Effects of probiotics on selected anthropometrics and biochemical measures in overweight or obese Saudi subjects: a double-blind, placebo-controlled, randomised clinical trial

This section may be divided by subheadings. It should provide a concise and precise description of the experimental results and their interpretation, as well as the experimental conclusions that can be drawn.

The main findings of the present study demonstrated that although multi-strain probiotic supplementation for 12 weeks among Arab adults with overweight or obesity had statistically significant effects on many anthropometric measurements, including body weight, BMI and HC, these effects were not clinically meaningful when compared with placebo, with the exception of fat intake. These findings are in opposition with Michael et al., who used a multi-strain of lactobacilli and bifidobacteria (5 × 10¹⁰ CFU). They found a significant weight reduction favouring the probiotic group after 6 months of treatment (–1·30 kg, P = 0·0001). Also, the reduction was significant in BMI (−1·5 %, P < 0·0001), WC (−0·9 %, P < 0·0001) and WHR (−1·2 %, P < 0·0001). Interestingly, the reduction was greater in individuals who were overweight (−1·9 %, −1·5 kg) than individuals with obesity (−1·2 %, −1·06 kg)⁽²⁵⁾. Additionally, in a 3-week randomised controlled trial, consumption of probiotic-fortified cheese led to a number of advantageous changes in health indicators among individuals with overweight or obesity; the reduction was larger in the probiotic group than the control group in body weight (−5·7 v. –4·4 kg, P = 0·08) and BMI (−2 v. –1·6 kg/m², P = 0·03), suggesting probiotic positive effects on metabolic disorders⁽²⁶⁾. Likewise, greater differences in body measurements were noticed for subjects who took the multi-strain probiotic (1 × 10⁹ CFU) combined with a diet than the group who only applied a diet. The decrease was in WC (P = 0·03), WHR (P = 0·02) and CI (P = 0·03)⁽²¹⁾. Furthermore, the administration of Lactobacillus gasseri SBT2055 for healthy adults revealed a significant decrease in the visceral, subcutaneous, total fat areas, body weight, BMI, WC, HC and WHR within the probiotic group and between-group comparisons at baseline and week 12, demonstrating that the inhibition of lipid absorption is a possible mechanism underlying the observed effects⁽²⁷⁾. In another randomised controlled trial, taking the probiotic Lactiplantibacillus plantarum IMC 510^® (1·5 × 10¹⁰ CFU) for 3 months led to a significant drop in body weight (P = 0·03), BMI (P = 0·03), WC (P = 0·04) and WHR (P = 0·04)⁽²⁸⁾. The favourable effects observed within the probiotic group in the present study may be attributed to probiotic supplementation, considering that a hypoenergetic diet was applied to both the probiotic and placebo groups. The lack of clinically significant effect as compared with previous findings can be attributed to ethnic groups, as different populations may exhibit varying lag time in biological response to probiotic supplementation. According to Gupta and colleagues, geographical variations in microbiome structure can significantly affect how a population responds to microbiome-based therapeutics, including probiotics⁽²⁹⁾. Additionally, based on the existing understanding of the effectiveness of probiotic supplementation in mitigating overweight and obesity, current systematic review emphasised that probiotic genus, strain, dosage, duration of supplementation and delivery matrix were known as significant factors on the anti-obesity effects of probiotics⁽³⁰⁾.

Similar to the present findings, one study assessed the effects of probiotic supplementation on weight reduction in healthy, young adult females using a 6-week supplementation with Bifidobacterium lactis BS01 and Lactobacillus acidophilus LA0 (2 × 10⁹ CFU) without involving dietary restrictions. The findings showed that the BMI decreased higher in the supplemented group after treatment (by 4·1 % compared with 0·81 % in the placebo group); however, the differences were NS. WC was elevated by 0·67 % in the supplemented group and reduced by 1·33 % in the placebo group. Changes in either group were not statistically significant. Similarly, WHR increased by 1·195 % in the supplemented group and decreased by 1·36 % in the placebo group. The effect sizes were all modest and insignificant⁽³¹⁾. Among treatment naïve subjects with type 2 diabetes, a significant improvement in WHR (P = 0·02) was observed favouring the probiotics group when compared with the placebo group, and no differences were noted in weight or BMI. However, within the group, this significant alteration was absent in weight, BMI and WHR following the administration of multi-strain probiotics over a period of 3 months⁽³²⁾. Moreover, Zarrati and colleagues used three different groups for the intervention: probiotic yogurt enriched in multi-strain Lactobacillus and Bifidobacterium with a low caloric diet (PLCD), probiotic yogurt without a low caloric diet and regular yogurt with a low caloric diet (RLCD). The results revealed that the RLCD group had a greater reduction in body weight, BMI and HC (–24·87, –21·9 and –23·18, respectively) compared with the PLCD group (–24·23, –21·55 and 21·84, respectively) after the intervention. However, all changes were NS. In contrast, among all assessed variables, only WC changes were larger in the PLCD group compared with the RLCD group (–2·78 and –2·3, respectively), although this difference was still statistically insignificant (P = 0·7)⁽³³⁾. Similarly, Omar and others reported no significant differences in body weight or fat mass at the conclusion of the study; body weight fluctuations were less than 5 %⁽³⁴⁾.

Regarding dietary intake, the probiotic group showed a significant reduction in calories compared with the baseline (–387·3 kcal/d, P = 0·002), but this reduction was not statistically significant when compared with the placebo group (–63 kcal/d, P = 0·09). This reduction is suggested to be primarily due to the decrease in fat intake (–29 %, P = 0·001) in the probiotic group, while the placebo group exhibited a 6 % reduction in fat intake (P = 0·41) compared with the baseline. Consuming excessive dietary fat not only elevates the body’s exposure to potentially pro-inflammatory free fatty acids and their derivatives but also suppresses the expression of tight junction proteins, such as zonulin and occludin, thereby increasing intestinal permeability⁽³⁵⁾. This promotes the absorption of endotoxins leading to metabolic endotoxemia. Therefore, Saudi clinical practice guideline emphasises on adopting a low-calorie diet with a targeted reduction in fat intake to less than 30 %⁽³⁶⁾. Likewise, Mahadzir et al. reported that after a 4-week period of MCP (3·0 × 10¹⁰ CFU) consumption, the same product of this study, the subjects in the probiotic group exhibited a significant decrease (P = 0·04) in their energy consumption, roughly 300 kcal/d, in comparison with their initial intake levels⁽³⁷⁾. Additionally, the reduction in food intake was also noticed in the Canadian study, but it was non-significant; however, the energy intake seemed to be consistently lower in the women probiotic group when compared with women in the placebo group⁽³⁸⁾. In contrast with current results, the findings of a study carried out in Japan, there was no significant difference in the intake of energy or main nutrients in the groups at any of the three different time points (week 4, week 8 and week 12)⁽²⁷⁾. Hence, the observed reductions in body measurements cannot be solely attributable to changes in calorie consumption; instead, they may be attributable to the impact of synbiotics on the GM of individuals, hence inducing alterations in energy metabolism and perhaps facilitating weight reduction irrespective of calorie limitation⁽³⁹⁾.

The mechanisms behind the reduction in anthropometrics and food intake are intertwined. The alteration of host energy homeostasis is one mechanism to reduce weight⁽⁸⁾, which includes the harvesting, storing and expenditure of energy obtained from the diet. For example, a 20 % increase in Firmicutes and a 20 % decrease in Bacteroidetes were associated with an additional energy harvest of 150 kcal/d⁽⁵⁾. Also, SCFA, which are by-products of microbial metabolism, may help regulate host homeostasis in different ways. For example, SCFA affect the production of serotonin (5-HT), which prolongs satiety and reduces food intake⁽⁴⁰⁾. SCFA can also induce satiety in other ways; for example, acetate and propionate stimulate leptin secretion⁽⁴¹⁾; butyrate releases glucagon-like peptide-1⁽⁴²⁾. Additionally, through the postprandial phase, both glucagon-like peptide-1 and peptide YY are also produced in the intestine under the effect of SCFA^(43,44). Also, Backhed and his colleagues said that the change in body composition caused by probiotics could be the result of fasting-induced adipose factor suppression in the gut, which would change the production of SCFA⁽⁴⁵⁾.

Similar to the present study findings, applying a hypoenergetic diet and probiotic cheeses lowered the values of FBG by 18 % in the treatment and control groups; yet only the control group achieved statistical significance⁽²⁶⁾. Administration of a multi-strain probiotic supplement over a period of 6 months also resulted in a significant reduction in circulating FBG (38 %) as compared with the baseline among treatment naïve subjects with T2DM; however, there were no statistically significant differences in FBG between the placebo and probiotic groups at both the 3-month and 6-month time points⁽⁴⁶⁾. In a 3-month intervention using a multi-strain probiotic for athletes, both the treatment group and the control group of female participants saw a drop in their FBG and HbA1c levels. In addition, a beneficial decrease in FBG concentration was observed in the male participants who received the probiotic intervention, whereas there was an increase in the male participants who received the placebo⁽⁴⁷⁾.

In terms of lipid profile, no significant changes between groups were observed in the present study. Other findings confirm that multispecies probiotics have a positive effect on the lipid profile of postmenopausal women with obesity⁽⁴⁸⁾. Another randomised controlled trial, which lasted for 3 weeks, evaluated the effect of a hypoenergetic diet with 50 g/d of full-fat probiotic cheese containing L. plantarum TENSIA on the lipid profiles. The combination of diet and probiotics reduced the values of TC and LDL-cholesterol significantly in the treatment group and control groups, while HDL-cholesterol and TAG were significantly reduced in the treatment group only⁽²⁶⁾. In the same context, a meta-analysis finding found that probiotic yogurt significantly lowers TC and LDL-cholesterol levels in subjects with mild to moderate hypercholesterolaemia, specially, studies lasting more than 4 weeks, but there was no significant effect on HDL-cholesterol or TAG levels⁽¹²⁾. Additionally, Sabico et al. reported the consumption of multi-strain probiotics having significant benefits in terms of reduced TAG (48 %), TC (19 %) and the total/HDL-cholesterol ratio (19 %) in the probiotic group⁽⁴⁶⁾. In contrast, Michael et al. noticed that the TC, HDL-cholesterol and TAG levels remained unchanged through 6 months for the study population; moreover, LDL-cholesterol levels increased 2·7 % from baseline in both the probiotic group (0·087 mmol/l, P = 0·07) and the placebo group (0·088 mmol/l, P = 0·06)⁽²⁵⁾. Similarly, Kadooka et al. also found no significant changes in both lipid metabolism-related parameters, such as TC, LDL-cholesterol and HDL-cholesterol, and physiological parameters, such as blood test, urine test, blood pressure or pulse rate⁽²⁷⁾.

Several hypotheses have been suggested on the mechanisms by which probiotics can reduce cholesterol levels, based mostly on in vitro research, for instance, bile salt hydrolase activity, binding of cholesterol to the probiotic cellular surface and production of SCFA⁽⁴⁹⁾. Bile salt hydrolase, which is expressed in probiotic strains, deconjugates bile salt to become less efficiently reabsorbed than conjugated bile acids, leading to the excretion of significant amounts of free bile acids in human faeces; thus, more cholesterol is needed to replace excreted bile salt, which ultimately reduces TC in the blood⁽⁵⁰⁾.

The study’s limitations include its duration of 12 weeks. Despite observing significant changes within the probiotic group, the absence of clinically significant differences between groups suggests that extending the treatment period might be necessary to achieve noticeable clinical outcomes. Michael et al. (2020) demonstrated that a meaningful impact on individuals with obesity typically requires at least 6 months of supplementation with a multi-strain probiotic⁽²⁵⁾. Nonetheless, this study holds significance as the first of its kind to investigate the anti-obesity effects of multi-strain probiotics in a homogeneous ethnic Arab Saudi adult population. Moreover, it maintains merit due to its implementation of adequate statistical power and rigorous blinding procedures. Furthermore, the intervention protocol allowed for an assessment of probiotics in conjunction with the benefits of a hypoenergetic diet intervention.

In conclusion, a 12-week supplementation of multi-strain probiotics among overweight or obese Saudi adults showed beneficial effects on anthropometric indices, FBG and LDL-cholesterol compared with baseline, with no such improvements observed in the placebo group. However, these changes did not reach clinical significance with the exception of dietary fat intake in favour of the probiotics group. Future research should consider longer trial durations to verify whether alterations in GM composition would lead to clinically meaningful outcomes following extended probiotic intake.

The authors thank B-Crobes Laboratory Sdn. Bhd., Malaysia, for providing the probiotics ‘MCP^® BCMC^® strains’ and placebo sachets to be used in the clinical trial. B-Crobes did not contribute to the study design, data collection, data analysis or interpretation, manuscript writing or the decision to publish the results. The authors are also thankful to the work team from inpatient pharmacy at King Khalid University Hospital: Doaa Abdulaziz Bintaleb, Sondus Issam Ata and Abeer Alshareef for performing subject randomisation and dispensation of the study product.

This work was supported by Researchers Supporting Project number (RSP2024R21), King Saud University, Riyadh, Saudi Arabia.

All authors declare no conflict of interest.

Conceived and designed the experiments and investigation: S.M.A., H.A.F. and N.M.D. Recruited the patients and performed the data collection: S.M.A., T.A.B. and S.A. Performed and validated the sample collection and analysis: S.M.A., S.S.S. and S.D.H. Supervision: H.A.F. and N.M.D. Writing – original draft: S.M.A. Writing – review and editing: H.A.F., N.M.D. and S.S. The published version of the manuscript has been reviewed and approved by all authors.

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of King Saud University College of Medicine, Riyadh, Saudi Arabia (IRB Log No. E-20-5503, 12·07·2021). Written consent was obtained from all subjects involved in the study.

Data that have been collected or analysed for the current study are accessible from the corresponding author upon reasonable request.