There is increasing evidence suggesting a link between the autism spectrum disorder (ASD) and the gastrointestinal (GI) microbiome. Experimental and clinical studies have shown that patients diagnosed with ASD display alterations of the gut microbiota. These alterations do not only extend to the gut microbiota composition but also to the metabolites they produce, as a result of its connections with diet and the bidirectional interaction with the host. Thus, production of metabolites and neurotransmitters stimulate the immune system and influence the central nervous system (CNV) by stimulation of the vagal nerve, as an example of the gut-brain axis pathway. In this review we compose an overview of the interconnectivity of the different GI-related elements that have been associated with the development and severity of the ASD in patients and animal models. We review potential biomarkers to be used in future studies to unlock further connections and interventions in the treatment of ASD.

The glucosinolate‐myrosinase system in plants has been well studied over the years while relatively little research has been undertaken on the bacterial metabolism of glucosinolates. The products of myrosinase‐based glucosinolate hydrolysis in the human gut are important to health, particularly the isothiocyanates, as they are shown to have anticancer properties as well as other beneficial roles in human health. This review is concerned with the bacterial metabolism of glucosinolates but is not restricted to the human gut. Isothiocyanate production and nitrile formation are discussed together with the mechanisms of the formation of these compounds. Side chain modification of the methylsulfinylalkyl glucosinolates is reviewed and the implications for bioactivity of the resultant products are also discussed.

There is strong interest in using the gut microbiome for Parkinson’s disease (PD) diagnosis and treatment. However, a consensus on PD-associated microbiome features and a multi-study assessment of their diagnostic value is lacking. Here, we present a machine learning meta-analysis of PD microbiome studies of unprecedented scale (4489 samples). Within most studies, microbiome-based machine learning models accurately classify PD patients (average AUC 71.9%). However, these models are study-specific and do not generalise well across other studies (average AUC 61%). Training models on multiple datasets improves their generalizability (average LOSO AUC 68%) and disease specificity as assessed against microbiomes from other neurodegenerative diseases. Moreover, meta-analysis of shotgun metagenomes delineates PD-associated microbial pathways potentially contributing to gut health deterioration and favouring the translocation of pathogenic molecules along the gut-brain axis. Strikingly, microbial pathways for solvent and pesticide biotransformation are enriched in PD. These results align with epidemiological evidence that exposure to these molecules increases PD risk and raise the question of whether gut microbes modulate their toxicity. Here, we offer the most comprehensive overview to date about the PD gut microbiome and provide future reference for its diagnostic and functional potential.

The aim of this study was to establish continuous therapeutic-dose ampicillin (CTDA)-induced dysbiosis in a mouse model, mimicking typical adult exposure, with a view to using this to assess its impact on gut microbiota, intestinal metabolites and host immune responses. Mice were exposed to ampicillin for 14 days and antibiotic-induced dysbiosis was evaluated by alteration of microbiota and gut permeability. The cecal index was increased in the CTDA group, and the gut permeability indicated by fluorescent dextran, endotoxin and D-Lactate in the serum was significantly increased after antibiotic use. The tight-junction proteins ZO-1 and occludin in the colon were reduced to half the control level in CTDA. We found that alpha-diversity was significantly decreased in mice receiving CTDA, and microbial community structure was altered compared with the control. Key taxa were identified as CTDA-specific, and the relative abundance of Enterococcus and Klebsiella was particularly enriched while Lachnospiraceae, Coprobacillus and Dorea were depleted after antibiotic treatment. In particular, a significant increase in succinate and a reduction in butyrate was detected in CTDA mice, and the triggering of NF-κB enhancement reflected that the host immune response was influenced by ampicillin use. The observed perturbation of the microbiota was accompanied by modulation of inflammatory state; this included increase in interferon-γ and RegIIIγ, and a decrease in secretory IgA in the colon mucosa. This study allowed us to identify the key taxa associated with an ampicillin-induced state of dysbiosis in mice and to characterize the microbial communities via molecular profiling. Thus, this work describes the bacterial ecology of antibiotic exposure model in combination with host physiological characteristics at a detailed level of microbial taxa.

Aims This study evaluated the antibiotic-induced changes in microbial ecology, intestinal dysbiosis and low-grade inflammation; and the combined effect of four different Lactobacillus species on recovery of microbiota composition and improvement of gut barrier function in mice. Methods and Results Administration of the antibiotic ampicillin for 2 weeks decreased microbial community diversity, induced caecum tumefaction and increased gut permeability in mice. Application of a probiotic cocktail of four Lactobacillus species (JUP-Y4) modulated the microbiota community structure and promoted the abundance of potentially beneficial bacteria such as Akkermansia. Ampicillin administration led to a decline in Bacteroidetes from 46·6 ± 3·91% to 0·264 ± 0·0362%; the addition of JUP-Y4 restored this to 41·4 ± 2·87%. This probiotic supplementation was more effective than natural restoration, where the levels of Bacteroidetes were only restored to 29·3 ± 2·07%. Interestingly, JUP-Y4 treatment was more effective in the restoration of microbiota in faecal samples than in caecal samples. JUP-Y4 also significantly reduced the levels of d-lactate and endotoxin (lipopolysaccharide, LPS) in the serum of mice, and increased the expression of tight-junction proteins while reducing the production of inflammatory cytokines (TNF-α, IL-6, MCP-1, IFN-γ and IL-1β) in the ileum and the colon of antibiotic-treated mice. Conclusions JUP-Y4 not only promoted recovery from antibiotic-induced gut dysbiosis, but also enhanced the function of the gut barrier, reduced inflammation and lowered levels of circulating endotoxin in mice. Significance and Impact of the Study Consumption of a mixture of Lactobacillus species may encourage faster recovery from antibiotic-induced gut dysbiosis and gut microbiota-related immune disturbance.

Summary: Sulfate‐reducing bacteria (SRB) are widespread in human guts, yet their expansion has been linked to colonic diseases. We report the isolation, sequencing and physiological characterization of strain QI0027 ^T , a novel SRB species belonging to the class Desulfovibrionia . Metagenomic sequencing of stool samples from 45 Chinese individuals, and comparison with 1690 Desulfovibrionaceae metagenome‐assembled genomes recovered from humans of diverse geographic locations, revealed the presence of QI0027 ^T in 22 further individuals. QI0027 ^T encoded nitrogen fixation genes and based on the acetylene reduction assay, actively fixed nitrogen. Transcriptomics revealed that QI0027 ^T overexpressed 42 genes in nitrogen‐limiting conditions compared to cultures supplemented with ammonia, including genes encoding nitrogenases, a urea uptake system and the urease complex. Reanalyses of 835 public stool metatranscriptomes showed that nitrogenase genes from Desulfovibrio bacteria were expressed in six samples suggesting that nitrogen fixation might be active in the gut environment. Although frequently thought of as a nutrient‐rich environment, nitrogen fixation can occur in the human gut. Animals are often nitrogen limited and have evolved diverse strategies to capture biologically active nitrogen, ranging from amino acid transporters to stable associations with beneficial microbes that provide fixed nitrogen. QI0027 ^T is the first Desulfovibrio human isolate for which nitrogen fixation has been demonstrated, suggesting that some sulfate‐reducing bacteria could also play a role in the availability of nitrogen in the gut.