Could Candida Overgrowth Be Involved in the Pathophysiology of Autism?

The purpose of this review is to summarize the current acquiredknowledge of Candida overgrowth in the intestine as a possible etiology of autism spectrum disorder (ASD). The influence of Candida sp. on the immune system, brain, and behavior of children with ASD isdescribed. The benefits of interventions such as a carbohydrates-exclusion diet, probiotic supplementation, antifungal agents, fecal microbiota transplantation (FMT), and microbiota transfer therapy (MTT) will be also discussed. Our literature query showed that the results of most studies do not fully support the hypothesis that Candida overgrowth is correlated with gastrointestinal (GI) problems and contributes to autism behavioral symptoms occurrence. On the one hand, it was reported that the modulation of microbiota composition in the gut may decrease Candida overgrowth, help reduce GI problems and autism symptoms. On the other hand, studies on humans suggesting the beneficial effects of a sugar-free diet, probiotic supplementation, FMT and MTT treatment in ASD are limited and inconclusive. Due to the increasing prevalence of ASD, studies on the etiology of this disorder are extremely needed and valuable. However, to elucidate the possible involvement of Candida in the pathophysiology of ASD, more reliable and well-designed research is certainly required.

Clostridioides difficile-Infection (CDI)

Clostridioides difficile is a Gram positive, spore-forming bacillus colonizing the lower gastrointestinal tract. Use of antibiotics, older age, and underlying diseases contribute to changes in the microbial flora of the gut, which may lead to the production of toxins that cause C. difficile infection (CDI), with symptoms ranging from mild to moderate diarrhea to severe diarrhea, pseudomembranous colitis, toxic megacolon and sepsis. CDI is difficult to treat and has a high risk of recurrence. The fecal-oral route is the predominant mode of C. difficile transmission. The highest CDI incidence rates are reported from developed countries, particularly the United States, but limited disease awareness and surveillance capacity may lead to underestimation of disease burden elsewhere. Treatment consists of stopping ongoing antibiotic treatment, specific anti-CDI antibiotics and fecal microbiota transplant (FMT). CDI recurrence can be prevented by an anti-toxin B monoclonal antibody, bezlotoxumab. Various hygiene measures should be applied but they are costly and of variable effect. A candidate vaccine directed at the C. difficile toxin failed in the past, possibly due to a change in the epitope through inactivation or to a suboptimal immunization schedule. Currently, only one vaccine candidate based on genetically and chemically detoxified toxins A and B is in phase III studies.

Prebiotic Galacto-Oligosaccharides Impact Stool Frequency and Fecal Microbiota in Self-Reported Constipated Adults: A Randomized Clinical Trial

Constipation is a major issue for 10–20% of the global population. In a double-blind randomized placebo-controlled clinical trial, we aimed to determine a dose-response effect of galacto-oligosaccharides (GOS) on stool characteristics and fecal microbiota in 132 adults with self-reported constipation according to Rome IV criteria (including less than three bowel movements per week). Subjects (94% females, aged: 18–59 years) received either 11 g or 5.5 g of BiotisTM GOS, or a control product, once daily for three weeks. Validated questionnaires were conducted weekly to study primarily stool frequency and secondary stool consistency. At base- and endline, stool samples were taken to study fecal microbiota. A trend towards an increased stool frequency was observed after the intervention with 11 g of GOS compared to control. While during screening everybody was considered constipated, not all subjects (n = 78) had less than three bowel movements per week at baseline. In total, 11 g of GOS increased stool frequency compared to control in subjects with a low stool frequency at baseline (≤3 bowel movements per week) and in self-reported constipated adults 35 years of age or older. A clear dose-response of GOS was seen on fecal Bifidobacterium, and 11 g of GOS significantly increased Anaerostipes hadrus. In conclusion, GOS seems to be a solution to benefit adults with a low stool frequency and middle-aged adults with self-reported constipation.

Sources of Dietary Fiber Affect the SCFA Production and Absorption in the Hindgut of Growing Pigs

Effects of different dietary fiber (DF) sources on short-chain fatty acids (SCFA) production and absorption in the hindgut of growing pigs were studied by an in vivo–vitro (ileal cannulated pigs and fecal inoculum-based fermentation) method. Thirty-six cannulated pigs (body weight: 48.5 ± 2.1 kg) were randomly allocated to 6 treatments containing the same DF content (16.5%), with either wheat bran (WB), corn bran (CB), sugar beet pulp (SBP), oat bran (OB), soybean hulls (SH), or rice bran (RB) as DF sources. Pigs were allowed 15 days for diet adaptation, and then, fresh ileal digesta and feces were collected to determine SCFA concentration which was normalized for food dry matter intake (DMI) and the hindgut DF fermentability. Fecal microbiota was inoculated into the freeze-dried ileal digesta samples to predict the ability of SCFA production and absorption in the hindgut by in vitro fermentation. The SH group had the largest concentration of total SCFA and propionate in ileal digesta and fecal samples of growing pigs (p < 0.05). Nonetheless, the predicted acetate, total SCFA production, absorption in the SBP group were the highest (p < 0.01), but the lowest in the OB group (p < 0.01) among all groups. Even SBP and OB group had a similar ratio of soluble DF (SDF) to insoluble DF (IDF). The CB group had high determined ileal and fecal butyrate concentration but the lowest butyrate production and absorption in the hindgut (p < 0.01). Overall, the source of DF had a great impact on the hindgut SCFA production and absorption, and SBP fiber had a great potential to increase hindgut SCFA production and absorption.

Binary toxin expression by Clostridioides difficile is associated with worse disease

Background The incidence of Clostridioides difficile infection (CDI) has increased over the past two decades and is considered an urgent threat by the Centers for Disease Control. Hypervirulent strains such as ribotype 027, that possess genes for the additional toxin C. difficile binary toxin (CDT), are contributing to increased morbidity and mortality. Methods We retrospectively tested stool from 215 CDI patients for CDT by enzyme-linked immunosorbent assay (ELISA). Stratifying patients by CDT status, we assessed if disease severity and clinical outcomes correlated with CDT positivity. Additionally, we completed qPCR DNA extracted from patient stool to detect cdtB gene. Lastly, we performed 16 S rRNA gene sequencing to examine if CDT positive samples had an altered fecal microbiota. Results We found that patients with CdtB, the pore forming component of CDT, detected in their stool by ELISA were more likely to have severe disease with a higher 90-day mortality. CDT positive patients also had higher C. difficile bacterial burden and white blood cell counts. There was no significant difference in gut microbiome diversity between CDT positive and negative patients. Conclusions Patients with fecal samples that were positive for CDT had increased disease severity and worse clinical outcomes. Utilization of PCR and C. difficile Toxins A and B testing may not reveal the entire picture when diagnosing CDI, with the detection of CDT-expressing strains valuable in identifying patients at risk of more severe disease.

Fecal microbiota and diet compositions of muskox female adults and calves

Gut microbiome is vertically transmitted by maternal lactation at birth in mammals. In this study, we investigated the gut microbiome and diet compositions of muskox, a large herbivore in the high Arctic. From muskox feces in Ella Island, East Greenland, we compared the microbiota composition using bacterial 16S rRNA gene sequencing and the dietary compositions of six female adults and four calves have been compared. Firmicutes was the most abundant bacterial phylum in both adults and calves, comprising 94.36% and 94.03%, respectively. There were significant differences in the relative abundance of two Firmicutes families: the adults were mainly dominated by Ruminococcaceae (73.90%), while the calves were dominated by both Ruminococcaceae (56.25%) and Lachnospiraceae (24.00%). Stable isotope analysis on the feces and eight referential plant samples in the study area showed that both adults and calves had similar ranges of 13C and 15N, possibly derived from the dominant diet plants of Empetrum nigrum and Salix glauca. Despite the similar diets, the different gut microbiome compositions in muskox adults and calves indicate that the gut microbiome of the calves may not be fully colonized yet as much as the one of the adults.