Safety of microbial food cultures: an update

Article By François Bourdichon Published November 27, 2023
Article Source: https://www.newfoodmagazine.com/article/196087/safety-of-microbial-food-cultures-an-update/

François Bourdichon examines microbial food culture safety and provides a critical update on fermentation and its potential risks and benefits in food products.

Fermentation is probably one of the oldest food science technologies, used for over 10,000 years by mankind. More recently, however, fermented food products are becoming the new trend in product development, and new combinations are proposed for introduction in the food chain. Is it something to be assumed safe by design? Most certainly not. Microbial food cultures are considered to be safe based on their traditional historical use, but they are not safe per se. They are safe if used properly in traditional food matrices, but crossover fermentation, as suggested by a team at Wageningen University,1 is not safe by design.

Lactic acid bacteria are beneficial on dairy matrices, but some are considered spoilers on meat products. Caution and proper risk assessment prior to usage is therefore mandatory, as failure to do so can have severe if not fatal outcomes, as seen most recently in the US with the fatal sepsis of a neonate following probiotic strain ingestion.2 There were warning signals, but unfortunately they were not heeded.3

The history of safe use

Legal requirements for safety demonstration of microbial food cultures can be found both in Europe and in North America, which tackle the evaluation of novel foods products. These are the European Novel Food Regulation (Regulation (EC) No 258/97 of the European Parliament and of the Council of 27 January 1997 concerning novel foods and novel food ingredients) and the US Food and Drug Administration (FDA) Generally Recognized as Safe (GRAS) regulation. When it comes to novel food process evaluation, Europe considers 1997 as a milestone, while the US-FDA defers to 1958. And science? Considering the historical use of fermentation, it can be complicated, and use of the word ‘origin’ of a microorganism, rather than its ‘isolation’ does not help. Recently, the phrasing has been adapted, but education is still needed.

One definition of ‘history of safe use’ proposes ‘‘significant human consumption of food over several generations and in a large, genetically diverse population for which there exists adequate toxicological and allergenicity data to provide reasonable certainty that no harm will result from consumption of the food’’.4

A history of apparent safe use is not limited to use over a long period; it also includes factors such as the level of exposure to a microorganism. A history of apparent safe use does not, in itself, constitute a risk assessment. Furthermore, no assurances can be made that something is absolutely safe. An appropriate history of safe use does, however, provide evidence in support of a “reasonable certainty of no harm”.5

The history of use, in summary, replaces the exposure assessment part of the risk assessment framework proposed in the risk analysis guidelines of the Food and Agriculture Organization of the United Nations (FAO); it is therefore necessary but far from sufficient to consider that any isolate of the evaluated microorganism’s species is safe.

Safety considerations

According to the FAO/World Health Organization (WHO) expert panel in the 2002 report,6 probiotics have been proposed to be theoretically responsible for four types of side effects: 1. Systemic infections 2. Deleterious metabolic activities 3. Excessive immune stimulation in susceptible individuals 4. Gene transfer.

The gaps in conclusions between clinical microbiologists and food microbiologists is particularly pertinent when it comes to the assessment of lactic acid bacteria (LAB). None of the commonly used food cultures, even when causing relative harm, falls into the category of the 1890 Koch’s postulate, or even the recently proposed molecular ones. As originally stated, the four criteria are:

1. The microorganism must be found in diseased but not healthy individuals 2. The microorganism must be cultured from the diseased individual 3. Inoculation of a healthy individual with the cultured microorganism must recapitulate the disease 4. The microorganism must be re-isolated from the inoculated, diseased individual and matched to the original microorganism.

As for lactic acid bacteria, the postulates one, three and four do not apply: through fermented food products, one can reasonably consider that the global world population is exposed, hence as previously mentioned the lack of exposure assessment relevance and the alternative consideration of history of safe use.

Nevertheless, LAB are sometimes classified as pathogens of concern and infectious substances by clinical microbiologists. Correlation is not causation, and isolation of a microorganism where the medical dogma expects microbial sterility can lead to quite concerning conclusions. When considering the prevalence of opportunistic infections to LAB, one can start by considering the available evidence in scientific literature.7

Opportunistic infections

Commensal bacteria have been described to cause infections in patients with underlying disease. Owing to its natural presence in different sites of the human body and in fermented food products, the genus Lactobacillus has gained particular attention. Lactobacillus infections occur at a very low rate in the generally healthy population – estimated at 0.5 / 1 million per year.

As stated in two reviews of Lactobacillus infections: “Underlying disease or immunosuppression are common features in these cases, whereas infection in previously healthy humans is extremely rare”,8 and “Lactobacillus bacteraemia is rarely fatal per se but serves as an important marker of serious underlying disease.”9 Sporadic infections have been reported in immuno-compromised patients. The underlying problems have mainly been due to the presence of a central venous catheter (CVC), metabolic disorders, organ failure, or invasive procedures such as dental work. Infections by other bacterial species used as food cultures are also extremely rare. In the 2018 re-evaluation, EFSA concluded:10 “The safety concerns described are all considered linked to severe underlying health conditions and therefore do not change the consideration of Lactobacillus spp. for the QPS status”.

Toxic metabolites and virulence factors

Biogenic amine formation in fermented foods by LAB is known in certain cheese types, such as L. buchneri in Swiss type cheese. Following food poisoning outbreaks, metabolic pathways have been elucidated and screening procedures proposed to limit the level of production, by screening for decarboxylase genes or metabolism of histidine and tyrosine. The presence of mycotoxin also raises safety concerns, although the level of expression within fermented food is very unlikely to present a health hazard. Within fungi, the potential for antibiotic production is also an undesirable possibility.

Antibiotic resistance

The antibiotic resistance of food cultures is a point specifically addressed in the Guidelines of the EFSA’s Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) in the first guidelines of 2005, 2008 and most recently the 2018 guidance on the characterisation of microorganisms used as feed additives or as production organisms.11

The role of microorganisms in the spread of antibiotic resistance has been assessed in fermented foods. Results of such studies confirm the role of a reservoir of antibiotic resistance genes from the food microbiota, without identifying any major health concerns to date.

It is considered that strains carrying acquired antibiotic resistance genes might act as a reservoir of transmissible antimicrobial resistance determinants. Gene transfer of antibiotic resistance between microorganisms in the food and feed chain is thus considered to be a topic of surveillance for the safety demonstration of microorganisms.

Every coin has two sides

If it looks too simple, it might not be that simple. Taking for granted that fermentation is by design a safe process is a dangerous path. Traditional use of fermented food products is based on a forgotten series of trial and errors. While this field is blooming and offers tremendous opportunities and positive outcomes, it should not be forgotten that every coin has two faces.

A risk-benefit assessment is needed to make sure that the prize is worth the risks taken. And no matter what the outcome, it should always be restricted by the acceptable level of risk, and in the case of the unfortunate recent event on probiotic-related sepsis, with carefully considered information to the end-user and clinicians.12-13

References

1. Dank, Alexander & van Mastrigt, Oscar & Yang, Zhaoying & Dinesh, Varun & Lillevang, Søren & Weij, Christian & Smid, Eddy. (2021). The cross-over fermentation concept and its application in a novel food product: The dairy miso case study. LWT. 142. 111041. 10.1016/j.lwt.2021.111041.

2. WARNING REGARDING USE OF PROBIOTICS IN PRETERM INFANTS Subject: Risk of Invasive Disease in Preterm Infants Given Probiotics Formulated to Contain Live Bacteria or Yeast [Internet]. 2023. Available from: https://www.fda.gov/media/172606/download?attachment

3. Esaiassen E, Cavanagh P, Hjerde E, Simonsen GS, Støen R, Klingenberg C. Bifidobacterium longumSubspeciesinfantisBacteremia in 3 Extremely Preterm Infants Receiving Probiotics. Emerging Infectious Diseases. 2016 Sep;22(9):1664–6.

4. Bourdichon F, Casaregola S, Farrokh C, Frisvad JC, Gerds ML, Hammes WP, et al. Food fermentations: Microorganisms with technological beneficial use. International Journal of Food Microbiology. 2012 Mar;154(3):87–97.

5. IBID

6. Probiotics in food Health and nutritional properties and guidelines for evaluation [Internet]. Available from: https://www.fao.org/3/a0512e/a0512e.pdf