Mycobacterium avium Subspecies paratuberculosis Infection Modifies Gut Microbiota under Different Dietary Conditions in a Rabbit Model

Abstract

Mycobacterium avium subspecies paratuberculosis (MAP) the causative agent of paratuberculosis, produces a chronic granulomatous inflammation of the gastrointestinal tract of ruminants. It has been recently suggested that MAP infection may be associated with dysbiosis of intestinal microbiota in ruminants. Since diet is one of the key factors affecting the balance of microbial populations in the digestive tract, we intended to evaluate the effect of MAP infection in a rabbit model fed a regular or high fiber diet during challenge. The composition of microbiota of the cecal content and the sacculus rotundus was studied in 20 New Zealand white female rabbits. The extracted DNA was subjected to paired-end Illumina sequencing of the V3-V4 hypervariable region of the 16S rRNA gene for microbiota analysis. Microbial richness (Chao1) in the cecal content was significantly increased by MAP infection in regular diet rabbits (p = 0.0043) and marginally increased (p = 0.0503) in the high fiber group. Analysis of beta-diversity showed that MAP infection produces deeper changes in the microbiota of sacculus rotundus than in the cecal content. A lower abundance of Proteobacteria in the cecal content of infected animals fed the high fiber diet and also lower abundance of Bacteroidetes in the sacculus rotundus of infected animals fed the regular diet were observed. Based on OPLS-DA analysis, we observed that some bacteria repeatedly appear to be positively associated with infection in different samples under different diets (families Dehalobacteriaceae, Coriobacteriaceae, and Mogibacteriaceae; genus Anaerofustis). The same phenomenon was observed with some of the bacteria negatively associated with MAP infection (genera Anaerostipes and Coprobacillus). However, other groups of bacteria (Enterobacteriaceae family and ML615J-28 order) were positively associated with infection in some circumstances and negatively associated with infection in others. Data demonstrate that MAP infection and diet changes do interact and result in shifts in the microbiota of the cecal content and sacculus rotundus of rabbits.

Rabbit Microbiota Changes Throughout the Intestinal Tract

“…Little is known about the presence of Anaerofustis (family Eubacteriaceae ) in intestinal communities. Arrazuria et al (2016) found an association between the presence of this genus in cecal samples collected from female rabbits and Mycobacterium avium paratuberculosis infection. Some Anaerofustis species could be involved in the fermentation of carbohydrates and glucose metabolism in the cecum ( Lawson, 2015 ), which could be compatible with the overrepresentation we observed for this genus in cecum which is well known to be the main fermenting organ in rabbits.…”

Bifidobacterium pseudocatenulatum LI09 and Bifidobacterium catenulatum LI10 attenuate D-galactosamine-induced liver injury by modifying the gut microbiota

“…A decline of Coprococcus has been demonstrated in patients with intestinal 32 , 33 , neuropsychological 34 , 35 , infectious 36 , and atopic diseases 37 , as well as liver diseases 38 – 40 . A depletion of Dorea has been found in patients with intestinal 41 and infectious diseases 36 , along with liver disease 42 , and a suppression of Anaerostipes has been shown in patients with paratuberculosis infection 43 . In addition, genus Clostridium XI , a SCFA-producing microorganism, within the family Peptostreptococcaceae , was also found to be significantly depleted in the PC group.…”

Profound remission in Crohn’s disease requiring no further treatment for 3–23 years: a case series

“…Genetic factors, such as the NOD2CARD15 mutations contributes to risk of developing disease, as these enable the pathogenesis of CD and also have been shown to confer an increased risk to mycobacterial infections [33,34]. MAP itself can further disrupt the biodiversity of the microbial environment of the gut [35], leading to excessive and maladaptive immune responses, which current immune suppressive therapy target. MAP behaviour is similar to other mycobacteria, where there are high infectivity rates but low expression/pathogenicity.…”

“…The ability for MAP to influence the gut microbiome has been demonstrated in animal rabbit [35] and cattle [42] models. We propose that the inability to clear MAP from the macrophage and the resulting dysbiosis from viable mycobacteria, leads to granulomas and the relapsing, remitting behaviour observed in CD.…”