Salmonella Strain Specificity Determines Post-typhoid Central Nervous System Complications: Intervention by Lactiplantibacillus plantarum at Gut-Brain Axis

Abstract

Neurological complications occurring due to Salmonella infection in some typhoid patients remain a relatively unexplored serious complication. This study firstly aimed to explore whether disseminative ability of Salmonella from gut to brain is strain specific or not and on the basis of bacterial load, histopathology, and behavioral changes, it was observed that Salmonella enterica serovar Typhimurium NCTC 74 did not cause brain infection in murine model in contrast to Salmonella Typhimurium SL1344. Simultaneously, alarming escalation in antimicrobial resistance, making the existing antibiotics treatment inefficacious, prompted us to evaluate other bio-compatible strategies as a potential treatment option. In this context, the role of gut microbiota in influencing behavior, brain neurochemistry, and physiology by modulating key molecules associated with gut-brain axis has captured the interest of the scientific community. Followed by in vitro screening of potential probiotic strains for beneficial attributes, efficacy of the selected strain was systematically evaluated at various levels of gut-brain axis against Salmonella induced brain infection. Analysis of behavioral (depression, anxiety, and locomotor), neurochemical [gamma amino butyric acid and acetylcholinesterase (AChE)], neuropathological (brain and intestinal histology; bacterial burden), and immunohistochemical studies (tight junction proteins expression) revealed its role in preventing serious manifestations and proving its potential as "psychobiotic." To the best of our knowledge, this is the first report elaborating strain specificity of Salmonella in causing post-typhoidal neurological manifestations and simultaneous use of probiotic in managing the same by influencing the pathophysiology at gut-brain axis.

Diet, Gut Microbiota and COVID-19

“…Probiotics have been reported to restore this balance and act as 'psychobiotics', thereby serving as an alternate treatment option. In this context, we recently studied the effect of a potential probiotic strain, Lactiplantibacillus plantarum (RTA 8), on psychological, histological and physiological status of diseased host and its role in ameliorating host health by modulating various aspects of the gut-brain axis [57]. The schematic representation of the possible association as mentioned above has been shown in Fig.…”

Clostridium butyricum Induces the Production and Glycosylation of Mucins in HT-29 Cells

“…Human gastrointestinal tract (GIT) is inhabited by trillions of bacteria with more than 1000 identified species, with a density of 10 11 bacterial cells per gram wet weight in the colon contents (Rehman et al, 2011;Parker et al, 2020). These intestinal bacteria involve in many critical physiological functions related to host health (Kaur et al, 2020;Reyes et al, 2020;Xu et al, 2020). In healthy individuals, the composition of intestinal microbiota usually remains in constant equilibrium for a long period of time (Guo et al, 2020;Leon-Coria et al, 2020).…”

Bi-directional elucidation of Lactiplantibacillus plantarum (RTA 8) intervention on the pathophysiology of gut-brain axis during Salmonella brain infection

“…In contrast to the previously conducted independent study [ 15 ], herein, exclusively the prophylactic potential of L. plantarum (RTA 8) in combating Salmonella induced brain infection was evaluated. It was inferred that decreasing the duration of L. plantarum (RTA 8) administration from 14 to only 7 days prior to infection, did not affect its efficacy in preventing brain infection.…”

“…Reduction in luminal pH due to production of short chain fatty acids by L. plantarum (RTA 8) along with production of IgA and other potent antimicrobial substances might have resulted in clearance of Salmonella [ 18 , 19 ]. Additionally, the abilities of probiotics in occupying receptor binding sites at the epithelial surface, strengthening the intestinal microstructure and increasing the villus length, might have further blocked pathogen adherence [ 15 , 20 , 21 ]. All these factors might have conferred colonization resistance to the host against such deadly pathogens, thereby preventing their translocation to other organs such as the brain.…”

“…Additionally, the capability of these bacteria to function as psychobiotics by improving the psychological status along with their impact on the host pathology and physiology has opened diverse areas of targeted therapy which might prove useful in a variety of related manifestations [ 14 ]. In our previous study, administration of Lactiplantibacillus plantarum (RTA 8) was found to be useful in ameliorating Salmonella induced brain infection in mouse model [ 15 ]. To the best of our awareness, this is the first study elaborating on the prophylactic effect of L. plantarum (RTA 8) in modulating the amount of neurotransmitters and other neuroactive molecules such as BDNF along with mucin genes, at the gut-brain axis, thereby preventing Salmonella induced neurological manifestations.…”