Lipopolysaccharides (LPSs) are bacterial surface glycolipids, produced by Gram-negative bacteria. LPS is known to determine acute inflammatory reactions, particularly in the context of sepsis. However, LPS can also trigger chronic inflammation. In this case, the source of LPS is not an external infection, but rather an increase in endogenous production, which is usually sustained by gut microbiota (GM), and LPS contained in food. The first site in which LPS can exert its inflammatory action is the gut: both GM and gut-associated lymphoid tissue (GALT) are influenced by LPS and shift towards an inflammatory pattern. The changes in GM and GALT induced by LPS are quite similar to the ones seen in IBD: GM loses diversity, while GALT T regulatory (Tregs) lymphocytes are reduced in number, with an increase in Th17 and Th1 lymphocytes. Additionally, the innate immune system is triggered, through the activation of toll-like receptor (TLR)-4, while the epithelium is directly damaged, further triggering inflammation. In this review, we will discuss the importance of the crosstalk between LPS, GM, and GALT, and discuss the possible implications.

The role of interleukin (IL)-6 in health and disease has been under a lot of scrutiny in recent years, particularly during the recent COVID-19 pandemic. The inflammatory pathways in which IL-6 is involved are also partly responsible of the development and progression of rheumatoid arthritis (RA), opening interesting perspectives in terms of therapy. Anti-IL-6 drugs are being used with variable degrees of success in other diseases and are being tested in RA. Results have been encouraging, particularly when anti-IL-6 has been used with other drugs, such as metothrexate (MTX). In this review we discuss the main immunologic aspects that make anti-IL-6 a good candidate in RA, but despite the main therapeutic options available to target IL-6, no gold standard treatment has been established so far.

The gut microbiota is central to the pathogenesis of several inflammatory and autoimmune diseases. While multiple mechanisms are involved, the immune system clearly plays a special role. Indeed, the breakdown of the physiological balance in gut microbial composition leads to dysbiosis, which is then able to enhance inflammation and to influence gene expression. At the same time, there is an intense cross-talk between the microbiota and the immunological niche in the intestinal mucosa. These interactions may pave the way to the development, growth and spreading of cancer, especially in the gastro-intestinal system. Here, we review the changes in microbiota composition, how they relate to the immunological imbalance, influencing the onset of different types of cancer and the impact of these mechanisms on the efficacy of traditional and upcoming cancer treatments.

How can the knowledge of probiotics and their mechanisms of action be translated into clinical practice when treating patients with diverticular disease and acute diverticulitis? Changes in microbiota composition have been observed in patients who were developing acute diverticulitis, with a reduction of taxa with anti-inflammatory activity, such as Clostridium cluster IV, Lactobacilli and Bacteroides. Recent observations supported that a dysbiosis characterised by decreased presence of anti-inflammatory bacterial species might be linked to mucosal inflammation, and a vicious cycle results from a mucosal inflammation driving dysbiosis at the same time. An alteration in gut microbiota can lead to an altered activation of nerve fibres, and subsequent neuronal and muscular dysfunction, thus favoring abdominal symptoms’ development. The possible role of dysbiosis and mucosal inflammation in leading to dysmotility is linked, in turn, to bacterial translocation from the lumen of the diverticulum to perivisceral area. There, a possible activation of Toll-like receptors has been described, with a subsequent inflammatory reaction at the level of the perivisceral tissues. Being aware that bacterial colonisation of diverticula is involved in the pathogenesis of acute diverticulitis, the rationale for the potential role of probiotics in the treatment of this disease becomes clearer. For this review, articles were identified using the electronic PubMed database through a comprehensive search conducted by combining key terms such as “gut microbiota”, “probiotics and gut disease”, “probiotics and acute diverticulitis”, “probiotics and diverticular disease”, “probiotics mechanism of action”. However, the amount of data present on this matter is not sufficient to draw robust conclusions on the efficacy of probiotics for symptoms’ management in diverticular disease.