The educational content in this post, elaborated in collaboration with Bromatech, was independently developed and approved by the GMFH publishing team and editorial board.

When inflammation becomes a public health enemy

Acute inflammation that is limited in time contributes to healing, removing threatening invaders and repairing tissue. However, when inflammation becomes chronic, it can lead to cardiovascular disease, diabetes, chronic kidney disease and autoimmune and neurodegenerative disorders, among others. On 23 February 2004, TIME magazine dedicated its cover to chronic inflammation with the provocative title “The Secret Killer”, to highlight the threat to human health that inflammation poses.

Physical inactivity, an unbalanced diet, xenobiotics, infections and an altered gut microbiome are the main triggers of persistent inflammation that, despite being silent, can impair the normal functions of body cells and tissues if it does not resolve. The process of aging has also been linked to systemic chronic inflammation, which is related to frailty and a higher risk of chronic ailments.


The link between gut health and inflammation

The dialogue between the gut microbiome, the gut barrier and immune cells in the underlying lamina propria is important in keeping inflammation in the gut at bay. However, when any of those protective mechanisms do not work properly, it can lead to an uncontrolled inflammatory response.

Inflammation is common in digestive diseases and manifests in multiple ways. For instance, Crohn’s disease and ulcerative colitis may emerge due to an excessive immune response—mainly driven by M1 or pro-inflammatory macrophages—to the harmless microbiome. On the other hand, abdominal pain seen in irritable bowel syndrome might have its roots in localized immune responses in the gut that cause common foods to be perceived as harmful.

The consequences of intestinal inflammation also go beyond the gut. Patrice Cani and colleagues discovered the role of bacterial lipopolysaccharide (LPS) as a triggering factor involved in the onset of obesity. LPS is a small molecule that increases secondary to changes in the gut microbiome due to a high-fat diet, and its potential relevance in the clinical setting is providing a target for controlling metabolic diseases.


Evidence of the anti-inflammatory effects of probiotics on chronic intestinal diseases and beyond

Diet, mainly due to the content of polyphenols and antioxidant vitamins and minerals found in plant foods, is one of the most widely studied modifiable factors for combating chronic inflammation.

More recently, probiotics have emerged as a potential dietary approach for fighting off inflammation. One of the main mechanisms behind the immune system-related benefits of probiotics studied in in vitro and animal studies is that of restoring the epithelial barrier.

Based on the findings of an in vitro study using the Transwell® model as a novel approach to studying the human epithelial barrier, Professor Giovanna Traina from the University of Perugia explained via email to GMFH editors some mechanisms by which specific probiotics can have a role in immune system modulation and the anti-inflammatory response.

“The multistrain formulation of Lactobacillus rhamnosus, Bifidobacterium lactis and B. longum had the ability to accelerate the anti-inflammatory process following inflammation, inducing a significant down-regulation of the pro-inflammatory cytokines IL-1b and IL-6, and is able to modulate indirectly the immune proinflammatory responses of macrophages,” acknowledges Prof. Traina.

But how do the immunomodulatory effects of probiotics translate to the bedside?

In the context of digestive diseases, randomized controlled trials have shown that specific probiotics and synbiotics, including monospecies and mixtures of Bifidobacterium, Lactobacillus, Streptococcus and Clostridioides species, can reduce the inflammatory potential of the gut microbiome in patients with mild to moderately active ulcerative colitis and patients already in remission. In contrast, the role of probiotics in preventing the recurrence of Crohn’s disease is controversial.

Based on preliminary findings presented by Prof. Traina, one mechanism that might explain the potential therapeutic relevance of probiotics in chronic intestinal diseases is the switch of macrophage phenotype M1 (inflammatory) to M2 (tissue-regenerative, anti-inflammatory activity) induced by the passage of probiotic formulation metabolites through the mucosa barrier, although other mechanisms can probably operate within the body after administering the probiotic.

Probiotics have also been shown to promote healthy aging by indirectly mitigating age-related inflammation. That is done by promoting short-chain fatty acid production or directly reducing the production of pro-inflammatory molecules by immune cells.

According to Prof. Traina: “Probiotic products made of multi-strain or multi-species probiotic blends, in which each strain has an additive or synergistic effect with the others, can lead to greater efficacy for the health of the host.”


Take-home messages

  • Inflammation is needed for human survival, but when it is perpetuated over time can increase the risk of chronic diseases.
  • Probiotics emerge as potential tools for fighting off inflammation that can contribute to alleviating chronic intestinal diseases and may be a preventive strategy to support healthy aging.
  • The restoration of the mucosal barrier to pathogens is one of the most widely studied mechanisms by which probiotics might counteract gut inflammation.




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