This research was funded by China’s Acupuncture Neuroscience and Artificial Intelligence Innovation Research Team and the Traditional Chinese Medicine and Artificial Intelligence Core Faculty Teaching Team, and undertaken by researchers from China’s Meishan City People’s Hospital, Chengdu University of Traditional Chinese Medicine, and Zigong First People’s Hospital.
“This meta-analysis summarised the results of eight RCTs, showing that probiotics, prebiotics, and synbiotics significantly improved Hb levels in patients with anaemia,” wrote researchers in BMC Gastroenterology.
Anaemia is a globally prevalent health issue, with iron deficiency anaemia being the most prevalent. It can lead to health problems, including impaired cognitive and physical development, severe fatigue, and reduced work capacity. Anaemia particularly affects children, women, and the elderly in both developing and developed countries. It is also highly prevalent among men, particularly in the elderly population.
Studies have shown that the incidence of anaemia significantly increases with age, especially among men aged 80 years and older. In individuals aged 65 years and above, the prevalence of anaemia ranges from 11–65%.
Current treatment for anaemia often relies on iron supplements or erythropoiesis-stimulating agents, although these therapies may show limited efficacy for some patients.
Recent evidence suggests that probiotics, prebiotics, and synbiotics, as microbiome modulators, hold significant potential in the treatment of anaemia. These interventions may enhance iron absorption and improve overall blood health through their impact on gut microbiota, thus providing an alternative or complementary approach to conventional treatments.
For example, probiotics may improve gut health by enhancing nutrient absorption, particularly iron and other micronutrients. They may also reduce gut inflammation, creating a more favourable environment for iron uptake.
Prebiotics can increase production of short-chain fatty acids, which enhances iron solubility and absorption in the intestines.
Combining probiotics and prebiotics, synbiotics optimise gut microbiota balance and functionality. This dual action improves iron bioavailability and absorption while reducing factors like inflammation that may inhibit nutrient uptake.
Researchers therefore wanted to explore the viability of these interventions for anaemia treatment.
Exploring the effects of prebiotics, probiotics, and synbiotics on anaemia
Researchers reviewed eight randomised controlled trials (RCTs) with a total of 632 participants. They were mainly diagnosed with iron deficiency anaemia and anaemia from chronic kidney disease.
The treatment groups received probiotics, prebiotics, or synbiotics, while the control groups received placebo, alternative treatments, or no treatment. The primary outcome was Hb levels. Secondary outcomes included serum iron and serum ferritin, both indicators of iron content in the body.
For Hb levels, the overall weighted mean difference was 10.760, indicating a significant improvement among participants who received probiotic, prebiotic, and synbiotic treatment compared to the control group.
Also, the probiotic group had higher serum iron levels compared to the control group, with a significant weighted mean difference of 3.835 between these two groups.
However, there was no significant improvement in serum ferritin levels between the probiotic group and the control group.
These results were reported with a 95% confidence interval, indicating that the observed improvement following treatment compared to the control group is statistically reliable. However, the presence of moderate to high heterogeneity highlights significant variability in the outcomes across the studies.
Given the substantial variability in Hb results across studies, additional analyses were conducted to identify factors contributing to these differences. The subgroup analysis examined disease causes, treatment duration, dosage, and probiotic type.
Factors influencing treatment efficacy
Further analysis revealed that patients with chronic kidney disease-related anaemia showed significantly higher Hb levels after probiotic treatment compared to the control group, with a weighted mean difference of 14.611 between the two groups. Hb levels were also higher in patients with iron deficiency anaemia, with a weighted mean difference of 3.917 between the treatment and control groups.
Treatment duration of eight weeks and 12 weeks similarly yielded significantly higher Hb levels among the treatment group compared to the control group.
Patients receiving larger doses of more than five grams experienced a significant rise in Hb levels, with a weighted means difference of 9.800 between the treatment group and the control group.
Patients receiving lower doses of less than five grams similarly showed significant improvement in Hb levels, with a weighted mean difference of 13.341 between treatment group and control group.
These results suggest that while disease type, treatment duration, and dosage each plays a role, they are not the sole factors influencing treatment efficacy.
Microbiota modulators could be key influencers of efficacy
When researchers compared the results between the probiotics and synbiotics groups, both showed significant improvements in Hb levels, with a weighted mean difference of 7.917 and 9.787 respectively. Notably, the synbiotic group exhibited consistent results with little variability with 0% heterogeneity, indicating reliable efficacy.
As for the prebiotics group, it did not show a meaningful impact on Hb levels. Furthermore, the results displayed extremely high variability with high heterogeneity of 99.3%, suggesting inconsistent effectiveness or a limited role in anaemia treatment.
“Based on the results of the subgroup analyses, we can conclude that the source of overall heterogeneity may stem from the different types of microbiota modulators used,” said researchers.
Probiotics, prebiotics, and synbiotics therefore have potential roles in improving clinical outcomes in patients with anaemia, with a particular focus on their regulatory effects on gastrointestinal factors.
Synbiotics have demonstrated more pronounced efficacy through various mechanisms, which include enhancing gut microbiota balance, reducing levels of pro-inflammatory cytokines, and decreasing the accumulation of uremic toxins.
Current findings also suggest that synbiotics effectively alleviate abdominal discomfort and improve systemic inflammation. These effects may contribute to enhanced intestinal absorption of iron and other nutrients, which could further ameliorate anaemia, said researchers.
This systematic review suggests that probiotics, prebiotics, and synbiotics may improve Hb levels and iron metabolism markers in individuals with anaemia, concluded researchers.
However, due to the limited clinical studies and the small overall sample size of RCTs in this review, further research is needed to clarify whether different strains of probiotics or different prebiotic components, and their combinations in synbiotics, have varying impacts on anaemia improvement.
“Future research should include high-quality randomised controlled trials to explore the specific role of synbiotics in anaemia, particularly their impact on gastrointestinal factors, such as modulating gut microbiota balance and reducing inflammation, and compare their efficacy with probiotics or prebiotics alone.
“This will help optimise clinical intervention strategies and determine the appropriate dosage and combination of these treatments. Moreover, investigating the interaction between these microbiota modulators and traditional anaemia treatments is another important direction for future research,” said researchers.
Source: BMC Gastroenterology
DOI: https://doi.org/10.1186/s12876-024-03562-8
“Efficacy of probiotic, prebiotic, and synbiotics supplements in individuals with anemia: a systematic review and meta-analysis of randomized controlled trials”
Authors: Qian Hu, Ying Liu et al.
