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Why gut health probiotics require an integrated approach
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Why an integrated approach is critical for gut health probiotics

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Digestive health is a cornerstone of the European probiotic market.

Valued at $14.1 billion (€13 billion) in 2023, the market is forecast to achieve a compound annual growth rate of 7.3% by 2030.1​ Yet, while demand is strong, most products are too narrowly targeted to realise the full benefits of the range of validated strains now available.

To unleash the true power of probiotics, manufacturers and brand owners should adopt an integrated approach to gut health that harnesses the benefits of bacterial strains.

Most gut health probiotics target irritable bowel syndrome (IBS) and diarrhoea. An integrated approach could meet the needs of a broader range of consumers. One poll showed gut health is a concern for 80% of adults in Europe.2​ Another survey found 67% of millennials in the UK had experienced bloating, diarrhoea or constipation in the past year.3

The figures may reflect changing lifestyles. Seeking to consume healthy diets, people are eating more vegetables and increasing their intake of fibre. Such diets have many health benefits but increased consumption of oxalates and gluten can cause digestive problems.

Probiotics can help. Working with Probiotical, manufacturers and brand owners can access validated strains that target the absorption and digestion of nutrients, mitigate intolerances, modulate gut permeability and enhance gut homeostasis.

Adopting an integrated approach to gut health, companies can combine strains into custom probiotics tailored to the specific needs of different populations. Here, we look at the evidence on strains in four key areas of digestive health to explore the potential for custom products.

Mitigating gluten’s effects

Gliadin, a component of the protein gluten, plays a central role in the biological pathway that is activated when a person with coeliac disease consumes wheat, rye or barley. The gluten component triggers the disassembly of tight junctions, enabling it to cross the epithelial barrier and activate the immune cells that cause coeliac symptoms.

Studies suggest probiotics may affect coeliac disease by modulating intestinal permeability, regulating the immune system and acting on the digestion of certain peptides. Researchers tested a blend of two strains of Bifidobacterium breve​, B632 and BR03, in three randomised, placebo-controlled clinical trials.

In one study, children with coeliac disease received the B. breve​ blend or placebo.4​ After three months, levels of the pro-inflammatory cytokine TNF-alpha fell in the probiotic arm. Levels of the cytokine, which is implicated in damage to the intestinal mucosa, rebounded after subjects stopped taking the probiotic.

Like the first study, the second trial randomised children with coeliac disease to receive the B. breve​ blend or placebo for three months.5​ The trial revealed a strong correlation between TNF-alpha and types of bacteria and archaea.

The third trial also randomised children with coeliac disease to receive the B. breve​ blend or placebo for three months.6​ Investigators took microbial DNA from subjects’ faeces at baseline and after treatment. Participants had a reduced Firmicutes:Bacteroidetes ​ratio and low levels of Actinobacteria​ at baseline.

After three months, the researchers saw an increase in Actinobacteria​ and the re-establishment of the physiological Firmicutes:Bacteroidetes​ ratio. The investigators concluded the blend helps in restoring the healthy percentage of the main microbial components.

Another group generated insights into how the blend may act on coeliac disease by studying the strains in a mouse model of gluten sensitivity.7​ The study showed the probiotics reduced the unfolded protein response (UPR) and gut inflammation. Gliadin induced endoplasmic reticulum stress, driving activation of UPR linked to inflammatory diseases including coeliac, but probiotics mitigated the cellular response.

Collectively, the studies suggest the probiotic blend can counteract the detrimental effects of gliadin on the intestinal epithelial structure and enhance gluten digestion. The positive effects could make it easier for people with coeliac disease or gluten sensitivity to cope with symptoms following gluten intake.

Restoring intestinal homeostasis

Multiple studies have shown the gut microbiota affects intestinal homeostasis. Other studies have found probiotics may be able to protect intestinal epithelial integrity and host homeostasis. The research led to an assessment of the effect of Lacticaseibacillus rhamnosus​ LR04 and Lacticaseibacillus casei ​LC03 in animal models.8 

The study showed the three strains have the potential to restore barrier function by increasing mucus production, restoring normal permeability and modulating colonic hypersensitivity. LR04 was one of the most promising strains. Analysing expression of junctional proteins, the researchers implicated Claudin 2 and Cingulin in the interactions between the strains and the host.

Another study showed the effect of two probiotic blends on mouse colon tissue that was exposed to a substance that causes compromised tight junction organisation and other hallmarks of IBS.9​ One blend consisted of B. breve ​B632 and BR03. The other blend was made of LR04, Lactiplantibacillus plantarum​ LP14 and Lacticaseibacillus paracasei​ LPC09.

Both probiotic formulations completely prevented detrimental effects, including the deregulation of tight junction proteins, providing further evidence of the potential for probiotics to counter drivers of gut health problems. Other researchers looked at the effect of various strains on in vitro ​models of intestinal permeability, linking LR04 to the protection of mature enterocytes of the small intestine.10

Increasing mineral absorption

A growing body of evidence suggests probiotic strains can increase mineral absorption and improve mineral status. One study assessed the use of the postbiotic heat-treated bacteria Lactobacillus buchneri​ LB26 and Bifidobacterium lactis​ BB1 to internalise selenium and zinc.11

Absorption of selenium and zinc accumulated intracellularly by the two strains was significantly higher than for the organic forms of the minerals, suggesting the bacteria can play a role in overcoming the bioavailability problems that contribute to micronutrient deficiencies.  

Another study showed supplementation with Bifidobacterium lactis​ BS01 and Lactobacillus acidophilus ​LA02 may change the mineral balance in healthy young women.12​ The randomised, placebo-controlled trial linked supplementation with the probiotic blend to increases in calcium, magnesium and iron.

Supporting oxalate metabolism

There are well-established health benefits to eating a diet that is rich in vegetables. However, increasing consumption of vegetables, particularly some types such as beetroot and spinach, also results in people ingesting more oxalate.13​ Humans lack enzymes to directly metabolise the molecule. As levels of oxalate rise, the molecule can combine with calcium to form kidney stones and cause health problems.

Certain bacteria found in humans degrade oxalate but their levels vary significantly between individuals.14​ Recognising the potential for probiotics to improve oxalate degradation, researchers assessed a panel of 13 lactobacilli and five bifidobacteria.

The study showed Lactobacillus​ strains were more efficient than bifidobacteria in degrading oxalates. L. paracasei​ LPC09 was the most efficient of the studied strains, converting 68.5% of ammonium oxalate in the study. The researchers showed L. acidophilus​ LA02 and L. plantarum​ LP01 were effective degraders too, creating opportunities to combine those strains with LPC09 to achieve the best results.

Creating custom probiotics

Probiotical’s long-standing commitment to the validation of probiotics has created a portfolio of strains with proven effects on a range of drivers of gut health. The portfolio supports the development of custom products that are aligned with the needs of the vast numbers of European consumers who have digestive issues.

Researchers have shown the potential of strains to help reduce the bloating and inflammation that can affect many consumers of Western diets rich in gluten. In parallel, studies have validated the effects of other strains on the metabolism of oxalates, intake of which could increase as people adopt vegetarian, vegan and flexitarian diets. Probiotical’s strains are completely free from animal derivatives.

The multitude of validated effects of Probiotical’s strains empowers companies to create products that target the specific needs of different groups of consumers. By working with Probiotical to develop such custom products, manufacturers and brand owners can better serve the millions of Europeans with gut health issues and drive the continued growth of a large probiotic market.

References

1. ​Grand view research. Europe Digestive Health Products Market Size, Share & Trends Analysis Report By Product (Dairy Products, Bakery & Cereals), By Ingredient (Prebiotics, Probiotics), And Segment Forecasts, 2024 – 2030.
2. ​Sensus. Results consumer survey 2023 | Gut health a major concern.
3. ​Kellogg’s. GENERATION GUT: Stomach issues are affecting more than just the body as three quarters of millennials say their gut health has a direct impact on their emotional wellbeing, new research reveals.
4. ​Klemenak, M.; Dolinšek, J.; Langerholc, T.; et al. (2015). Administration of Bifidobacterium breve Decreases the Production of TNF-α in Children with Celiac Disease.​ Digestive diseases and sciences. 60(11), 3386–3392.
5. ​Primec, M.; Klemenak, M.; Di Gioia, D.; et al. (2019). Clinical intervention using Bifidobacterium strains in celiac disease children reveals novel microbial modulators of TNF-α and short-chain fatty acids.​ Clinical nutrition (Edinburgh, Scotland). 38(3), 1373–1381.
6. ​Quagliariello, A.; Aloisio, I.; Bozzi Cionci, N.; et al. (2016). Effect of Bifidobacterium breve on the Intestinal Microbiota of Coeliac Children on a Gluten Free Diet: A Pilot Study.​ Nutrients. 8(10), 660.
7. ​Ferrari, E.; Monzani, R.; Saverio, V.; et al. (2021). Probiotics Supplements Reduce ER Stress and Gut Inflammation Associated with Gliadin Intake in a Mouse Model of Gluten Sensitivity.​ Nutrients. 13(4), 1221.
8. ​Chamignon, C.; Mallaret, G.; Rivière, J.; et al. (2023). Beneficial Effects of Lactobacilli Species on Intestinal Homeostasis in Low-Grade Inflammation and Stress Rodent Models and Their Implication in the Modulation of the Adhesive Junctional Complex.​ Biomolecules. 13(9), 1295.
9. ​Monzani, R.; Gagliardi, M.; Clemente, N.; et al. (2022). The Gut-Ex-Vivo System (GEVS) Is a Dynamic and Versatile Tool for the Study of DNBS-Induced IBD in BALB/C and C57BL/6 Mice, Highlighting the Protective Role of Probiotics.​ Biology. 11(11), 1574.
10. ​Chamignon, C.; Guéneau, V.; Medina, S.; et al. (2020). Evaluation of the Probiotic Properties and the Capacity to Form Biofilms of Various Lactobacillus Strains.​ Microorganisms. 8(7), 1053.
11. ​Mogna, L.; Nicola, S.; Pane, M.; et al. (2012). Selenium and zinc internalized by Lactobacillus buchneri Lb26 (DSM 16341) and Bifidobacterium lactis Bb1 (DSM 17850): improved bioavailability using a new biological approach.​ Journal of clinical gastroenterology. 46 Suppl, S41–S45.
12.​ Czajeczny, D.; Wójciak, R.; Czajeczny, D.; et al. (2021). Bifidobacterium lactis BS01 and Lactobacillus acidophilus LA02 supplementation may change the mineral balance in healthy young women.J. Elem.
13.​ Noonan, S. C., & Savage, G. P. (1999). Oxalate content of foods and its effect on humans.​ Asia Pacific journal of clinical nutrition, 8(1), 64–74.
14.​ Mogna, L.; Pane, M.; Nicola, S.; et al. (2014). Screening of different probiotic strains for their in vitro ability to metabolise oxalates: any prospective use in humans?.​ Journal of clinical gastroenterology. 48 Suppl 1, S91–S95.

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