These include cardiovascular disease, neurological disorders (Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis), cancer, rheumatoid arthritis, type 1 diabetes, and inflammatory bowel diseases among many others.1,3
Classification of dysbiosis
Dysbiosis is characterised by bacterial overgrowth in the small intestine due to reduced gastric acid production with an excess of bacterial fermentative activity. However, it is not a single condition. Dysbiosis is classified as:4,5
Deficiency dysbiosis: a condition characterised by an overall reduction of beneficial bacterial species (such as lactobacilli and/or bifidobacteria), which can occur as a consequence of unhealthy diets or antibiotic therapies, and can be associated with food intolerances consequent to a deficiency in digestive enzymes (intolerance to milk or meat)
Putrefactive dysbiosis: characterised by an increase in putrefactive bacteria (mainly Bacteroides), generally results from a diet rich in fat and meat and poor in fibre, the metabolisation of which can lead to products such as ammonia, amines, and phenols, which could be the cause of symptoms not limited to the gastrointestinal (GI) tract but that can also affect the entire body
Fermentative dysbiosis: often affects patients with irritable bowel syndrome, patients who receive antibiotic treatment, and those who reduce carbohydrate consumption
Susceptibility dysbiosis: associated with a lost tolerance of intestinal microbiota in which genetic causes (leading to abnormal immune responses towards components of the gut microbiota) play an important role and are linked to IBD and other similar diseases. In susceptibility dysbiosis, alterations to the gut microbiota ecosystem are characterised by reduced probiotic bacteria, an increase in potentially pathogens microbes (pathobionts), altered motility of the intestine, and bowel inflammation.
Fungal dysbiosis: characterised by the overgrowth of Candida or other fungal species in the gut microbiota, is promoted by a diet rich in sugar and low in fibres.
ICU dysbiosis: alterations in intestinal homeostasis and gut microbiota in critical illness have been associated with increased inflammatory cytokine production, gut barrier dysfunction, and increased cellular apoptosis. According to Wischmeyer et al loss of ‘health-promoting’ microbes and dysbiosis in the intensive care unit (ICU) is believed to contribute to nosocomial infections, sepsis, and organ failure (multiple organ dysfunction syndrome). Studies show that ICU dysbiosis can be caused by a number of factors including the overuse of antibiotics.
Restoring the gut microbiome balance
Probiotics are defined as ‘live microorganisms that, when administered in adequate amounts, confer a health benefit on the host’. It is now well established that probiotics can modulate the gut microbiota of the host in a beneficial fashion.6
Probiotics can be used both to prevent the onset of dysbiosis when the patient is exposed to predisposing conditions (prolonged antibiotic therapies, intense physical or mental stress, chronic debilitating diseases) and as therapeutic agents to rebalance an ongoing condition of dysbiosis.5
Probiotic strains should:5
- Belong to species that form normal components of our gut microbiota
- Belong to the group of microorganisms designated generally regarded as safe (GRAS), even for immune-compromised patients
- Prove to stay active and vital (for a reasonable period) in the intestinal environment
- Resist when exposed to the gastric environment (bile and pancreatic secretions).
Human indigenous strains certainly possess adaptive traits, which allow them a stable colonisation and more effective and lasting beneficial effects. Beneficial effects of probiotic strains can be categorized as:5
Immunological: benefits include the activation of local macrophages, an increase in the production of immunoglobulin, the modulation of cytokine profiles, and the induction of hypo-response to food antigens
Non-immunological: benefits include the digestion process, competition with potential pathogens for nutrients and intestinal adhesion sites, pH alterations, and bacteriocins production.
Lactobacillus reuteri, the most studied probiotic, is a strain of lactic acid bacteria that live in the intestines, and occasionally the stomachs of humans, other mammals, and birds.6
L. reuteri can colonise different human body sites, including primarily the GI tract.
Recently, the interest in this probiotic has significantly increased thanks to its properties in the prevention and in the treatment of numerous GI symptoms and disorders, both in children and in adults.7
L. reuteri adheres to the intestinal epithelium, producing proteins able to bind with the mucus, making it tough for pathogen microorganisms to enter, and thereby remodelling the balanced composition of gut microbiota.7
Moreover, L. reuteri produces antimicrobial molecules and promotes the development and the functionality of regulatory T cells, strengthening the gut barrier, and decreasing the microbial translocation from the intestinal lumen to the tissue, as reported by studies conducted on animal models, on humans and in vitro.7
Literature preclinical studies, using genetic tools such as genome sequencing, molecular tools, and genomic-based approaches (both in mice and then in humans) showed that L. reuteri has multiple beneficial effects on GI symptoms, on gut infections, Helicobacter pylori eradication, antibiotic-associated diarrhoea, inflammatory bowel syndrome, inflammatory bowel disease, and colorectal cancer.7
It can reduce abdominal pain in infantile colic, the functional abdominal discomfort in children, and it can decrease crying due to necrotising enterocolitis in preterm neonates. It can improve gut motility and chronic constipation as demonstrated in infants, with beneficial effects on patients’ disorders.7
Studies also show that L. reuteri may be beneficial in the management of atopic dermatitis (AD) in children and hypercholesterolemia in adults.8,9
According to Wischmeyer et al, probiotics should be considered to prevent infection in ICU. Beneficial effects of probiotic interventions have been shown to include induction of host cell antimicrobial peptides, release of antimicrobial factors, suppression of the immune cell proliferation, stimulation of mucus and IgA production, antioxidative activity, inhibition of epithelial cell nuclear factor k-B activation, prevention of gut apoptosis, and other epithelial barrier protective effects.5
According to Manzoor et al, the interaction between the microflora-gut-brain axis has a profound effect on brain function, thereby influencing the overall well-being of an individual. Probiotics have evolved as promising therapeutic techniques to treat several disease conditions associated with the GI tract.10
1. Lozupone CA, Stombaugh JI, Gordon GI, et al. Diversity, stability, and resilience of the human gut microbiota. Nature, 2012.
2. Chatterjee R, Shreenivas MM, Sunil R and Chakravortty D. Enteropathogens: Tuning Their Gene Expression for Hassle-Free Survival. Frontiers in Microbiology, 2019.
3. Martinez JE, Kahana DD, Ghuman S, et al. Unhealthy Lifestyle and Gut Dysbiosis: A Better Understanding of the Effects of Poor Diet and Nicotine on the Intestinal Microbiome. Front Endocrinol, 2021.
4. Gagliardi A, Totino V, Cacciotti F, et al. Rebuilding the Gut Microbiota Ecosystem. Int J Environ Res Publich Health, 2018.
5. Wischmeyer PE, McDonald D, Knight R, et al. Role of the microbiome, probiotics, and ‘dysbiosis therapy’ in critical illness. Critical Care, 2016.
6. Milner E, Stevens B, An M, et al. Utilizing Probiotics for the Prevention and Treatment of Gastrointestinal Diseases. Frontiers Microbiology, 2021.
7. Saviano A, Brigida M, Migneco A, et al. Lactobacillus Reuteri DSM 17938 (Limosilactobacillus reuteri) in Diarrhea and Constipation: Two Sides of the Same Coin? Medicina, 2021.
8. Mu Q, Tavella VJ, Luo XM, et al. Role of Lactobacillus reuteri in Human Health and Diseases. Front Microbiol, 2018.
9. Jones ML, Martoni CJ, Prakash S, et al. Cholesterol lowering and inhibition of sterol absorption by Lactobacillus reuteri NCIMB 30242: a randomized controlled trial. European Journal of Clinical Nutrition, 2012.
10. Manzoor S, Wani SM, Mir SA and Rizwan D. Role of probiotics and prebiotics in mitigation of different diseases. Nutrition, 2022.