By: Kirk Anderson
A probiotic is a living microbe that when consumed, has health benefits. Simple enough. But to truly understand probiotic science and its intimate relationship with consumerism, lets look at human probiotics. Googling with particular attention to the source of scientific information, we find that hopeful advertisement or colorful subjective comparison often qualifies as probiotic “science”. In other words, the profit motive is seemingly more important than scientific information. Who knew? Turns out, the vast majority of products for sale have not been evaluated for effectiveness, and there is no real oversight of the probiotic industry. But this is certain to change in the future as probiotics are genetically altered for drug delivery and other purposes (Hoffmann et al., 2014). Most probiotic brands simply provide their own internal assessment and advertise a long list of unverified benefits. This is not unlawful, just hopeful… like buying snake oil. Perhaps the most damaging misnomer, the word “probiotic” is often swapped out with “microbiome”; the native, co-evolved microbes that are already an integral part of the host ecosystem. Later, I use the word probiotic to identify a purchased product containing live microbes that you then feed to yourself or your livestock. I use the word microbiome to refer to the native microbes that have formed tight partnerships among themselves and within and throughout the host ecosystem. In general, the microbiome get a place (niche) to live in the gut, and the host organism gets a front-line defense of tiny occupants that protect their blood and organs. In fighting to keep their home in the gut, the microbiome members cooperate with one another and simultaneously protect the host.
Figure 1. Results sequencing the gut microbiome following long-term probiotic application (Anderson et al., 2024). Microbiome structure and membership was unaffected following many months of probiotic treatment. Each dot represents the microbiome of a single honey bee gut. When differences are significant, the dots of a particular treatment cluster independently of the control. Probiotics A and B contain the same non-native bacterial species.
Increased consumer awareness of the gut microbiome, vital for overall health, has recently inflated the human probiotic market to over $100 billion annual worldwide! I think I know why, and it’s certainly NOT because controlled scientific studies have demonstrated the health benefits of consuming probiotics. It is simply because consumers became vividly aware that the native gut microbiome affects a great variety of host health metrics. This scientific consensus (plus a little hope and fear) blew the roof off the probiotic market. Considered “pro-life”, the microbiome is often and erroneously labelled “probiotic” via advertisement. Welcomed by the probiotic industry, this semantic difference has developed into a widespread and highly effective strategy of “bait and switch”. The variety of products now labeled “probiotic” has become overwhelming, a prophecy advanced in Idiocracy, a 2006 film depicting a dystopian future wherein electrolytes (like those in Gatorade) are a universal tonic.
From whence sprang this dystopian future? First came the cultural understanding that microbial fermentation of food is safe. This observation accords well with a criteria long applied by the FDA, called GRAS (generally regarded as safe), meaning that long-term historical consumption of such microbes and their fermentation products has not damaged human health. However, the FDA stops at safe, and provides no judgement or oversight of potential benefits (Hoffmann et al., 2014). As a cultural result, non-pathogenic (GRAS) bacteria like Lactobacillus and Bifidobacterium are widely considered synonymous with safe consumption, and this association helped unify a great variety of life forms under a single umbrella of health. But nature is never that simple; there exist thousands of known species and strains of these bacteria, and each one has developed (evolved) according to a particular host gut or environmental condition wherein it finds reproductive success (fitness). This success is highly dependent on its native environment, which includes not only the host species, but many other microbes with which it has established long-term contracts. This dependency within and between microbial species and their native environment is why the transplantation of microbes into a novel environment (ecosystem) is simply ineffective. It is similar to tossing horses into the ocean to pull your boat. Or in the case of non-native honey bee probiotics, tossing a rabbit into the mouth of a combine. In humans, the gastric acid in the stomach kills most bacterial strains before they can move into the intestine where they might have their benefits. When and if they get to the large intestine, they are faced with an established microbiome that has little tolerance for non-natives. Similar reasons explain the non-utility of popular honey bee probiotics, the colony environment is highly acidic, water deficient and replete with antimicrobial attributes. True to its namesake, the honey bee colony and its associated gut environment is highly inhospitable to non-native microbes.
To provide a human example, many are told by their physician to consume some type of probiotic following antibiotic treatment. I certainly haven’t read all the papers on this subject, so I will report a recent meta-analysis, a type of study that distills information from many separate studies and mountains of data. This particular meta-analysis details the quality and impact of human probiotic application following antibiotic treatment (Elias et al., 2023). The goal of this meta-analysis was to synthesize the iron-clad scientific evidence for probiotic assisted recovery. All of the included studies were randomized controlled trials selected according to their rigorous methodology. Of 11,769 studies retrieved from three databases, only 20 trials qualified for further analysis based on the selected attributes. Across all studies, there were no significant differences in gut microbiome diversity between the “probiotic supplemented” and the “antibiotics alone” groups following antibiotic therapy. In short, the study found no real indication that probiotics had any effect on antibiotic recovery.
Not to be labeled a complete nay-sayer, I must confess there is a small scattering of scientific evidence that probiotics can provide benefits in humans, in particular gastrointestinal disease, including irritable bowel syndrome, C. difficile infection and small bowel overgrowth. One big success story involves the transmission of microbes from their native environment in one healthy individual back into their native environment in a separate diseased individual of the same species. In general though, most probiotics presently on the market do not follow this rule, and are largely ineffective as a result. Even when probiotics work, the benefits are sporadic and seem to rely on the individual, like certain medicines. As a species, humans differ from the honey bee for a variety of microbiome characteristics. Humans have highly unpredictable microbiomes with thousands of known species, many still uncharacterized. It is hard to find two human microbiomes that are similar. This interpersonal variation in microbiome content among humans makes it difficult to even define a ‘healthy’ vs. ‘dysbiotic’ microbiota.
On the other hand, the worker gut microbiome of the honey bee is simple and rigidly consistent in structure and membership (Moran, 2012). Its like no other microbiome in nature. How did this come to be? It has been proposed that the stability and availability of a deep and omni-present niche (the adult worker gut) has led to the evolution of this very predictable and integrated system. The nature of reproduction in the honey bee (swarming) involves thousands of highly similar sister individuals. The worker bees of the present moment have had continuous and intimate physical contact with their ancestral lineage as it stretches back through the ages. Over evolutionary time scales, the swarm quality and size largely determined the survival of a lineage and its microbiome. At each reproductive event, thousands of worker bees alight, carrying a wide variety of native and highly co-evolved bacterial types within their guts and on their bodies. With few exceptions, each one of these adult worker individuals is carrying an integrated and functional gut microbiome. The depth and continuity of the surviving swarm has thus facilitated intimate co-evolution of the gut microbiome with the host organism. In this way, a deep variety of compatible microbiome signatures are transmitted from swarm to swarm across generations.
The popular probiotic brands fed to honey bee colonies contain non-native bacteria that are facultative anaerobes, meaning that they function in the presence and absence of oxygen. Thus, these introduced probiotic species would need to survive the highly oxygenated and water deficient colony/hive environment, and then establish in the anaerobic hindgut of workers. But examining the genomes and growth requirements of each species in this probiotic cocktail reveals that none of the introduced species are equipped to survive the colony/hive environment, much less the worker gut. They are the same species/strains used in a variety of probiotic products, selected perhaps because the companies acquired the legal right to use them. They are bacteria that evolved in the gut of a human infant, soil, ground dwelling bird plumage, mammalian gut, oxygen poor plant matter or the like. None of them evolved with the honey bee or pollination environment. Many of these bacterial species are the self-same species fed to chickens, cows, goats, horses and swine under different labels. Why would any reasonable person expect these bacteria to survive across such a variety of host species much less in a honey-rich environment?
Science recently answered this question with next generation sequencing, a highly sensitive process that reveals all the bacterial types in the colony whether introduced or native. Two independent labs report the same finding; non-native microbes are quickly and completely annihilated by the colony environment (Anderson et al., 2024; Damico et al., 2023). In each study, probiotics were applied as directed, 10 grams per feeding with the probiotic species introduced to each colony at a stated concentration of five billion bacterial cells. Examining over seven million DNA signatures from worker guts, the Damico et al. (2023) study never even detected the probiotic sequences in the guts, even during active treatment with the probiotic powder. I praise these authors for their decision to sequence the microbial DNA signatures found within the probiotic powder. This allowed them to compare directly the sequences from the probiotic powder to the sequences in the guts of worker bees. Despite sampling workers immediately following the application of probiotics, they did not find one single match between the introduced probiotic species and the microbes present in worker guts. A separate study showed nearly the same result; Only twenty-three of 14 million DNA signatures may have originated with probiotic application (Anderson et al., 2024). These two independent studies provide overwhelming evidence that non-native probiotics simply do not survive in the honey bee colony or gut. I apologize to those with vivid imaginations, but the rabbit did not fare well in the mouth of the combine.
Maybe one day a probiotic will work in honey bees… but first we might ask: Is this even necessary? For some indication, we examine a decade old probiotic story that begins in the honey bee crop. Eager to enter the probiotic markets, the entrepreneurs championed by this story quickly patented the use of their bacterial strains. It was their immediate goal to market a probiotic, whether it was fed to honey bees, humans or whatever. Early on, they marketed their probiotic as a human hangover cure among other creative ideas. They also performed impactful honey bee science in support of this business direction, and have reaped a tidy profit from their endeavors. To fully grasp this story, we have to defy our previous distinction of probiotic vs. microbiome. This proprietary probiotic contained thirteen bacterial species native to the honey bee microbiome. These nine Lactobacillus and four Bifidobacterium species are referred to as LAB-H13, hbs-LAB, symBEEotic, or SupernormalTM depending on the target audience. These 13 species were isolated from the worker crop, but actually find their reproductive niche in the worker hindgut (Corby Harris et al., 2013). While all of these native microbiome species inhibit the growth of AFB in a petri dish, colony level application of this native probiotic had no effect on AFB disease symptoms (Stephan et al., 2019). This result may reflect the omnipresence of the native microbiome in the colony, indicating no need to reintroduce the native microbiome to the colony as a probiotic. However, these researchers did discover that it was safe for humans to snort the 13 native honey bee bacteria. But again, they found no effect of their 13 bacteria on the human nasal pharyngeal microbiome or the associated disease state. Maybe there’s a lack of pollen or honey in that booger factory.
I must admit that I dabbled with the idea of probiotics many years back, testing two very different hive bacteria. We selected these candidates for their ability to clear the first hurdle as they are functionally adapted to the hive environment. However, we found no evidence that supplying colonies with an excess of these hive (social) microbes improved individual worker health or colony growth, so we threw in the towel. Like the earlier example, these native bacteria are already prevalent within the colony, such that introducing an excess of the same native microbes may be overkill. Both of these hive bacteria were later revealed as species transmitted with the swarm, species that consistently populate the queen and larval gut. With this new information, I thought it best to investigate the nature of these species in the colony system so I abandoned the probiotic angle. Of course, my intellectual property belongs to the U.S. government, so I cannot reap the profits from any scientific endeavor, as would an entrepreneur.
In conclusion, despite all the advertising claims, science reveals that most probiotics are simply not effective. Nevertheless, the human probiotic market has flourished according to an age-old strategy of hope and fear. The same tactics appear to work for honey bee probiotics. By definition, the hopeful cannot include the scientist. If a “scientist” desires or fears some result or the material profits of some idea, their impartiality has fallen into bondage, and they are a scientist no longer. They have become an entrepreneur, grasping hopefully for a piece of that $100 billion annual revenue. Consider the source.
