by Emerging metagenomic research increasingly shows the clinical importance of maintaining a healthy gut microbiome. However, this can be challenging for patients who are managing chronic vector-borne infections with long-term antibiotic regimens. Physicians will often recommend probiotics that may help alleviate unwanted side effects, but what are they? And how do they work?
Probiotics are described as “good microorganisms” that confer a benefit to the host after the appropriate amount is ingested. They are typically acquired via a supplemental pill found in a pharmacy, or even from foods that contain live cultures. The efficacy of these delivery systems vary greatly, but high potency, live probiotics have been shown to outperform freeze-dried or food-based products. The most common microbes that are used are bacteria, like Lactobacillus or Bifidobacterium species, and certain strains of Saccharomyces (yeast).
Researchers believe there are a couple of key mechanisms that probiotic products engage with:
1. Balancing of Intestinal Microflora
The millions of microbes that colonize our intestinal tract play important roles in nutrient metabolism, pH maintenance, and more. For example, short chain fatty acids (SCFA) that are used in energy production and cellular signal pathways are produced when the beneficial microbes break down the fiber in our diet. When a pathogen or something else changes the optimal population of microbes, these processes are hindered. Research suggests that probiotics help restore the gut microbiome to a healthy state following antibiotic therapy. In one study, Lactobacillus casei was found to stimulate intestinal enzyme activity that led to a decreased presence of pathogenic bacteria.
2. Mediation of Immune Response
Research on how probiotics affect the gut microbiome and the resulting host immune response is still in the early stages. However, findings suggest that intestinal microorganisms can play a protective role in the immune system. This makes sense from an evolutionary perspective. Like parasites, these microbes that have evolved with us over time could be mediating our immune response through changes in gene expression and complex signaling pathways that involve intestinal epithelial cells. A recent review article describes the roles of probiotic microorganisms in modulating the release of proinflammatory cytokines. In-vitro studies suggest that when there is a larger presence of “good bacteria”, fewer inflammatory markers are present.
Why is this important for flea-and tick-borne diseases?
Chronic flea- and tick-borne bacterial infections are often treated using single or combinations of broad-spectrum antibiotics. These medications effectively destroy target pathogens, but they also eliminate beneficial bacteria inhabiting the gut at the same time. When this takes place over a long period of time, it can be difficult for the microbial populations to repopulate and stabilize without intervention. Probiotics can serve as the intervention needed for patients experiencing unwanted treatment effects such as antibiotic-associated gastrointestinal distress. There is conflicting evidence from studies over the past 10 years, but the consensus seems to be that Lactobacillus, Bifidobacterium, and Saccharomyces species may be especially helpful for patients in the recovery phase following antibiotic therapy. Experts recommend using probiotic preparations where efficacy is supported with good published data.
Furthermore, a significant aspect of understanding why symptoms of flea- and tick-borne diseases vary greatly between patients is the host immune response. Bartonellosis has been shown to cause immunological dysfunction in case studies, and Lyme borreliosis can lead to persistent immune system effects even after treatment. If human clinical studies can show that probiotics positively influence the immune system via gut microbe-immune interactions, probiotic supplementation may be a way of treating some of the immune issues associated with chronic flea- and tick-borne illness.
How are these products regulated in the United States?
In the US, probiotics are generally sold as food supplements and thus are regulated by the US Food and Drug Administration (FDA) Center for Food Safety and Applied Nutrition. Products made from foods labeled “generally regarded as safe” (GRAS) by the FDA and following current good manufacturing processes (cGMP) can be sold after pre-market notification.
One limitation to this regulatory pathway, however, is that these probiotics have not been evaluated by the FDA for efficacy and cannot make specific medical claims. This regulatory process allows patients to have greater access to a variety of products but makes it difficult for clinicians to understand exactly how and if probiotics are therapeutic across different patient populations.
The FDA has taken steps to develop a process by which probiotics may be developed as pharmaceuticals. In 2016, the agency released a guidance document on early clinical trials. It has also developed technology to test probiotics for contaminants.
Safety developments are important. For example, in a fecal transplant, instead of growing one or limited species as is done with a probiotic, an entire intestinal microbiome is transplanted. In early 2019, several patients became sick and one died after receiving experimental fecal transplant material that contained antibiotic-resistant E. coli. Following this event, the FDA added more safety requirements for fecal transplants.
Although fecal transplants are far more complex than current probiotic treatments, these regulations move the development of safety standards and processes forward. And research is moving forward in a big way – Cancer Research UK just put $25 million into microbiome research, increasing funding on just three projects specific to cancer to $75 million. As projects like these increase understanding about how microbes work together, future complex treatments can be imagined, and safety regulations are rushing to keep up.
Conclusion
Probiotics are often a go-to supplement for patients on long-term antibiotics. They are well known for relieving antibiotic-associated gastrointestinal distress, but recent studies indicate they could have additional immune-modulating effects. Additional research is needed to fully understand how probiotics influence the immune system and what this means for patients managing chronic infections. Current products on the market include one or limited species, but future products may be more complex as more is understood about how these microbes work together.
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