Novel Approach for Evaluation of Bacteroides fragilis Protective Role against Bartonella henselae Liver Damage in Immunocompromised Murine Model

Abstract

Bartonella henselae is a gram-negative facultative intracellular bacterium and is the causative agent of cat-scratch disease. Our previous data have established that Bacteroides fragilis colonization is able to prevent B. henselae damages through the polysaccharide A (PSA) in an experimental murine model. In order to determine whether the PSA is essential for the protection against pathogenic effects of B. henselae in immunocompromised hosts, SCID mice were co-infected with B. fragilis wild type or its mutant B. fragilis ΔPSA and the effects of infection on murine tissues have been observed by High-Frequency Ultrasound (HFUS), histopathological examination, and Transmission Electron Microscopy (TEM). For the first time, echostructure, hepatic lobes length, vascular alterations, and indirect signs of hepatic dysfunctions, routinely used as signs of disease in humans, have been analyzed in an immunocompromised murine model. Our findings showed echostructural alterations in all infected mice compared with the Phosphate Buffer Solution (PBS) control group; further, those infected with B. henselae and co-infected with B. henselae/B. fragilis ΔPSA presented the major echostructural alterations. Half of the mice infected with B. henselae and all those co-infected with B. henselae/B. fragilis ΔPSA have showed an altered hepatic echogenicity compared with the renal cortex. The echogenicity score of co-infected mice with B. henselae/B. fragilis ΔPSA differed significantly compared with the PBS control group (p < 0.05). Moreover the inflammation score of the histopathological evaluation was fairly concordant with ultrasound findings. Ultrastructural analysis performed by TEM revealed no significant alterations in liver samples of SCID mice infected with B. fragilis wild type while those infected with B. fragilis ΔPSA showed the presence of collagen around the main vessels compared with the PBS control group. The liver samples of mice infected with B. henselae showed macro-areas rich in collagen, stellate cells, and histiocytic cells. Interestingly, our data demonstrated that immunocompromised SCID mice infected with B. henselae and co-infected with B. henselae/B. fragilis ΔPSA showed the most severe morpho-structural liver damage. In addition, these results suggests that the HFUS together with histopathological evaluation could be considered good imaging approach to evaluate hepatic alterations.

Finding a needle in a haystack: Bacteroides fragilis polysaccharide A as the archetypical symbiosis factor

“…In a coinfection experiment, WT B. fragilis , but not the ΔPSA mutant, prevented uptake of B. henselae by endothelial progenitor cells. Furthermore, WT B. fragilis prevented B. henselae –induced tissue damage in a mouse model of coinfection, while the ΔPSA mutant failed to do so …”

“…Although B. fragilis can contribute to intra‐abdominal abscess formation, soft tissue infections, and bacteremia when present outside the gut, it has many beneficial effects when contained within the gut—that is, in its normal habitat. Monocolonization of previously germ‐free mice with B. fragilis can correct cellular and developmental defects in the immune system, prevent intestinal inflammation in animal models of colitis, protect against infections, and even modulate immune responses in extraintestinal tisues …”

Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases

“…It has been observed that this bacterium plays a beneficial role in patients that suffer from IBD (Morgan and Harris, 2015 ). There is evidence that Bacteroides can be beneficial for maintaining the homeostasis in models of intra-abdominal sepsis and experimental colitis (Tzianabos et al, 1995 ; Pagliuca et al, 2016 ). This seems to be the case for B. fragilis , as its polysaccharide (PSA) induces IL-10 secretion by Tregs (Ochoa-Reparaz et al, 2010 ).…”

Kang‐Xian Pills Inhibit Inflammatory Response and Decrease Gut Permeability to Treat Carbon Tetrachloride‐Induced Chronic Hepatic Injury through Modulating Gut Microbiota

“…Bacteroides has been shown to produce many metabolites, such as short-chain fatty acids (SCFAs) [ 34 ] and polysaccharide A (PSA) [ 35 ]. Studies have shown that Bacteroides fragilis could protect against Bartonella henselae -induced liver damage through producing PSA [ 36 ]. SCFAs are derived from indigestible carbohydrates by the fermentation of gut microbiota and include compounds such as butyrate, propionate, and acetate [ 37 ].…”