Probiotics consumption: a “gutsy” move?

Introducing the gut flora 

Here is something that may shock you. The human is technically composed of more microorganisms than cells, in which these microbes essentially outnumber human cells via a ten-to-one ratio. Trillions of these bacterial species are observed to be residing in the intestinal tract (also known to be our gut). This aggregation of microorganisms within the gut is therefore known as the “gut microbiota” or “gut flora”. Going into more specific details, the majority of the gut microbiome are found to be colonising the large intestine (as known as the colon), which is the final part of the digestive tract. 

This surprising yet fascinating nature of the gut microbiota that brings forward a concept the certain variants of bacterial species are actually beneficial towards a person’s health. Theoretically, the metabolic activity within the gut flora could be resembling that of a normal organ. Its role is not only limited to the production of essential vitamins like specific types of vitamin B and vitamin K, but it also has the ability to convert ingested fibres into compounds called short-chain fatty acids (SCFAs) such as acetate, butyrate, and propionate, and they are critical for several reasons. Firstly, they serve as vital energy sources for the cells that are lining the colon, thereby strengthening them. Meanwhile, these SCFAs can also induce the immune response to prevent the invasion of foreign and potentially harmful microbes into our body. 

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Besides that, it was also shown that the gastrointestinal tract shares a physical and chemical communication channel with the brain, which essentially means that any alterations in the gut microbiome would trigger a chain of effects on the brain activity. Examples of such mediums of communication established between these two areas include the production of hormones (meaning that they are chemical messengers) along with small molecules by the gut flora, which are suitable for transportation into the brain and to the central nervous system (CNS). In addition, the microorganisms that colonise the gut may also change the degree of inflammation within the colon, resulting in the regulation of activities occurring in the brain. 

It is important to maintain a stable gut flora, and this is largely dependent on a person’s diet, whereby alterations in the food consumed by an individual may lead to fluctuations in the processes that take place in the intestine. Various studies on the gut microbiota have indicated a connection between gut dysbiosis (meaning that there is an imbalance in the gut microbiome) and the production of various types of diseases within a patient. Common gut-related diseases include type-2 diabetes, heart disease, obesity, colorectal cancer, metabolic syndrome, Alzheimer's disease and depression.

Consequently, this brings about an insightful discussion on probiotics, which are bacterial species with evidence of being able to promote a balance in the gut microbiota. And as a result of that, these probiotics could promote the optimal functioning of the gastrointestinal tract. 

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A brief introduction to probiotics

The Food and Agriculture Organisation of the United Nations and the WHO (FAO/WHO) originally defined probiotics to be “live microorganisms which when administered in adequate amounts confer a health benefit on the host”. This definition was eventually replaced with a more grammatically correct version, which was “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. The new definition garnered wide support to be used as a universal definition, and this considers a wide variety of microorganisms and its applications for health care purposes. Moreover, the definition helps to distinguish between the artificially administered live microbes from the microbial population that were originally colonising the intestines.

The term “probiotics” came from the Latin terminologies “pro” (meaning to cultivate) in combination with “biotic” (meaning life). As a result, probiotics essentially means microorganisms that could promote life. 

It is vital for one to not confuse probiotics with prebiotics. Prebiotics are essentially dietary fibres extracted from food supplements which could not be digested by the body, and these eventually serve as a source of food for the colonic bacteria, and in turn, help to cultivate the activity and growth of the gut microbiota. 

The discovery of the use of probiotics 

A researcher called Henri Tissier first observed the presence of a specific bacterial species known as bifidobacteria that were present in the gut microbiota of healthy babies who were breast-fed by their mothers back in 1899. On the other hand, a group of healthy infants who were fed with formula milk did not possess these bacteria, and they ended up suffering from diarrhoea. This study thus presents an idea that the gut microbiome is a crucial component in the maintenance of a person’s overall health. 

Bringing time forward to the early twentieth century, a biologist from Russia known as Élie Metchnikoff pioneered the discovery of the medical applications of probiotics. He was a strong believer that these “good bacteria”, including the lactic acid-producing microorganisms, are essential for promoting one’s youthful looks and prolonging life. Although his ideas received negative reception from the research community as it promotes the daily consumption of sour milk for an improved overall health, it has been well-acknowledged that Yakult is the world’s first probiotic drink introduced into the market. This was commercialised in 1935 and has been a widely popular choice of beverage. In fact, the Yakult drink is still widely available for purchase in most supermarkets up until today. 

The benefits of taking probiotic products

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The three most common types of probiotic species found in commercial products are bifidobacteria, lactobacillus, and enterococci. It is also important to take note that each of these species are made of various types of strains. There have been reputable documentations of the safety of all three species, and they are recognised as innocuous substances (meaning that they are harmless) in infants.

Overall, consuming probiotics have been linked to the strengthening of a person’s gastrointestinal health, immune system function, stool consistency, and bowel movement. Other than that, female adults are postulated to have an improvement in the health of their reproductive organs as probiotics promote an increase in the concentration of vaginal lactobacilli. 

There are several dozens of probiotic species that exist in the present-day, and many of them present interesting benefits to our health. Although it is important to understand that different variants of probiotic bacterial species manipulate different types of health conditions and diseases. Henceforth, it is important to choose the appropriate type(s) of probiotic supplement for consumption. There are a number of probiotic supplements known as multi-probiotics or broad-spectrum probiotics, which involves the development of a single product combining a variety of species to address a wider range of various health issues. 

Nevertheless, a mixture of public feedback on these probiotic products have been recorded, whereby a significant proportion of the consumer population noted symptoms representing digestive issues (like bloating and gas) when they first take these products. Even though these symptoms were deemed to be common and were expected to go away within the following days, the World Gastroenterology Organisation (WGO) highlighted the potential dangers of probiotic consumption by patients who are challenged with a compromised immune system. So, these immunocompromised individuals are often advised against taking probiotic products unless there was clear evidence of the product’s high safety and efficacy levels in improving their health and well-being. 

Present-day research efforts on probiotics and interesting findings

A large number of current research funding have been devoted towards the study of probiotics, but these studies have only covered the superficial aspects of an in-depth topic. This highlights the vast amount of knowledge that is left unexplored. In particular, the type of probiotic species that are considered to be beneficial for the treatment of numerous health conditions has yet to be classified. 

A variety of mechanisms of action were adopted by probiotics as part of their exerting their function within the gut microbiota, however, the complex details of these mechanisms have not yet been fully elucidated by researchers. Besides that, there were various investigations that generated practical implications for the consumers to bear in mind. For instance, Tompkin et. al. (2011) suggested that taking a probiotic pill 30 minutes before or in the middle of a meal (but not after) is the most ideal timing if one hopes to maximise the health benefits offered by the probiotic supplements. Despite that, although this field of study proposed a higher likelihood of microbial survival if the probiotic supplements were consumed before having a meal, the consistency of intake is found to be more important than timing. To dive into greater detail, the day-to-day recommended dosage usually ranges from a billion to ten billion colony-forming units (CFUs) of bacteria. CFUs is defined as the regular unit used by microbiologists to estimate the population of viable bacteria within a specified sample size. A review paper by Khalesi et. al. (2019) highlighted the temporary enhancement in the supplement-specific bacterial concentration amongst healthy adult subjects when they take probiotic supplements. However, the review could not support the long-term improvement of the gut flora condition, as well as the patient’s general lipid profile upon consumption of probiotics. Hence, a consistent intake of probiotic supplements is shown to be obligatory. 

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An enormous variety of research has been completed to observe if probiotics could be used as a treatment possibility for various illnesses. To start with, many reliable experiments showed a link between probiotic intake and a reduction in the symptoms of irritable bowel syndrome (IBS) within a patient. A study directed by Ford et. al. (2014) demonstrated the effectiveness of probiotics to treat IBS, even though they were still incapable of isolating the precise kind of probiotic species and strain that is essential for the treatment of IBS. 

In the meantime, inflammatory bowel disease (IBD) is a heritable health disorder caused by gut dysbiosis. This normally involves an untimely response by the immune system against the intestinal bacteria. In this scenario, Ghouri et. al. (2014) described the existence of current evidence indicating that prebiotics, synbiotics (meaning products that mixes probiotics and prebiotics), and probiotics might have possible applications as a standardised procedure of treatment for IBD. In general, patients have been shown to tolerate well with probiotics consumption, with only some of them suffering from mild side effects

Furthermore, there were suggestions that probiotics can decrease the probability of patients getting diarrhoea during their antibiotic prescription course. This medical state is professionally labelled as antibiotic-associated diarrhoea (AAD), in which ingesting antibiotics are notorious for disturbing the microbiome that lines the gastrointestinal tract. These bacteria were implied to help prevent the development of an organism called C. difficile in the gut microbiome. This is because C. difficile is known to be a causative agent for AAD. This finding has enormously significant implications, specifically in upcoming probiotic development for toddlers, which are the group of people who are most commonly prescribed with antibiotics. Alongside that, meta-analyses conducted by Hempel et. al. (2012) and Johnston et. al. (2015) highlighted the potential efficiency of probiotics in defending patients from AAD. Still, more research is needed to determine which type of probiotic actually contributes to the increased efficacy of treatment in addition to identifying the appropriate species and strains to be given to patients receiving a unique set of antibiotics for treatment. 

Most probiotic studies on mental health have been fixated on Lactobacillus and Bifidobacterium strains, particularly the L. helveticus and B. longum strains. Interestingly, quite a few experts have even characterised these strains as “psychobiotics”, which is common terminology describing a developing probiotic species that may display some significance to psychiatry, owing to their stimulating possibility for usage in mental health treatments. 

Together with that, another thought-provoking detail about our gastrointestinal tract is that this section of our body houses a “second brain” called the enteric nervous system (ENS). The ENS primarily serves as the nervous system of our gut. It is built with a two-way communication structure with the central nervous system (CNS). This set-up is also recognised as the brain-gut connection, and these two systems function together to bring about an appropriate response by the digestive system to the physical demands set by the resident system alongside the signals from the whole body. Variations in the role of the ENS may result in changes of a person’s mood, and this is a common symptom experienced by numerous patients challenged with either irritable bowel syndrome (IBS) or functional bowel issues such as pain, diarrhoea, an upset stomach, or constipation. 

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Hence, there have been many investigations that suggest a theoretical relationship between the instabilities in the microbiome and the psychological (mental) wellbeing of an individual. An experiment led by Tillisch et. al. (2013) on a group of adult females drinking fermented milk product with probiotics (FMPP) over a month showed significant alterations in regions of the brain that are in charge of a person’s ability to process emotions and sensations. Though, these experimental outcomes were inadequate to be considered as a reliable endorsement for clinical applications. Therefore, this research ought to be recognised as a “hypothesis-generating study” instead of a “practice-changing study” at this moment of time. This could likewise be a catalyst for forthcoming scientific experiments, in which researchers should directly compare the efficacy of the FMPP with a placebo. Furthermore, Steenbergen et. al. (2015) hypothesised that the ingestion of probiotics could possibly be useful in permitting patients suffering from negative thoughts to have an improvement in their mood, which in turn presents another probable preventative therapeutic opportunity aimed at treating depression.  

As well as that, Akbari et. al. (2016) showed some proof that Alzheimer’s disease patients may well benefit from encouraging results of probiotic consumption. In specific, he presented a likely improvement in their cognitive ability, which involves a notable development of their memory and ability to learn by taking a combination of probiotics such as L. acidophilus, L. casei, B. bifidum, and L. fermentum

Other than Alzheimer’s disease, probiotics may also be used to treat depression and anxiety. Messaoudi et. al. (2011) verified that the consumption of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) orally by individuals for one month might assist in the reduction of anxiety levels and remove depression symptoms within patients challenged with clinical depression. 

To shift gears a little, weight loss is an additional popular field explored by academics. As an example, Kadooka et. al. (2013) conducted a multi-centre, double-blind, parallel group randomised controlled trials (RCT), whereby they observed a total of 210 people who had central obesity. Central obesity is largely characterised by the excess amount of belly fat within a person. The research group found out that over a time period of three months, having a consistent day-to-day ingestion habit of the probiotic Lactobacillus gasseri resulted in an 8.5% decrease in stomach fat. However, a steady intake would be essential as subjects who aborted their probiotic diet after the clinical trial recovered their belly fat within one month.

Meanwhile, in the cosmetics industry, Nole et. al. (2014) pointed out a rapid increase in the usage of pre- and probiotics for acne, wound healing, and photoprotection treatment. This was largely due to various reports over the recent years that established the safe use of these organisms for medical applications, but bigger clinical trials would be needed before a credible recommendation could be presented to the public. If the results of these trials show promising implications, researchers ought to focus their next studies on understanding how these prebiotics, as well as probiotics function via their specific action mechanisms in certain skin conditions. This may eventually complement the development of new therapies to treat acne. 

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Atopic dermatitis is, similarly, an alternative aspect for the application of probiotics, whereby it was revealed that exposing a child to these bacterial species during pregnancy or in their early childhood development stages could be critical factors in reducing their risks of developing atopic dermatitis. The age range of 6 months-old to 9 years-old is an important application window, and available probiotic therapies include providing a single or a combination of either Lactobacillus, Bifidobacterium, or Propionibacterium strains. The result of this probiotic consumption has led to a decrease in risk of atopic dermatitis development from 34.7% within the control group to 28.5% amongst the group that took the probiotics supplement. 

On the other hand, DiRienzo (2014) revealed that a probiotic called L. reuteri NCIMB 30242 could be considered as a therapy for high blood cholesterol. Though it was recommended that this organism is further studied in upcoming therapeutic lifestyle change (TLC) dietary experiments prior to introducing them as part of a TLC dietary recommendation. This postulation stems from the ability of L. reuteri NCIMB 30242 to lower the levels of a type of "bad" cholesterol called low-density lipoprotein cholesterol (LDL-C) along with the overall cholesterol concentrations within a patient. 

Moreover, there has been a rising amount of research that validates the consumption of probiotics present in fermented and unfermented dairy products to alleviate symptoms of lactose intolerance. Lactose intolerance is a health condition in which the sufferer cannot break down lactose due to the low activity of an enzyme called lactase within his or her body. 

Oak et. al. (2019) showed the efficacy of using probiotics to treat such disorders using the results from their 15 randomised double-blind studies. This investigation also involves studying eight different probiotic strains that were recognised to possess certain medical benefit(s). Even though the experimental results revealed differences in efficacy levels, an overall positive relationship between probiotic consumption and a decrease in lactose intolerance symptoms were noted. 

Despite existing studies focusing on probiotics for cancer treatment, there has not been any strong evidence to justify its effectiveness. This is largely attributed to the potentially life-threatening side effects that these probiotics might induce, such as sepsis amongst immunocompromised cancer patients. In addition to that, certain types of probiotic supplements may prove to be useful in specific settings, but they may disrupt the metabolism of cancer drugs.

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The current state of the probiotic industry

Currently, an increasing number of people worldwide are challenged with health problems such as obesity, digestion, gastrointestinal infections, or vaginal infection. 

With these increasingly prevalent medical conditions on the rise, many companies are actively attempting to seize the opportunity to do research on the development of viable probiotic products as a treatment for these diseases. The upsurge in health concerns amongst consumers also serves as a trigger for the high growth of the probiotics market in developing economies such as India and China. There are a few companies who have established internal research and development (R&D) centres as part of addressing the industry demands and thus maintain a stable position in such a dynamic market. So, it would not be surprising to soon become a witness of the hugely improved range of probiotic products and their quality in the near future, due to the increased financing of R&D activities. In addition to that, animal probiotics are also gaining recognition globally due to a greater awareness of preventing disease outbreaks and possibly pandemics through ensuring healthy animals. This may be a domino effect that results in a general improvement in global productivity. 

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Nevertheless, the majority of the market interests are situated around the commercialisation of probiotic supplements. Most companies seek to market these products as an excellent health boost and a good treatment option for disease prevention.

With all these aspects taken into consideration, the global probiotics market has been approximated to be worth about US$15 billion per year, and it has an estimated growth rate of around 7%. Thus, this market is frequently labelled as one of the world’s most promising industry verticals. On the other hand, Fortune Business Insights conducted some analysis proposing that the Asia Pacific region is likely to be holding the largest market share. 

Nonetheless, even though there is an increasing number of evidence reinforcing the notion that probiotics are suitable for the treatment of a variety of diseases, there are only a few strains that are available for commercial implications. Moreover, physicians tend to avoid prescribing probiotic products during their standard clinical practices. 

The legislations presented by several governments for probiotic products are also complicated. The United States Food and Drug Administration (FDA), for example, could categorise probiotics as either a food ingredient, a drug, or a dietary supplement. This is often dependent on how it is intended to be used, whereas the European Food Safety Authority (EFSA) has agreed on three core regulatory criteria for investigation prior to making a health claim for probiotic products. These three criteria include product characterisation, the validation of the health benefit presented by the product, and the application of this product towards the general consumer population. 

The market could also be separated into three groups, namely the probiotic food & beverages, probiotic dietary supplements, and animal feed probiotics. Majority of the market growth, however, is largely concentrated within the food & beverage industry, in which there is an increasing number of probiotic products launched within this area of the market.

An overview of probiotic food products

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To dig deeper into the probiotic food & beverages market, probiotics are now available in a variety of forms for consumption like tablets, pills, yoghurts, juices, cereals, and energy bars. Despite all these options, fermented food products have always been the oldest method of consumption, and it is expected to hold the lion’s share of the market. 

Yoghurt is one of the excellent examples of probiotic foods that are offered. This is a type of milk that is produced by fermenting it with friendly bacteria, specifically bifidobacteria and lactic acid bacteria (LAB). Individuals suffering from lactose intolerance are able to eat yoghurt as these probiotics can convert lactose into lactic acid, though it is crucial to note that not every yoghurt product would be containing live bacteria. This is due to the fact that in some yoghurt brands, probiotics would have been killed as part of the processing step. 

On the other hand, kefir is another example of a probiotic food product. It is basically another milk drink that is fermented by bacterial species such as Bifidobacterium bifidum, Lactobacillus acidophilus, and Streptococcus thermophilus (to name a few). It is often viewed as a superior source of probiotics than yoghurt, and it can be eaten by lactose-intolerant individuals. 

In the meantime, sauerkraut is a kind of finely shredded cabbage which is fermented by a probiotic called lactic acid bacteria. It is recognised as one of the oldest traditional European foods and a very popular dish. Along with its probiotic advantages, it is filled with vitamins, minerals and antioxidants. 

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Meanwhile, tempeh is a fermented soybean product that originated from Indonesia, in which a particular type of fungus in the family Mucoraceae known as Rhizopus oligosporus is used as a starter ingredient to make tempeh at home. 

Lastly, kimchi is a spicy fermented side dish first produced in South Korea before it soon became available globally. It comprises a type of lactic acid bacteria called Lactobacillus kimchi and also contains many other variants of lactic acid bacteria that may be of great benefit to the gastrointestinal tract system. 

 Taking all of this into consideration, it is obvious that the ingredients, manufacturing processes, as well as conditions, are key determinants of the product’s characteristics. Thus, changing the manufacturing process is most likely going to result in a product that does not have the exact level of safety and efficacy, unless the original version. Chances of this occurring tend to be pretty high, particularly in situations where food quality controls and regulations have not been tightened and reinforced. 

Companies operating within the probiotics industry

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Numerous players are currently found to be operating within the probiotics market, with excellent examples including (but not limited to) BioGaia AB, Danone, Chr. Hansen Holding A/S, Yakult Honsha Co. Ltd., Probi AB, Lifeway Foods, Inc., Nestle S.A., Ganeden, Inc., E. I. DuPont de Nemours and Company, and Protexin. 

A number of notable features found amongst these corporations include their plans of actions, in which many of them are prioritising the launch of new products. This is a common growth strategy adopted by these players, along with strengthening their channels of distribution for their products. These efforts are often followed by initiatives involving a collaboration and agreement between organisations, expansion, and opportunities for acquisition, with the intention of increasing their customer outreach globally. 

Common customers trends and preferences 

Dr Ben Lebwohl, a gastroenterologist and Director of Clinical Research at Columbia University’s Celiac Disease Centre mentioned that most of the hype around the use of probiotics originated from an increase in customer awareness on the over-prescription of antibiotics, which has led to an increasingly prevalent worldwide issue of antibiotic resistance. In addition to that, widespread knowledge regarding the disruption of the gut microbiota by antibiotics, and how this could eventually affect one’s physical and mental health, has resulted in an increased demand for treatments that don't involve the use of such medication.  

Another important factor that contributes to the high market growth is the growing consumer preference for natural products, especially those that are concentrated on prevention of illnesses. Furthermore, people living in developing economies are beginning to enjoy an increase in their disposable income as well as their living standards, therefore providing a great enhancement to the general probiotics market growth.

Challenges associated with the development of the probiotics market

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Even though there is a general optimistic outlook of the probiotics market, there are a number of issues centred around the regulations of probiotic products. Several scientists have pointed out the unpredictable quality of some over-the-counter probiotic supplements, whereby these products do not always contain the medically recognised probiotic strains. This is due to these bacteria having been killed during the manufacturing process.  

In contrast, there is an abundance of research areas that needs to be conducted in order to gain a complete overview of the application of these probiotics. Dr Martin Blaser, who is a microbiologist working with the NYU Medical Centre announced his support for a Gut Genome Project, which is to be similar to the renowned Human Genome Project. This is mainly because even if a huge amount of funding is required to finance this initiative, such study could be a vital component towards the discovery of essential factors for better product development.

In addition to that, the emerging and ever-advancing omics technologies might assist researchers in gaining a more in-depth knowledge of the complex interactions and processes that occur between the human host and the probiotic bacterial species. Nevertheless, this is under the condition that the research plan has been properly designed so that the data obtained is of high quality with sufficient biological implications towards the scientific community to offer ideas for future steps.

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Final conclusions

The probiotics industry is an emerging entity although its current infancy stage. It presents numerous opportunities for a greater range of products, especially because these opportunistic endpoints have not yet been achieved, especially due to the lack of credible health claims for these probiotic products. 

Ultimately, the immense market potential is an attractive research area for scientists to venture into, with the hopes of identifying the exact strains of probiotics that play a direct role in improving human health and eradicating diseases. 

Verified by a Healthcare Professional

Anastasiia Myronenko

Anastasiia Myronenko

Anastasiia Myronenko is a Medical Physicist actively practicing in one of the leading cancer centers in Kyiv, Ukraine. She received her master’s degree in Medical Physics at Karazin Kharkiv National University and completed Biological Physics internship at GSI Helmholtz Centre for Heavy Ion Research, Germany. Anastasiia Myronenko specializes in radiation therapy and is a fellow of Ukrainian Association of Medical Physicists.

 

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