Consumers and Health

Probiotics, a solution for chronic inflammation

December 6, 2022

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Probiotics have recently emerged as a potential dietary approach to fight inflammation, modulate immune response and prevent the onset of chronic gut diseases.

Chronic inflammatory diseases are the most significant cause of death to date, accounting for more than 50 percent of all deaths. They are involved in ischemic heart disease, stroke, cancer, diabetes mellitus, chronic kidney disease, nonalcoholic fatty liver disease (NAFLD), and autoimmune and neurodegenerative conditions.

Table of Contents

Causes of the inflammatory process

Inflammation is a process characterized by the activation of immune and nonimmune cells that protect the host from bacteria, viruses, and toxins by eliminating pathogens and promoting tissue repair and recovery. The illness or ‘energy-saving’ behaviors of inflammation are sadness, anhedonia, fatigue, reduced libido and food intake, impaired sleep and social-behavioral withdrawal, as well as increased blood pressure, insulin resistance and dyslipidemia (1).

A normal inflammatory response is characterized by a temporally limitedup-regulation of inflammatory activity in the presence of threat. However, the presence of certain social, psychological, environmental, and biological factors is linked to the prevention of acute inflammation and, in turn, the promotion of a low-grade, noninfectious (i.e., ‘sterile’) state of Chronic Systemic Inflammation (SCI), with activation of immune components distinct from those engaged during the acute immune response.

The factors that most elevate the level of systemic inflammation, depicted on the left in Figure 1 (1), can be varied including an unbalanced diet rich in sugars, refined flours, trans and saturated fats (2).

Effects of the inflammatory process

The consequences of intestinal inflammation do not only affect the digestive system. One study (3) identified bacterial lipopolysaccharide (LPS) as an inflammatory factor causing insulin resistance, obesity, and diabetes. LPS is a small molecule that increases as a result of changes in the gut microbiome due to a high-fat diet, and its potential relevance in the clinical setting is to provide a target for controlling metabolic diseases.

probiotics useful against inflammation — Figure 1 – Shown are, on the left, the most common triggers of SCI (counterclockwise), and on the right, the consequences of SCI (clockwise) (1).

The transition of the inflammatory response from short to long duration can cause a breakdown in immune tolerance and lead to alterations in tissues and organs as well as normal cell physiology. In addition, SCI during pregnancy and childhood can have serious developmental consequences, including increased risk of noncommunicable diseases throughout life.

Inflammation and the digestive system

There is a delicate balance between the human immune system and the gut microbiota, which can be disrupted by various factors that increase the level of chronic inflammation and induce dysbiosis.

Many diseases of the gastro-intestinal system (IBS, ulcerative colitis, Crohn’s disease, etc.) share a very high level of chronic inflammation, driven mainly by M1 macrophages, immune response molecules in charge of maintaining tissue homeostasis, regulating inflammation and playing a significant role in host protection (4).

Chronic systemic inflammation (SCI) in the IBS patient causes reactions by the immune system, in a state of over-stimulation, even for common foods, which are perceived as harmful or pathogenic. These immune reactions then cause the characteristic abdominal pain, accompanied by the rest of the symptomatology typical of the syndrome.

Anti-inflammatory effects of probiotics on chronic intestinal diseases

Consumption of probiotics has several beneficial effects on the gastrointestinal system (5).

Through preliminary studies (6), some of the mechanisms by which specific probiotics may play a role in modulating the immune system and anti-inflammatory response in the treatment of chronic intestinal inflammation have been demonstrated (7).

The use of the multi-strain formulation of Lactobacillus rhamnosus, Bifidobacterium lactis, and Bifidobacterium longum accelerates the anti-inflammatory process by inducing significant down-regulation of pro-inflammatory cytokines (IL-1b and IL-6) and indirectly modulates proinflammatory immune responses of macrophages. This is due to the transformation of the M1 (inflammatory) to M2 (tissue regenerative, anti-inflammatory activity) macrophage phenotype induced precisely by the passage of metabolites produced by the probiotic formulation used, across the intestinal mucosal barrier.

The immunomodulatory action of probiotics is therefore a key piece in pointing to them as a treatment for chronic intestinal inflammation.

An additional beneficial effect on the body related to the use of probiotics is the promotion of healthy aging (8).

Aging, in fact, is accompanied by biological changes among which we see two of the predominant phenomena: chronic low-grade inflammation(inflammaging) and changes in the composition of the gut microbiota (dysbiosis). The use of probiotic products (single-strain or mixtures) can modulate these phenomena through the production of short-chain fatty acids (SCFA, the main metabolites produced by bacterial fermentation of dietary fiber) and the immunomodulatory action described earlier.

Conclusions

In the treatment of Irritable Bowel Syndrome (IBS), the use of probiotics and prebiotics can positively influence the microbiome, both in terms of species and number of microorganisms, causing a decrease in pro-inflammatory species, resulting in a decrease in the production of cytokines (inflammatory molecules) and a reduction in the level of chronic inflammation.

The use of probiotics and prebiotics for patients suffering from diseases related to intestinal dysbiosis is indicated both in a ‘preventive’ form, to maintain a good intestinal balance, and in an ’emergency’ form, to intervene at times when the pathology tends to exacerbate (highly stressful periods, seasonal changes, changes in daily diet, alterations in sleep hygiene, etc.).

Giulia Pietrollini

Notes

(1) Furman, D., Campisi, J., Verdin, E. et al. Chronic inflammation in the etiology of disease across the life span. Nat Med 25, 1822-1832 (2019). https://doi.org/10.1038/s41591-019-0675-0

(2) Marta Strinati. The role of ultraprocessed foods in inflammatory bowel disease. GIFT (Great Italian Food Trade). 15.11.22

(3) P. D. Cani, J. Amar, M. Iglesias, M. Poggi, C. Knauf, D. Bastelica, A. M. Neyrinck, F. Fava, K.Tuohy, C. Chabo, Aurélie Waget, E. Delmée, B. Cousin, T. Sulpice, B. Chamontin, J. Ferrières, J-F. Tanti, G. R. Gibson, L. Casteilla, N. Delzenne, M. Alessi, Rémy Burcelin; Metabolic Endotoxemia Initiates Obesity and Insulin Resistance. Diabetes 1 July 2007; 56 (7): 1761-1772. https://doi.org/10.2337/db06-1491

(4) Han Xuebing, Ding Sujuan, Jiang Hongmei, Liu GangRoles of Macrophages in the Development and Treatment of Gut Inflammation, Frontiers in Cell and Developmental Biology Vol.9 (2021) doi:10.3389/fcell.2021.625423

(5) Dario Dongo, Carlotta Suardi. Prebiotics and probiotics, microbiome and immune system. GIFT (Great Italian Food Trade). 28.4.20

(6) M. Sichetti, S. De Marco, R. Pagiotti, G. Traina, D. Pietrella, Anti-inflammatory effect of multistrain probiotic formulation (L. rhamnosus, B. lactis, and B. longum), Nutrition, Volume 53, 2018, Pages 95-102, ISSN 0899-9007, doi.org/10.1016/j.nut.2018.02.005.

(7) Plaza-Díaz, J.; Ruiz-Ojeda, F.J.; Vilchez-Padial, L.M.; Gil, A. Evidence of the Anti-Inflammatory Effects of Probiotics and Synbiotics in Intestinal Chronic Diseases. Nutrients 2017, 9, 555. https://doi.org/10.3390/nu9060555

(8) Warman, D.J.; Jia, H.; Kato, H. The Potential Roles of Probiotics, Resistant Starch, and Resistant Proteins in Ameliorating Inflammation during Aging (Inflammaging). Nutrients 2022, 14, 747. https://doi.org/10.3390/nu14040747