Can Probiotics be an alternate treatment regime for Malaria?
by Timothy Bamgbose
Malaria is a life-threatening disease caused by various strains of malaria parasites, posing a severe threat to human health worldwide. It is estimated that 3.3 billion people are at risk of developing the disease. Probiotics, “live microorganisms which when administered in adequate amounts confer a health benefit on the host”, have shown promise in treating and preventing malaria by enhancing the immune response in the host. Recent research has explored the potential of probiotics in enhancing the immune response and reducing the severity of malaria. This is due to their strain-specific effectiveness against various pathogens and their ability to modulate intestinal microorganisms, thereby influencing immune cells and Peyer's patches cells (Mahajan et al., 2021). Recent research on the human microbiome has revealed a link between resident microbial communities and the risk of blood parasites, offering potential for microbial-based disease treatments such as probiotics. The gut microbiome plays a crucial role in the immune response to malaria, and probiotics can modulate the microbiome by introducing beneficial microorganisms that can enhance the immune response (Rohrer et al., 2023). My research focus is on the potential of probiotics for malaria prevention and treatment (Fig 1) (Bamgbose et al., 2021).
Gut Microbiota produces antimicrobial peptides, metabolite and stimulate humoral immunity that can be a mechanism through which an individual develops resistance to malaria infection. Bamgbose et al., 2021
The immune response plays a crucial role in the pathophysiology of malaria. Chloroquine, once the drug of choice for treating Plasmodium falciparum malaria, has become less effective due to the emergence of resistance among this species. Therefore, alternative treatments that employ probiotics as an adjuvant therapy or delivery vehicle for vaccine are being explored. Recent studies have demonstrated a connection between the host microbiome and susceptibility to malaria, particularly in the mammalian setting (Stough et al., 2016). For instance, genetically similar mice that are resistant to P. yoelii exhibit differential bacterial gene expression compared to susceptible mice (Stough et al., 2016). Additionally, the gut microbiome of mice enriched with Lactobacillus and Bifidobacterium increased resistance to Plasmodium infection. Similarly, a longitudinal study of human stool samples collected during a high Plasmodium falciparum transmission season reveal bacterial community profiles that correlate with malaria infection risk, hence, showing the correlation between gut microbiome and disease onset (Villarino et al., 2016).
Resistance to malaria can be induced in animals that were previously susceptible to malaria through the alteration of the microbiome. This was inferred from the study that reported that injecting mice with Lactobacillus casei can confer resistance to P. chabaudi, resulting in reduced parasite load and shorter infection period (Villarino et al., 2016). Treating susceptible mice with antibiotics followed by yogurt probiotics containing Lactobacillus and Bifidobacterium can also lead to lower parasite infection intensity. While the precise mechanism of resistance in these examples is unclear, increased levels of host immune response are associated with reduced infection severity in mice, indicating an interactive relationship between the microbiome, host immune system, and pathogen infection.
Although most of the microbiome research in the context of Plasmodium infection has been conducted using model organisms such as mice and also experimentally in humans. However, the extent to which microbial communities may impact parasite infection in wild populations and non-mammals remains poorly understood. To investigate the correlation between gut microbiome composition and Plasmodium infection in wild birds, Rohrer et al. (2023) conducted a study using 16S rRNA gene sequencing of faecal and blood samples from wild Eurasian tree sparrows in the United States. The results indicated significant differential abundant bacteria, with the greatest representation within the phyla Proteobacteria and Firmicutes in Plasmodium-infected birds. These differentially abundant taxa may serve as a starting point for experimental investigations aimed at establishing the relationship between microbial abundance in the gut and Plasmodium infection. In addition, recent research by Aželytė et al. (2023) has utilized the computational tool PICRUSt2 to predict functional profiles in bacterial communities in infected and healthy birds. The study found that infection with P. homocircumflexum was linked to the presence of specific degradation and biosynthesis metabolic pathways that were not present in healthy birds. Some of the metabolic pathways that decreased in abundance in the infected group showed a significant increase in the later stages of infection. These results suggest that avian malaria parasites can have a significant impact on the assembly of bacterial communities within the host gut microbiome. Moreover, modulation of the microbiome by malaria parasites could have negative consequences for the health of the host bird. Thus, understanding the intricate interactions between birds, malaria parasites, and the microbiota may prove beneficial in identifying key microbial players and developing interventions aimed at controlling avian malaria at the same time extrapolated to human malaria.
Probiotics can modulate the gut microbiome by introducing beneficial microorganisms that can enhance the immune response and have been shown to stimulate the production of antibodies, such as IgA and IgM, leading to an overall boost in the immune response (Shah et al., 2023). A study conducted by Mahajan et al. (2021) investigated the potential of probiotics in the prevention and treatment of malaria. The study used Lactobacillus acidophilus, Lactobacillus plantarum, and Bifidobacterium bifidum, which are commonly found in fermented foods such as yogurt and kimchi. The probiotics were administered orally to mice infected with Plasmodium berghei, a parasitic strain that infects rodents. The study found that the probiotics significantly reduced the severity of the infection by reducing the presence of parasites in the blood.
Another study conducted by Villarino et al. (2016) investigated the potential of probiotics in the prevention of malaria in mice. The study used a combination of antibiotics followed by yogurt probiotics containing Lactobacillus and Bifidobacterium. The results of the study showed that the probiotics significantly reduced the intensity of the infection. While these studies demonstrate the potential of probiotics in the prevention and treatment of malaria, further research is needed to determine the optimal probiotic strains, dosages, and treatment regimens. In addition, it is important to note that the effectiveness of probiotics may vary depending on the specific strain of the malaria parasite and the individual's microbiome composition.
The potential of probiotics for malaria prevention and treatment is an exciting area of research that warrants further investigation. If successful, probiotics could provide a safe and cost-effective alternative to current malaria treatments that are often associated with side effects and drug resistance. Moreover, probiotics could potentially be used in combination with current treatments to enhance their efficacy.
In conclusion, the use of probiotics in the prevention and treatment of malaria represents a promising avenue for future research. With continued investigation and development, probiotics may prove to be a valuable tool in the fight against this devastating disease.
References
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