Role of Multi-strain Probiotics in Gut Dysbiosis Associated with Long-term Use of Medications in Chronic Diseases: Practical Review

The negative impact of antibiotics on the gut microbiota has been well-established. Studies have also identified the relationship between multiple groups of drugs and gut micro-biome signatures. Proton-pump inhibitors, metformin, and laxatives show the strongest associations with the microbiome. (2)

Impact of Commonly Used Drugs Influencing the Gut Microbiome (3)

Proton pump inhibitors: PPIs were among the pharmacological class of agents most strongly linked to a decline in diversity and alterations in the taxonomy of the gut microbiome. Studies have revealed that the relative abundance of up to 20% of bacterial taxa was altered (either decreased or increased) in PPI users compared to non-users. Analysis of faecal samples among PPI users showed a lower microbial diversity and lower abundance of gut commensals. (3)

The taxonomic alterations in PPI users' feces indicate a decrease in commensal bacteria in the colon and a rise in bacteria from the oral cavity. This shift towards typical oral bacteria is reflected by an increase in the species Rothia dentocariosa and Rothia mucilaginosa, the genus Actinomyces, and the family Micrococcaceae. Ruminococcaceae and Bifidobacteriaceae have decreased, and the families Enterobacteriaceae, Enterococcaceae, and Lactobacillaceae have increased. Furthermore, considering that omeprazole, esomeprazole, and pantoprazole all displayed comparable alterations, the observed changes represent a class effect of PPIs. Greater microbial alterations also appear to be linked to higher dosages of PPI use. (3)

Metformin: Metformin is an oral blood-glucose-lowering agent widely used to treat type 2 diabetes. It reduced the abundance of genus Intestinibacter, which aligns with findings from cross-sectional cohorts that compared untreated patients to metformin-treated patients with type 2 diabetes. In another interventional study in healthy volunteers, metformin resulted in a change in >80 species compared with a control group receiving a placebo. Notably, metformin treatment significantly increases Escherichia coli. (3)

Other Commonly Used Non-Antibiotic Drugs: In addition to the above commonly used drugs, other agents such as laxatives, statins, antidepressants, and opioids, also caused changes in gut microbiome composition. (3) Among NSAIDs, aspirin significantly modified the composition of bacterial communities within the gut microbiome. Higher abundance in genus Prevotella was reported among six-week course users of aspirin, along with an increase of Clostridium XIVa cluster and a decrease in Akkermansia, and Clostridium XVIII cluster. (4)

Probiotics in the Treatment of Gut Dysbiosis Associated with Chronic Disease:

Several therapeutic strategies targeting the gut microbiome are available. Probiotics are becoming popular for health benefits given the quest for safer products with protective and therapeutic effects against chronic diseases and infectious agents. (5)

How do Probiotics work?: The proposed probiotic mechanisms include an influence on the composition and function of the gut microbiome. Probiotics generate substances that inhibit the development of other bacteria or compete with other intestinal microbes for receptors and binding sites on the intestinal mucosa. Genus Lactobacillus-containing probiotics improve intestinal barrier integrity, which may lead to immunological tolerance, maintenance, and reduced bacterial translocation across the intestinal mucosa. (6)

Choice of Probiotics- Mono-strain or Multistrain?

The effectiveness of probiotic treatments might vary depending on whether they include one or many strains. Multistrain probiotic preparations, instead of single-strain, include numerous strains of the same species, genera, or multiple genera, and occasionally bacteria and fungus (Saccharomyces species). Research indicates that some multistrain probiotics might demonstrate superior inhibitory effects on entero-pathogens and increased benefits by combining the potentially complementary actions of several strains. (5)

A review article noted that several multistrain probiotics, both with and without prebiotics, effectively modify the gut microbiota to a more advantageous population and inhibit pathogens that can multiply and infect the gut. (7)

Cell-cell contact, interactions with host tissues, and immune system modification are ways multistrain probiotics could exert their effects. (5) Multi-strain probiotics have synergistic effects and achieve greater efficacy due wider variety of strains at the same concentration. (7)

Multi-Strain Probiotics Benefits Risk Associated with PPI Use:

A randomized, double-blind, placebo-controlled study analyzed the potential role of multi-strain probiotic intervention in mitigating untoward effects of PPIs such as gut dysbiosis. The patients (n=30) were administered either PPIs (n = 15) or placebo (n = 15) over 6 weeks. The results showed that multi-strain probiotics inhibited PPI-induced microbial changes such as a decrease in Leuconostacaceae family (p = 0.01) and led to an increase in metabolite 1H-Indole-4-carbaldehyde. The study concluded that probiotic supplementation suppresses PPI-induced microbial alterations and thus mitigates potential risks associated with PPI-mediated perturbation of the microbial community. (8)

Clinical Care Points

• Chemical compounds present in commonly used drugs for chronic disease extensively impact gut bacteria.
• Among commonly used drugs, proton-pump inhibitors, metformin, antibiotics, and laxatives show the strongest associations of alterations in the microbiome.
• Probiotics may restore the composition of the gut microbiome and introduce beneficial functions to gut microbial communities, resulting in the amelioration or prevention of gut inflammation and its related intestinal or systemic disease phenotypes.
• Probiotics represent a promising approach to improving human health and supporting to prevent and treat several diseases of clinical interest.
• Multiple studies have suggested that probiotic mixtures are effective against various host-related diseases, implying that combining various probiotic microorganisms in a single formulation can provide greater protection against many intestinal pathogens compared to monostrain formulations. (7)

The above article has been published by Medical Dialogues under the MD Brand Connect Initiative. For more details on Probiotics, click here.

Reference:

1. Vijay, A., Valdes, A.M. Role of the gut microbiome in chronic diseases: a narrative review. Eur J Clin Nutr 76, 489–501 (2022). https://doi.org/10.1038/s41430-021-00991-6

2. Vich Vila A, Collij V, Sanna S, et al. Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nat Commun. 2020;11(1):362. Published 2020 Jan 17. doi:10.1038/s41467-019-14177-z

3. Weersma RK, Zhernakova A, Fu J Interaction between drugs and the gut microbiome Gut 2020;69:1510-1519.

4. Le Bastard Q, Berthelot L, Soulillou JP, Montassier E. Impact of non-antibiotic drugs on the human intestinal microbiome. Expert Rev Mol Diagn. 2021;21(9):911-924. doi:10.1080/14737159.2021.1952075

5. Kwoji ID, Aiyegoro OA, Okpeku M, Adeleke MA. Multi-Strain Probiotics: Synergy among Isolates Enhances Biological Activities. Biology (Basel). 2021;10(4):322. Published 2021 Apr 13. doi:10.3390/biology10040322

6. Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol. 2013;6(1):39-51. doi:10.1177/1756283X12459294

7. Chapman CM, Gibson GR, Rowland I. Health benefits of probiotics: are mixtures more effective than single strains?. Eur J Nutr. 2011;50(1):1-17. doi:10.1007/s00394-010-0166-z

8. Singh G, Haileselassie Y, Briscoe L, et al. The effect of gastric acid suppression on probiotic colonization in a double-blinded randomized clinical trial. Clin Nutr ESPEN. 2022;47:70-77. doi:10.1016/j.clnesp.2021.11.005