiotics on the health-related quality of life (HRQoL) in women with PCOS . METHODS Fifty-six women with PCOS were enrolled in a triple-blind controlled trial for 12 weeks. They were randomly assigned to receive a daily 2-gram synbiotic sachets (containing Bacillus coagulans (GBI-30), Lactobacillus rhamnosus, Lactobacillus helveticus, and fructooligosaccharide) (n = 28) or placebo (n = 28). To evaluate the impact on the HRQoL, participants were required to fill 26-Item Polycystic Ovary Syndrome Health-Related Quality of Life Questionnaire (PCOSQ-26), 12-Item Short-Form Health Survey (SF-12) and Perceived Stress Scale (PSS-10) pre and post the intervention. RESULTS Finally, statistical analyses were performed on 52 participants who finished the trial. Synbiotic supplementation improved the scores of emotional (P = 0.044), body hair (P = 0.016), weight (P = 0.033) and infertility domains (P = 0.027) of PCOSQ-26 compared to placebo group. The physical score within SF-12 also had a significant enhancement (P = 0.035). No significant improvement was seen in the PSS-10 score at the end of the trial. CONCLUSION This study illustrated the advantageous effects of synbiotics on the health-related quality of life in women with PCOS. Further studies are required to confirm our findings. TRIAL REGISTRATION http://www.irct.ir : IRCT20211108053007N1; date of registration: 14/02/2023.

Abstract

BACKGROUND Chemotherapy is an important approach for lung cancer patients. The study was designed to evaluate the feasibility of the compound probiotic supplements in improving the quality of life for lung cancer patients undergoing chemotherapy. METHODS This randomized, double-blind, placebo-controlled trial enrolled chemotherapy-naive patients with lung cancer who were scheduled to receive platinum-based doublet chemotherapy. All eligible patients were randomly administered (1:1) compound probiotic supplements (group BP-1) or placebo (group C) for two chemotherapy cycles. The EORTC QLQ C30 questionnaire scores were evaluated before the first, second, and third cycles of chemotherapy. The primary endpoint was the difference in the EROTC QLQ C30 questionnaire score between the two groups after two cycles of chemotherapy. RESULTS A total of 110 patients were recruited from March 2021 to January 2022. After undergoing two cycles of chemotherapy, group BP-1 were significantly better in various dimensions of the overall quality of life, role function, nausea and vomiting, appetite loss, constipation, and diarrhea relative to group C (76.90 ± 18.31 vs. 58.89 ± 17.17; 93.33 ± 11.58 vs. 85.93 ± 15.06; 0.00 ± 0.00 vs. 27.04 ± 29.15; 6.67 ± 13.53 vs. 22.22 ± 18.80; 0.95 ± 5.63 vs. 28.15 ± 22.42; 2.86 ± 9.47 vs. 15.56 ± 16.82; p < 0.05, respectively). The incidence of nausea and vomiting, appetite loss, constipation, and diarrhea in group BP-1 was significantly lower than in group C (0% vs. 71.43%, 16.67% vs. 57.14%, 2.38% vs. 63.27%, and 7.14% vs. 42.86%, respectively, p < 0.001). CONCLUSIONS Compound probiotic supplements can improve the quality of life and relieve chemotherapy-related gastrointestinal side effects for lung cancer patients receiving platinum-based doublet chemotherapy. (Chinese Clinical Trial Registry: ChiCTR1800019269).

Abstract

Probiotics are exploited for adjuvant treatment in IBS, but reliable guidance for selecting the appropriate probiotic to adopt for different forms of IBS is lacking. We aimed to identify markers for recognizing non-constipated (NC) IBS patients that may show significant clinical improvements upon treatment with the probiotic strain Lacticaseibacillus paracasei DG (LDG). To this purpose, we performed a post-hoc analysis of samples collected during a multicenter, double-blind, parallel-group, placebo-controlled trial in which NC-IBS patients were randomized to receive at least 24 billion CFU LDG or placebo capsules b.i.d. for 12 weeks. The primary clinical endpoint was the composite response based on improved abdominal pain and fecal type. The fecal microbiome and serum markers of intestinal (PV1 and zonulin), liver, and kidney functions were investigated. We found that responders (R) in the probiotic arm (25%) differed from non-responders (NR) based on the abundance of 18 bacterial taxa, including the families Coriobacteriaceae, Dorea spp. and Collinsella aerofaciens, which were overrepresented in R patients. These taxa also distinguished R (but not NR) patients from healthy controls. Probiotic intervention significantly reduced the abundance of these bacteria in R, but not in NR. Analogous results emerged for C. aerofaciens from the analysis of data from a previous trial on IBS with the same probiotic. Finally, C. aerofaciens was positively correlated with the plasmalemmal vesicle associated protein-1 (PV-1) and the markers of liver function. In conclusion, LDG is effective on NC-IBS patients with NC-IBS with a greater abundance of potential pathobionts. Among these, C. aerofaciens has emerged as a potential predictor of probiotic efficacy.

Abstract

The gut microbiota is vital for human body development and function. Its development in early life is influenced by various environmental factors. In this randomized controlled trial, the gut microbiota was obtained as a secondary outcome measure in a study on the effects of one hour of daily skin-to-skin contact (SSC) for five weeks in healthy full-term infants. Specifically, we studied the effects on alpha/beta diversity, volatility, microbiota maturation, and bacterial and gut-brain-axis-related functional abundances in microbiota assessed thrice in the first year. Pregnant Dutch women (n = 116) were randomly assigned to the SSC or care-as-usual groups. The SSC group participants engaged in one hour of daily SSC from birth to five weeks of age. Stool samples were collected at two, five, and 52 weeks and the V4 region was sequenced. We observed significant differences in the microbiota composition, bacterial abundances, and predicted functional pathways between the groups. The SSC group exhibited lower microbiota volatility during early infancy. Microbiota maturation was slower in the SSC group during the first year and our results suggested that breastfeeding duration may have partially mediated this relation. Our findings provide evidence that postpartum SSC may influence microbiota development. Replication is necessary to validate and generalize these results. Future studies should include direct stress measurements and extend microbiota sampling beyond the first year to investigate stress as a mechanism and research SSC's impact on long-term microbiota maturation trajectories.

Abstract

OBJECTIVE We hypothesize that synbiotic supplementation could modulate the intestinal microbiota and subsequently, improve the condition of hypothyroid patients. METHODS Fifty-six adult hypothyroid patients were recruited to this double-blind, placebo-controlled, randomized clinical trial. The intervention was 10 weeks of synbiotic (500 mg of 109 CFU/g probiotics plus fructo-oligosaccharide, n = 28) compared to placebo (lactose, magnesium stearate, talc, and silicon dioxide, n = 28). Randomization and allocation to trial groups were carried out using random number sequences drawn from https://sealedenvelope.com/. Primary outcomes were serum thyroid stimulating hormone (TSH) and free thyroxine (FT4), and secondary outcomes were depression, quality of life, and blood pressure (BP). P-values< 0.05 were considered statistically significant. RESULTS Analysis on 51 patients who completed the trial showed that TSH and depression (p> 0.05) did not change significantly, while serum FT4 significantly increased in both groups (p = 0.03 and p = 0.02 in symbiotic and placebo respectively). A significant decrease in systolic BP occurred only in the synbiotic group (p = 0.05). Significant improvements occurred regarding different domains and areas of quality of life in the crude and adjusted analysis, including perceived mental health (p = 0.02), bodily pain (p = 0.02), general health perception (p = 0.002), and wellbeing (p = 0.002), which were significantly higher in the synbiotic group. CONCLUSIONS Ten-week supplementation with synbiotic had no favorable effect on depression and TSH, but it improved blood pressure and quality of life in patients with hypothyroidism. More trials are needed to support or reject these findings. TRIAL REGISTRATION IRCT20210926052583N1, Iranian Registry of Clinical Trials (IRCT), registered October 1st, 2021.

Abstract

Synbiotic 2000, a pre + probiotic, reduced comorbid autistic traits and emotion dysregulation in attention deficit hyperactivity disorder (ADHD) patients. Immune activity and bacteria-derived short-chain fatty acids (SCFAs) are microbiota-gut-brain axis mediators. The aim was to investigate Synbiotic 2000 effects on plasma levels of immune activity markers and SCFAs in children and adults with ADHD. ADHD patients (n = 182) completed the 9-week intervention with Synbiotic 2000 or placebo and 156 provided blood samples. Healthy adult controls (n = 57) provided baseline samples. At baseline, adults with ADHD had higher pro-inflammatory sICAM-1 and sVCAM-1 and lower SCFA levels than controls. Children with ADHD had higher baseline sICAM-1, sVCAM-1, IL-12/IL-23p40, IL-2Rα, and lower formic, acetic, and propionic acid levels than adults with ADHD. sICAM-1, sVCAM-1, and propionic acid levels were more abnormal in children on medication. Synbiotic 2000, compared to placebo, reduced IL-12/IL-23p40 and sICAM-1 and increased propionic acid levels in children on medication. SCFAs correlated negatively with sICAM-1 and sVCAM-1. Preliminary human aortic smooth-muscle-cell experiments indicated that SCFAs protected against IL-1β-induced ICAM-1 expression. These findings suggest that treatment with Synbiotic 2000 reduces IL12/IL-23p40 and sICAM-1 and increases propionic acid levels in children with ADHD. Propionic acid, together with formic and acetic acid, may contribute to the lowering of the higher-than-normal sICAM-1 levels.