Clostridium difficile-related postinfectious IBS: a case of enteroglial microbiological stalking and/or the solution of a conundrum?

Abstract

Post-infectious irritable bowel syndrome is a well-defined pathological entity that develops in about one-third of subjects after an acute infection (bacterial, viral) or parasitic infestation. Only recently it has been documented that an high incidence of post-infectious irritable bowel syndrome occurs after Clostridium difficile infection. However, until now it is not known why in some patients recovered from this infection the gastrointestinal disturbances persist for months or years. Based on our in vitro studies on enteric glial cells exposed to the effects of C. difficile toxin B, we hypothesize that persistence of symptoms up to the development of irritable bowel syndrome might be due to a disturbance/impairment of the correct functions of the enteroglial intestinal network.

Dysbiosis-Associated Enteric Glial Cell Immune-Activation and Redox Imbalance Modulate Tight Junction Protein Expression in Gulf War Illness Pathology

“…This ultimately may result in programmed cell death in glia by pyroptosis or apoptosis as shown elsewhere (Macchioni et al, 2017). The general loss in enteric glia could lead to suboptimal functioning of enteric neurons and even enteric neuropathy (Bassotti et al, 2018). This mechanism could be a possible explanation for the symptoms of GWI which continue to persist for 25 years though the present report does not study the role of an activated EGC on intestinal neurons.…”

Increasing Evidence That Irritable Bowel Syndrome and Functional Gastrointestinal Disorders Have a Microbial Pathogenesis

“…The elevated breath methane production in these individuals could alternatively reflect the outgrowth of "slow-growing" microbes, which are advantaged in conditions of slowed colonic transit and are resistant to the lack of water that characterize firmer stool (Quigley and Spiller, 2016). However, another study did not observe an association between breath methane production and constipation or colonic transit, although they FIGURE 2 | In subjects with post-infectious IBS, the infection by certain pathogens, such as Clostridium difficile (Wadhwa et al, 2016;Bassotti et al, 2018), Salmonella (McKendrick and Read, 1994), Shigella (Gwee et al, 1999;Wang et al, 2004) or Escherichia coli (Marshall et al, 2006) compromises the integrity of the epithelial barrier, triggers inflammation and decreases microbial diversity and beneficial bacteria, detrimentally affecting GI microbiota composition (Jalanka-Tuovinen et al, 2014). The microbiota composition in post-infectious IBS subjects differs from both IBS subjects and healthy controls, featuring an increase in Bacteroidetes, which are usually decreased in general IBS, and a decrease in Firmicutes, including Clostridium clusters III, IV and XIVa (Sundin et al, 2014).…”

“… In subjects with post-infectious IBS, the infection by certain pathogens, such as Clostridium difficile (Wadhwa et al, 2016 ; Bassotti et al, 2018 ), Salmonella (McKendrick and Read, 1994 ), Shigella (Gwee et al, 1999 ; Wang et al, 2004 ) or Escherichia coli (Marshall et al, 2006 ) compromises the integrity of the epithelial barrier, triggers inflammation and decreases microbial diversity and beneficial bacteria, detrimentally affecting GI microbiota composition (Jalanka-Tuovinen et al, 2014 ). The microbiota composition in post-infectious IBS subjects differs from both IBS subjects and healthy controls, featuring an increase in Bacteroidetes, which are usually decreased in general IBS, and a decrease in Firmicutes, including Clostridium clusters III, IV and XIVa (Sundin et al, 2014 ).…”

The possible role of bacteria, viruses, and parasites in initiation and exacerbation of irritable bowel syndrome

“…Moreover, 4-12% of patients might have PI-IBS symptoms after CDI (Gutiérrez et al, 2015;Wadhwa et al, 2016). C. difficile primarily affects the colon and can produce toxins of types A and B (TcdA and TcdB; Clayton et al, 2012;Piche et al, 2007;Wadhwa et al, 2016), which harmfully influence enteric cell populations, such as enterocytes, colonocytes, and enteric neurons (Bassotti et al, 2018;Pruitt & Lacy, 2012). Using its toxins, C.…”

“…difficile may behave like a microbiological stalker with regard to the intestinal enteric glial cells (EGC) network that can be disorganized and/ or disrupted based on the exposure level of these toxins to the gut (Bassotti et al, 2018). Due to the significance of EGC function for suitable gut homeostasis, clinical consequences can be different with respect to the intensity and duration of exposure to the toxins (Bassotti et al, 2018;Longstreth, Chen, Wong, & Yao, 2017;Wadhwa et al, 2016).…”