INTRODUCTION
Bariatric surgeries (BSs) are methods of weight reduction in individuals with morbid obesity otherwise resistant to lifestyle modifications and medications.1 Volunteering for these surgeries with no medical indications, with cosmetic purposes, has also substantially contributed to the rise in popularity of BS. No matter the objective, these operations are accompanied by a plethora of side effects, including alterations in body composition, especially in the form of muscle mass and muscle strength loss.2 Muscular atrophy is associated with weak prognostics in multiple diseases, including infectious diseases, organ failures, and unhealthy aging.3 Moreover, muscle mass loss is associated with lowered basic metabolism, impaired functional capacity, and weakened quality of life.4
Various methods have been examined to minimize the unwanted lean mass loss following BSs. Interventions in the form of physical exercise, namely aerobic and resistance training (RT), have been shown to improve both upper and lower limb muscle strength following restrictive and bypass surgeries.5 Also, supplementation with probiotics has been shown to preserve muscle mass and improve global muscle strength following these surgeries, with contrasting results on other body compartments.6 In fact, BSs have been observed to alter gut microbiome. For instance, there is some evidence that the production of short-chain fatty acids (SCFAs) is reduced following both Roux-en-Y gastric bypass or gastric sleeve—as an indication of dysbiosis.7 Other studies have claimed that BSs ameliorate the dysbiosis associated with obesity, signifying this change as the mediatory pathway to explain reduced risk of comorbidities following surgical interventions.8 Given these contradictions, there is some ambiguity regarding the impact of intervention with probiotics on adverse lean/muscle mass alterations observed after BSs.
Despite the growing body of evidence supporting the independent benefits of RT and probiotic supplementation following BS,5,6 the potential synergistic impact of these interventions on muscle mass preservation has remained largely unexplored. Bariatric procedures are known to significantly alter the composition and function of the gut microbiota,7,8 potentially contributing to postoperative muscle atrophy through mechanisms involving impaired SCFA production, inflammation, and disrupted metabolic signaling. Probiotic supplementation may modulate the gut–muscle axis and improve host metabolism, while RT exerts anabolic effects on skeletal muscle and enhances physical performance.5 To date, no randomized controlled trial (RCT) has comprehensively investigated the combined effects of these two interventions on muscle mass retention and related functional outcomes in patients recovering from BS.
This lack of integrated evidence provides the foundation for our novel approach to muscle mass retention and related functional outcomes in BS patients in the current RCT.
The present RCT aims to investigate the effects of three types of intervention: probiotic supplementation, physical exercise, and their combination, not only on muscle mass retention but also on a broad range of anthropometric, biochemical, metabolic, inflammatory, and functional indicators in patients with recent BS.
METHODS
Study design
The present study describes a four-arm, parallel-group, randomized, partial double-blind, placebo-controlled trial with a 2×2 factorial design conducted at health clinics affiliated with Shiraz University of Medical Sciences (Shiraz, Iran), in accordance with the Declaration of Helsinki and good clinical practice guidelines. The study protocol was reviewed and approved by the Ethics Committee of Shiraz University of Medical Sciences (IR.SUMS.MED.REC.1402.421) and registered with the Iranian Registry of Clinical Trials (IRCT20231231060581N1). The study protocol was fully explained to all participants, and written informed consent was obtained before enrollment.
Study population
Participants aged 18 years and older, diagnosed with obesity and having undergone BS within the past month, were recruited for the study. This timeframe was selected based on clinical guidelines emphasizing the importance of early postoperative monitoring for nutritional status and body composition recovery, particularly muscle mass preservation, following the first month of surgery.9 Participants were excluded if they had any of the following conditions: cardiovascular disorders, systolic or diastolic hypertension, uncontrolled metabolic disorders, neuromuscular or rheumatologic diseases, acute pulmonary embolism, symptomatic chronic heart failure, or any physical or mental disabilities. Individuals with gastrointestinal (GI) conditions (e.g., irritable bowel syndrome, inflammatory bowel disease, celiac disease, or other chronic GI disorders) were also excluded due to the potential influence of GI disorders on gut microbiota and nutrient absorption.
Individuals with allergies to milk protein, lactose, or gluten were also excluded. Additional exclusion criteria included the use of nutritional supplements, prebiotics, or probiotics within 1 month prior to the study.
Participants were withdrawn from the study if they: (1) declined to continue participation for any reason; (2) experienced any postoperative complications; (3) failed to consume at least 80% of the prescribed interventions and recommendations; (4) missed scheduled follow-up visits; (5) developed a specific illness or became pregnant during the study; (6) initiated the use of probiotic or prebiotic supplements during the study; or (7) were hospitalized for any medical condition.
Sample size
The RCT calculated sample size using G-power software version 3.1.9.4 (Heinrich Heine University), based on similar previous studies10 with a focus on skeletal muscle mass (SMM) as the primary outcome. An effect size of d=0.26, a significance level (α) of 0.05, and a statistical power of 80% (1-β error) were assumed. Based on these parameters, the sample size was initially calculated as 48 participants (12 participants per group).
To account for a potential dropout rate, the final sample size was adjusted to 52 participants (13 participants per group), ensuring adequate power for statistical analysis.
Randomization and blinding
The random allocation sequence was generated using a computer-based block randomization method (block size=4) by an independent statistician who was not involved in any other aspect of the study. Group assignments were concealed in sequentially numbered, opaque, sealed envelopes, which were opened only after participant enrollment. Participants were randomly allocated in a 1:1:1:1 ratio to four parallel groups (n=13 per group): group A (RT combined with fortified yogurt [RT+FY]), group B (FY11), group C (RT), and group D (control group receiving plain low-fat yogurt).
Participants in the yogurt groups were blinded to the type of yogurt, with fortified and plain yogurts provided in identical containers. Moreover, the independent statistician was blinded to group allocations to minimize selection bias. Participants in the exercise groups, however, were necessarily aware of their activity assignments due to the nature of the intervention.
In the present study, partial double-blinding was employed, as full blinding was impractical due to the overt nature of the exercise intervention and the required involvement of researchers in administering and supervising training sessions.
Intervention
Characteristics of interventions across study groups are summarized in Table 1. Participants in the RT+FY group consumed 120 g/day fortified low-fat yogurt containing Bacillus coagulans and Lactobacillus plantarum (1010 colony-forming unit [CFU]/g) and engaged in a supervised RT program using elastic bands for 15 to 30 minutes per day over 12 weeks. The FY group received the same FY (120 g/day) without an exercise intervention, while the RT group underwent the identical exercise program without yogurt consumption.
The placebo group consumed 120 g/day plain low-fat yogurt and did not receive additional interventions.
In the RT and RT+FY groups, a structured RT regimen targeting both upper and lower extremities was implemented using elastic bands (TheraBand; Performance Health). Exercises included shoulder press, biceps curl, lateral raise, seated row, squats, and leg extensions, performed in sessions lasting 15 to 30 minutes. The program began with one set of 10 to 12 repetitions per exercise during the first week.
Thereafter, the number of sets was gradually increased every 2 weeks based on participants’ tolerance and the exercise specialist’s evaluation. To monitor and guide exercise intensity, the Borg rating of perceived exertion (RPE) scale was used,12 with participants instructed to aim for a moderate intensity (RPE 12–14) in each session. This combined approach ensured individualized progression and safe training loads aligned with participants’ functional capacity and recovery.
Abdominal exercises were deliberately excluded to prevent strain on the surgical area post-BS. Exercise sessions were conducted under the supervision of an exercise specialist through real-time online monitoring, according to practical guidelines for post-bariatric patients.13
The two types of yogurts—FY for the FY and RT+FY groups and plain low-fat yogurt for the control group—were manufactured by Zarin Ghazal Dairy Industries Co. (DAITY). The yogurts’ color, appearance, smell, and taste were identical to ensure participants could not distinguish between them.
Throughout the intervention period, participants were instructed to include yogurt as part of their daily meals. Yogurt was chosen for fortification due to its acceptability, nutritional benefits, affordability, and palatability.14,15
As detailed in Supplementary Table 1, the nutritional composition of the yogurts was consistent across groups, with the only difference being the probiotic content. The FY contained 1010 CFU/g of B. coagulans and L. plantarum (Chr. Hansen).
Microbiological analysis demonstrated the concentration and stability of the probiotic strains throughout the study period. The selection of probiotic strains, dosage, and intervention duration was determined by previous studies reporting favorable health outcomes.16-18
Compliance and adherence monitoring
Compliance was tracked using weekly self-reported intake logs, and participants were instructed to return empty yogurt containers during their scheduled weekly appointments. In addition, automated daily reminders via text messaging were employed to support consistent yogurt consumption.
For those assigned to RT groups, the exercise sessions were supervised live through video calls on WhatsApp (Meta Platforms Inc.). This mode of delivery enabled the exercise specialist to observe participants in real time, offer corrective feedback, and tailor training to individuals’ functional capacity and progression. The interactive nature of these sessions facilitated greater engagement and safety monitoring.
In groups that consumed yogurt (either fortified or plain), a nutritionist ensured proper consumption of the yogurt by reviewing weekly checklists, and a physician addressed any reported side effects, especially GI disturbances. Participants were withdrawn if they consumed less than 80% of the prescribed yogurt or attended fewer than 80% of exercise sessions.
Primary and secondary outcomes
In the present study, the primary outcomes were SMM and muscle strength, while other outcomes of interest were classified as secondary.
Demographic assessment
At baseline, participants completed a detailed questionnaire designed to collect key demographic data, including age, educational attainment, marital status, employment status, existing health conditions, and the specific type of BS undergone (laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass).
Body composition assessment
All anthropometric and body composition evaluations were carried out under consistent conditions by trained staff during morning hours. Participants wore light clothing and no footwear during assessments.
Body weight was obtained using a precision digital scale (Seca; Seca GmbH) with 0.1 kg accuracy, following an overnight fast and after bladder emptying. Standing height was measured with a stadiometer (Seca) to the nearest 0.1 cm, while participants stood upright, barefoot, and with their heads in the Frankfurt plane. Body mass index (BMI) was determined by dividing weight (kg) by height squared (m²).
Waist circumference (WC) was measured at the midpoint between the last palpable rib and the iliac crest, using a non-stretchable tape. The tape was positioned horizontally and measurements were taken at the end of a normal exhalation, with participants standing relaxed. Hip circumference was measured around the fullest part of the buttocks, with participants standing straight and feet together.
Body composition indicators including fat percentage, visceral fat level, fat-free mass percentage, SMM, and basal metabolic rate (BMR) were assessed using a multi-frequency segmental bioelectrical impedance analyzer (Tanita BC-418; Tanita Corporation). Participants were instructed to avoid eating, drinking, and exercising for at least 2 to 4 hours prior to measurement.19 During the procedure, participants stood barefoot on the device’s electrodes and held hand grips, following the manufacturer’s positioning guidelines.
Muscle strength assessment
Maximal handgrip strength was measured using a hand dynamometer, following the Southampton protocol.20 Participants sat on a standard chair with their feet flat on the floor, shoulders in a neutral position, and elbows bent at a 90° angle. The wrist was kept neutral, with the thumb facing upwards. Participants were instructed to exert maximum force on the dynamometer for a duration of 3 seconds.
The assessment was repeated three times using the dominant hand, and the highest reading from the three trials was recorded as the final handgrip strength value.
The 30-second chair stand test (30CST) was employed to assess lower body strength and functional capacity.21 Participants sat on a standardized armless chair (seat height, 45 cm) with feet positioned shoulder-width apart and arms crossed over their chest. After receiving verbal instructions and completing a practice trial of 10 repetitions, participants were asked to complete as many full sit-to-stand cycles as possible within 30 seconds. Any movement that surpassed half of a cycle at the test’s conclusion was counted as a full repetition.
Two trials were conducted, with a 60-second rest period between them, and the best performance was used for analysis.
Assessment of dietary intake and physical activity
At both the baseline and conclusion of the intervention, a registered dietitian assessed participants’ dietary intake using a 3-day food recall method, which included 2 weekdays and 1 weekend day.22 Recorded food data were converted into grams using standard household measurement tools, and the energy and nutrient content was quantified through Nutritionist 4 software (First Databank Inc.). Participants were instructed to maintain their regular diets during the study intervention.
Although both groups participated in structured exercise interventions, physical activity levels were assessed at two time points using the International Physical Activity Questionnaire Short Form (IPAQ-SF). This was essential for a comprehensive evaluation of participants’ total physical activity, including both exercise and non-exercise activities, as physical activity beyond prescribed exercise influences energy expenditure and health outcomes. The IPAQ-SF includes seven items to assess intensity (light, moderate, or vigorous) and duration (in minutes) of activity throughout the week, thus providing a standardized metric of activity beyond prescribed exercise.23 Results were expressed as metabolic equivalent of task (MET) minutes per week, a widely accepted measure of energy expenditure, allowing for a more nuanced understanding of the role of physical activity in each intervention.
Biochemical assessment
Following an overnight fasting period of 8–10 hours, a 6 mL venous blood sample was collected from each participant. The samples were centrifuged at 3,500 g for 3 minutes to separate the serum, which was subsequently aliquoted and stored at −80 °C until the time of analysis.
Fasting blood glucose, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) concentrations were determined using enzymatic colorimetric methods with commercially available assay kits (Pars Azmun Co.) and analyzed by an automated biochemistry analyzer (BT-1500; Biotecnica Instruments). Serum insulin levels were quantified using a human-specific enzyme-linked immunosorbent assay (ELISA) kit (Monobind Inc.).
High-sensitivity C-reactive protein (hs-CRP) concentrations were measured using a commercial ELISA kit (Diagnostics Biochem Canada). Malondialdehyde (MDA) levels, as a marker of lipid peroxidation, were determined using the thiobarbituric acid reactive substances (TBARS) method with a colorimetric assay kit (ZellBio GmbH). Total antioxidant capacity (TAC) was determined using the ferric reducing antioxidant power (FRAP) method, with a colorimetric assay kit from ZellBio GmbH.
Hepatic enzyme activities, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT), were evaluated using ELISA kits (Greiner Bio-One), according to manufacturer protocols.
Serum cortisol levels were measured by a competitive ELISA method employing a commercially available kit (DRG Instruments GmbH). Serum adiponectin concentrations were determined using a sandwich ELISA kit (BioVendor). The concentration of 25-hydroxyvitamin D (25(OH)D) in serum samples was assessed via a direct ELISA kit (Euroimmun) in accordance with the manufacturer’s instructions.
Depression assessment
The severity of any depression in participants was evaluated using the Beck Depression Inventory-II (BDI-II), a widely utilized self-reported questionnaire.24 The validity and reliability of the Persian version of this tool have been previously confirmed in Iranian populations.25 The BDI-II consists of 21 items, with total scores ranging from 0 to 63. Based on the total score for depressive symptoms, individuals are categorized into the following levels of depression: 0–10 (minimal or no depression), 11–16 (mild), 17–20 (requires psychiatric consultation), 21–30 (moderate), 31–40 (severe), and above 40 (very severe depression).
Statistical analyses
All statistical analyses were conducted using IBM SPSS Statistics version 21 (IBM Co.). The normality of continuous variables was assessed using the Kolmogorov–Smirnov test. Because data were normally distributed, parametric tests were used for further analyses.
Descriptive statistics are reported as mean±standard deviation for continuous data and as frequencies (percentages) for categorical variables. Between-group comparisons at baseline were carried out using one-way analysis of variance (ANOVA) for continuous variables and chi-square tests for categorical variables. Within-group differences from baseline to the end of the intervention were evaluated using paired t-tests.
To assess the effects of interventions, change scores (post-intervention minus baseline values) were calculated for each outcome. The baseline characteristics were compared across the four groups using one-way ANOVA. When overall group differences were detected, pairwise comparisons were performed using Tukey’s least significant difference post hoc test.
Analysis of covariance (ANCOVA) was applied to compare dietary intake variables between groups, with total energy intake included as a covariate. Additionally, ANCOVA was used to evaluate the effectiveness of the interventions, adjusting for potential confounders that significantly differed at baseline, including educational attainment, visceral fat percentage, serum insulin, and serum 25(OH)D levels. All analyses were conducted based on a per-protocol approach, as no participants had missing data and all participants completed the study according to the protocol.
For all analyses, a two-sided P-value less than 0.05 was considered statistically significant.
RESULTS
Among 115 individuals assessed for eligibility, 52 met the inclusion criteria and were randomized equally into four groups: RT+FY group, FY group, RT group, and placebo (13 participants per group). No participants were lost to follow-up. All randomized individuals completed the study and were included in the final analysis (Fig.
1).
Baseline characteristics of participants across the study groups are presented in Table 2. No significant differences were observed among the groups regarding age, sex distribution, marital status, employment, anthropometric indices, or most biochemical and functional parameters (P>0.05). However, significant differences were detected in educational attainment (P=0.007), with a higher proportion of participants holding diplomas or higher degrees in the FY group.
Additionally, significant between-group differences were noted in visceral fat percentage (P=0.002), serum insulin levels (P=0.004), and serum 25(OH)D concentrations (P=0.001).
Table 3 presents changes in physical activity levels and dietary intake variables across the four study groups over the intervention period. Physical activity, measured in MET-minutes per week, showed a statistically significant difference between groups (P<0.001). Participants in the RT+FY group exhibited the highest increase (814.77±250.49 MET-min/week), followed closely by the RT group (861.38±348.97 MET-min/week).
In contrast, the FY and control groups demonstrated notably smaller changes (121.06±239.1 and 235.56±445.88 MET-min/week, respectively).
No significant between-group differences were observed for changes in daily energy intake (P=0.767) or macronutrient intake, including carbohydrates (P=0.927), protein (P=0.779), fat (P=0.294), and fiber (P=0.107). While the RT group showed a slight increase in carbohydrate and fat intake, the FY group exhibited reductions across most macronutrient categories. Regarding micronutrients, no statistically significant differences were detected between groups in the intake of cholesterol (P=0.187), saturated fatty acids (P=0.259), monounsaturated fatty acids (P=0.332), or polyunsaturated fatty acids (P=0.551).
Moreover, changes in vitamin and mineral intakes, including vitamins B1, B3, B6, B9, B12, A, D, E, and C, as well as magnesium and zinc, also did not differ significantly among groups (P>0.05).
The effects of the interventions on anthropometric, metabolic, inflammatory, and functional variables are summarized in Table 4. Significant reductions in weight, BMI, WC, waist-to-hip ratio (WHR), body fat percentage (BFP), and visceral fat percentage were observed within all groups over the study period (all intragroup P-values <0.001). However, between-group comparisons showed no significant differences in these anthropometric measures (P>0.05).
Fat-free mass percentage (P=0.001) and BMR (P=0.003) differed significantly between groups, with the RT+FY group showing relatively smaller declines in fat-free mass percentage and BMR in comparison to the other groups.
In terms of changes in SMM, the RT+FY group showed the smallest reduction in comparison to the other groups (P<0.001). The RT group, FY group, and control group experienced larger reductions in SMM, with statistically significant changes within each group. Functional outcomes related to muscle strength, including hand grip strength (P=0.038) and 30CST repetitions (P<0.001), improved significantly across all intervention groups except for the control.
The RT+FY group showed the most pronounced improvements in these parameters.
Among inflammatory and oxidative stress markers, hs-CRP levels decreased significantly in the RT+FY and FY groups, with a notable between-group difference (P=0.004). MDA levels tended to decrease, particularly in the RT+FY group, although the between-group difference did not reach statistical significance (P=0.080). TAC showed no significant between-group differences (P=0.820).
Metabolic markers, including fasting blood sugar (FBS), improved significantly within groups; however, between-group differences were not statistically significant (P=0.787). Changes in insulin levels and lipid profiles (TG, TC, LDL-C, and HDL-C) varied within groups but did not differ significantly across groups (all P>0.05). Liver enzymes (ALT, AST, and GGT) and cortisol levels showed minor changes without significant between-group differences.
Notably, adiponectin levels increased significantly in the RT+FY and FY groups, but the between-group comparison was not significant (P=0.308). Moreover, serum 25(OH)D concentrations (P=0.235) and depression scores (P=0.769) showed within-group changes, although no significant between-group differences were detected.
DISCUSSION
The present RCT provides some novel evidence regarding the impact of probiotics, RT, and their combination on the prevention of adverse effects in patients with BSs. We observed some improvements in body fat deposits across all participant groups, indicated by reductions in several indices/measurements, including weight, BMI, WC, WHR, BFP, and visceral fat. As expected, a level of protein loss was also observed, evident by reductions in fat-free mass percentage and SMM.
Notably, we found that the group of patients with combined intervention (FY+RT) had the greatest potential to minimize negative impacts of BS in comparison to participant groups with other interventions/the control. Moreover, interventions with probiotics, RT, and the combination thereof had similar impacts on indicators of functionality—namely, handgrip and chair stand tests. These improvements were not observed in the no-intervention control.
There is some evidence of the impact of BSs on gut microbiota. Evidence from human studies and animal models following BSs indicates an increase in Akkermansia spp. (phylum Verrucomicrobia), along with overall increases in the Bacteroidetes and Proteobacteria phyla and a concomitant decrease in Firmicutes.26 Regardless of the potential dysbiosis caused by BSs, the effectiveness of intervention with probiotics is controversial.
In an RCT format, Ghafouri-Taleghani et al.27 investigate the impact of probiotics supplementation in patients with food addiction and weight regain after undergoing BSs. The RCT reports significant improvements in BMI and fat mass in the intervention group, as well as in eating behavior, food addiction, leptin, and oxytocin levels. In contrast, a study by Zhang et al.28 does not detect any meaningful impact on BMI, excess weight loss, or C-reactive protein in post-surgery patients due to intervention with probiotics.
The study does report a significant impact on WC following intervention with probiotics. Research by Potrykus et al.29 investigates the impact of preoperative administration of probiotics on anthropometric and biochemical measurements/indices at 1-, 3-, and 6-month follow-up points post-surgery. Consistent with other findings, their work does not report any additional benefits for preoperative probiotics in patient outcomes.
Given existing evidence on the efficacy of probiotics in improving anthropometric and body composition outcomes together with findings from the present study—specifically, the suggestion of no extra benefits of probiotics in terms of excess body weight/fat distribution—it can be hypothesized that these improvements cannot be further augmented via intervention with probiotics following BSs.
The impact of probiotic administration on protein/muscle retainment has been established. Even a ‘gut/microbiome-muscle axis’ has been hypothesized to explain the effects. Several mechanisms have been postulated to elucidate the pathway.
Probiotics—with varying degrees of effect depending on the species being supplemented—enhance the production of SCFAs, namely propionate, acetate, and butyrate acids.30 These elements have been associated with the regulation of multiple metabolic agents, including glucose uptake by muscle cells. This effect is believed to be mediated through enhancing the production of incretins, most importantly glucagon-like peptide 1 (GLP-1) which is known to improve insulin sensitivity.31
Improved glucose uptake by muscle cells might be responsible for the reduced muscle loss and improved functionality observed in the intervention models of the present study. Moreover, we observed that the preservation of muscle mass—as indicated by smaller reductions in fat-free mass and SMM—was more pronounced with administration of the combination of FY and RT. Interestingly, the decline in BMR, a marker of overall metabolic function and energy expenditure, was also less significant in the intervention groups, particularly in the FY+RT group.
This may reflect a better retention of metabolically active tissue and improved energy regulation following the combined intervention. The effect of RT on glucose metabolism, both directly and indirectly through GLP-1, is well established.32 Hence, we propose that the muscle-retaining impact of RT is significantly augmented when accompanied with casual enrichment of diet with food probiotics. Nonetheless, we were not able to detect any differential impact of any treatment on FBS or insulin, thus maintaining speculation on the exact mechanisms through which the effects could be described.
Both physical exercise and probiotics have been shown to positively alter the oxidative/inflammatory status of the body, especially in the catabolic phase following a major surgery.33 Probiotics inhibit the production of lipopolysaccharide by pathogenic bacteria which induces the expression of pro-inflammatory cytokines/agents, such as nuclear factor-kappa B (NF-κB) via attachment to Toll-like receptor 4 (TLR4).34 The inflammatory cascade is then responsible for muscular atrophy, both directly through modulation of intramuscular pathways—including NF-κB, Janus-activated kinase/signal transducer and activator of transcription (JAK/STAT), and p38 mitogen-activated protein kinase (MAPK)—and indirectly via modification of the hypothalamic-pituitary-adrenal (HPA) axis and fat metabolism. Increased levels of post-surgical oxidative stress and inflammation have been established.35 Our findings suggest that both the combined intervention (RT+FY) and intervention with FY are effective in reducing hs-CRP levels as an indicator of the inflammatory state. However, we could not ratify a clear differential impact on indices of oxidative stress—with the combination treatment being the only effective method on reducing MDA levels, in contrast to an inconsistent pattern observed regarding TAC.
We therefore suggest that even though a clear mechanistic explanation cannot be formulated through the impact of probiotics and physical exercise on inflammatory/oxidative status following BSs with regard to observed muscle preservation effects, supplementation with probiotics is more likely to play a bigger role than physical exercise.
Adiponectin is an adipokine secreted by the adipose tissue to suppress excess intake and induce satiety.36 Even though the impact of physical activity is evident on augmenting the secretion of and sensitivity to this hormone,37 the effects of probiotics on adiponectin are far less studied and are inconsistent.38,39 Adiponectin has been shown to be involved in skeletal muscle health, mainly through its impact on insulin sensitivity and glucose uptake regulation by muscle fibers. We observed that the interventions of combined treatment and FY alone are the only interventions with meaningful effects on adiponectin levels. Given the discrepancies between findings of the current study and the existing literature, further data is needed to reach an unequivocal conclusion about the effects of probiotics and physical exercise on adiponectin levels in patients following BSs.
The present RCT is unprecedented in its attempt to investigate the impact of the combined effects of physical exercise and probiotic-enriched food on muscle loss observed following BSs. Nonetheless, the findings of the present study need to be regarded in light of certain limitations. First, the impact of interventions might differ based on the type of surgery conducted—i.e., bypass vs. restrictive methods.40 Such differential impact could not be distinguished owing to the limited number of willing participants.
Second, bioelectrical impedance analysis estimations of body compartments, as opposed to imaging gold standard methods—e.g., dual-energy X-ray absorptiometry suffice as measurement in the present RCT. Finally, even though multiple indicators were measured in an attempt to explain observed effects, some observations remained ambiguous with regard to their mechanistic justifications.
The findings of this RCT suggest that a combined intervention involving RT and FY may be an effective strategy to mitigate muscle-wasting effects commonly observed in patients after BSs. This approach appeared to better preserve muscle mass, maintain metabolic function—as indicated by a less pronounced decline in BMR—and improve muscle strength in comparison to either intervention alone or no intervention. Despite these promising results, the underlying mechanisms responsible for the observed effects remain to be fully elucidated.
Furthermore, inconsistencies with findings in previous literature, along with certain methodological limitations, warrant cautious interpretation of our results. Future research should aim to explore the mechanistic pathways by which probiotics influence muscle preservation—particularly through gut microbiota modulation, SCFA production, and inflammatory regulation. Additionally, studies with larger sample sizes are needed for stratified analyses based on type of BS (e.g., sleeve gastrectomy vs.
Roux-en-Y gastric bypass), as patients’ responses to interventions may differ depending on the surgical procedure and associated changes in nutrient absorption or gut ecology.
SUPPLEMENTARY MATERIALS
Supplementary materials can be found online at https://doi.org/10.7570/jomes25045.