A serious threat from indiscriminate use of antibiotics: antimicrobial resistance that makes antibiotics ineffective in treating human diseases. This is a problem that extends beyond the simple inconvenience of having ineffective drugs on our shelves. It is a problem that ripples through the population creating impacts at the societal and economic levels, and possibly, even at the historical level.

Let’s break this down. Bacteria are evolving. Heavy antibiotic use is already resulting in a serious public health crisis. And even if we manage to reduce indiscriminate use of antibiotics to treat disease, we are still left with the problem of antibiotics used in animal raising. If your source of income is farming, and if antibiotics increase your farm’s income, then you have a dilemma indeed. Income? Or antibiotic resistance?

It has been suggested that lactic acid bacteria in probiotics such as Yakult and fermented foods can help address the problem. Probiotics can produce antimicrobial bacteriocins. In fact, bacteriocins are produced industrially as food preservatives. And they can be engineered to improve their antibiotic properties.

Drink these bacteria. Get free doses of bacteriocin. Control your bad bacteria.

But not so fast. Although most are generally regarded as safe, we can’t assume all of them are safe. Especially new ones. Normally, new products go through FDA, but it has been pointed out that our current guidelines do not fully appreciate the potential dangers of probiotics.

There are 3 THEORETICAL concerns regarding the safety of probiotics: (1) the occurrence of disease, such as bacteremia or endocarditis; (2) toxic or metabolic effects on the gastrointestinal tract; and (3) the transfer of antibiotic resistance in the gastrointestinal flora. A full assessment of the risks will include 1) antibiotic resistance of the lactic acid bacteria themselves, especially if such resistance lies on a plasmid that can be transferred to an opportunistic pathogen; 2) good manufacturing processes; 3) assessment of virulence genes based on genome analysis. All this, apart from testing and evaluation in animals and humans, particularly in populations that have been shown to be more at risk of adverse events, such as infants, people with gastrointestinal abnormalities, the obese, and the pregnant.

It is this last part which I think is of immediate importance. We have been using probiotics for decades and overall I think they are safe. Neither is there evidence that plasmid sharing to pathogenic microbes is even happening. However, when adverse effects are more commonly seen in subpopulations such as infants then this will show what we already see with drugs and possibly merit a similar pharmacogenetic approach. Then, it may be good to incorporate this knowledge into updated guidelines on the evaluation especially of new probiotics.

I said “may be good”. We still need to consider balance. Lactic acid bacteria are part of our culture, no pun intended. It is too much to ask that the same rigor we apply to new strains or to genetically modified probiotic products be applied to the more familiar bacteria. I think that emerging issues in probiotic safety are best evaluated first in clinical studies. These will produce clinical practice guidelines, to deal with patients case to case. Then, from the epidemiological information that comes with improved monitoring, adjust the FDA guidelines on the basis of whether the cost of gathering data and implementing regulatory rules exceeds the overall health benefits at the population level.

(Q.C. 230915)