Viral dysbiosis in children with new-onset celiac disease

Viruses are common components of the intestinal microbiome, modulating host bacterial metabolism and interacting with the immune system, with a possible role in the pathogenesis of immune-mediated diseases such as celiac disease (CeD). The objective of this study was to characterize the virome profile in children with new-onset CeD. We used metagenomic analysis of viral DNA in mucosal and fecal samples from children with CeD and controls and performed sequencing using the Nextera XT library preparation kit. Abundance log2 fold changes were calculated using differential expression and linear discriminant effect size. Shannon alpha and Bray–Curtis beta diversity were determined. A total of 40 children with CeD and 39 controls were included. We found viral dysbiosis in both fecal and mucosal samples. Examples of significantly more abundant species in fecal samples of children with CeD included Human polyomavirus 2, Enterobacteria phage mEpX1, and Enterobacteria phage mEpX2; whereas less abundant species included Lactococcus phages ul36 and Streptococcus phage Abc2. In mucosal samples however, no species were significantly associated with CeD. Shannon alpha diversity was not significantly different between CeD and non-CeD groups and Bray–Curtis beta diversity showed no significant separation between CeD and non-CeD samples in either mucosal or stool samples, whereas separation was clear in all samples. We identified significant viral dysbiosis in children with CeD, suggesting a potential role in the pathogenesis of CeD indicating the need for further studies.

Oral Administration of Nanopeptide CMCS-20H Conspicuously Boosts Immunity and Precautionary Effect Against Bacterial Infection in Fish

Massive mortalities caused by bacterial infections in intensive aquaculture result in serious economic losses. In this study, a novel antimicrobial peptide gcIFN-20H was efficiently expressed in Pichia pastoris (GS115) and loaded on carboxylmethyl chitosan (CMCS) to prepare CMCS-20H nanoparticles. Through physical characterization assays (TEM, DLS, BCA, and Raman) and biological activity tests (antimicrobial activity and cytotoxicity), CMCS-20H nanopeptide was verified to be spherical nanoparticles with sustained release, antimicrobial activity, and negligible toxicity. CMCS-20H nanoparticles are more resistant to intestinal degradation than unloaded gcIFN-20H by indirect immunofluorescence assay. Oral administration was then carried out for 42 days. Complement C3 content, lysozyme, and total superoxide dismutase activities are highest in CMCS-20H group by serum biochemistry index assays. After challenge with Aeromonas hydrophila, the survival rate in CMCS-20H group is highest (46%), which is 64% higher than the control group (28%). Meanwhile, the tissue bacterial loads (intestine, spleen, head kidney, trunk kidney, hepatopancreas, muscle, and blood) in the CMCS-20H group are significantly lower than other groups. By PAS staining analysis, the number of intestinal villi goblet cells and the thickness of mucin in the CMCS-20H group obviously increased. CMCS-20H effectively enhances mRNA expressions of some important immune genes (IL-1β, IL-6, TNF-α, IL-2, IFN-γ2, and IgM). The minimal tissue lesions (Intestine, spleen, and trunk kidney) were seen in the CMCS-20H group by histopathological examination. 16S rRNA sequencing showed that oral CMCS-20H maintains the intestinal microbiome homeostasis in bacterial infection. The results indicate that the novel nanopeptide CMCS-20H as the immunopotentiator can remarkably boost fish immunity and precautionary effect by oral administration and address the theoretical mechanisms and insights into the promising application prospect in aquaculture.

Antibiotics in early life and childhood pre-B-ALL. Reasons to analyze a possible new piece in the puzzle

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer with precursor B-cell ALL (pB-ALL) accounting for ~ 85% of the cases. Childhood pB-ALL development is influenced by genetic susceptibility and host immune responses. The role of the intestinal microbiome in leukemogenesis is gaining increasing attention since Vicente-Dueñas’ seminal work demonstrated that the gut microbiome is distinct in mice genetically predisposed to ALL and that the alteration of this microbiome by antibiotics is able to trigger pB-ALL in Pax5 heterozygous mice in the absence of infectious stimuli. In this review we provide an overview on novel insights on the role of the microbiome in normal and preleukemic hematopoiesis, inflammation, the effect of dysbiosis on hematopoietic stem cells and the emerging importance of the innate immune responses in the conversion from preleukemic to leukemic state in childhood ALL. Since antibiotics, which represent one of the most widely used medical interventions, alter the gut microbial composition and can cause a state of dysbiosis, this raises exciting epidemiological questions regarding the implications for antibiotic use in early life, especially in infants with a a preleukemic “first hit”. Sheading light through a rigorous study on this piece of the puzzle may have broad implications for clinical practice.

The Potential Prebiotic Berberine Combined With Methimazole Improved the Therapeutic Effect of Graves’ Disease Patients Through Regulating the Intestinal Microbiome

Graves’ disease, a typical metabolism disorder, causes diffuse goiter accompanied by ocular abnormalities and ocular dysfunction. Although methimazole (MI) is a commonly used drug for the treatment of GD, the efficacy of methimazole is only limited to the control of clinical indicators, and the side effects of MI should be seriously considered. Here, we designed a 6-month clinical trial that divided the patients into two groups: a methimazole group (n=8) and a methimazole combined with potential prebiotic berberine group (n=10). The effects of both treatments on thyroid function and treatment outcomes in patients with GD were assessed by thyroid index measurements and gut microbiota metagenomic sequencing. The results showed that the addition of berberine restored the patients’ TSH and FT3 indices to normal levels, whereas MI alone restored only FT3. In addition, TRAb was closer to the healthy threshold at the end of treatment with the drug combination. MI alone failed to modulate the gut microbiota of the patients. However, the combination of berberine with methimazole significantly altered the microbiota structure of the patients, increasing the abundance of the beneficial bacteria Lactococcus lactis while decreasing the abundance of the pathogenic bacteria Enterobacter hormaechei and Chryseobacterium indologenes. Furthermore, further mechanistic exploration showed that the addition of berberine resulted in a significant upregulation of the synthesis of enterobactin, which may have increased iron functioning and thus restored thyroid function. In conclusion, methimazole combined with berberine has better efficacy in patients with GD, suggesting the potential benefit of berberine combined with methimazole in modulating the composition of intestinal microbes in the treatment of GD, providing new strong evidence for the effectiveness of combining Chinese and Western drugs from the perspective of modulating the intestinal microbiota.

Age and injury size influence the magnitude of fecal dysbiosis in adult burn patients

Clinical studies have demonstrated that age ≥ 50 years old is an independent risk factor associated with poor prognosis after burn injury, the second leading cause of traumatic injuries in the aged population. While mechanisms driving age-dependent post-burn mortality are perplexing, changes in the intestinal microbiome however may contribute to the heightened, dysregulated systemic response seen in aging burn patients. The fecal microbiome from 22 patients admitted to a verified burn center from July 2018 to February 2019 were stratified based on age of 50 years and total burn surface area (TBSA) size of ≥10%. Significant differences (P = 0.014) in overall microbiota community composition (i.e., beta diversity) were measured across the four patient groups, young <10% TBSA, young ≥10% TBSA, older <10% TBSA, and older ≥10% TBSA. Differences in beta diversity were driven by %TBSA (P = 0.013) and trended with age (P = 0.087). Alpha diversity components, richness, evenness, and Shannon diversity were measured. We observed significant differences in bacterial species evenness (P = 0.0023) and Shannon diversity (P = 0.0033) between the groups. There were significant correlations between individual bacterial species and levels of SCFA. Specifically, levels of fecal butyrate correlated with the presence of Enterobacteriaceae, an opportunistic gut pathogen, when elevated in burn patients lead to worsen outcomes. Overall, our findings reveal that age-specific changes in the fecal microbiome following burn injuries may contribute to immune system dysregulation in patients with varying TBSA burns and potentially lead to worsen clinical outcomes with heightened morbidity and mortality.

The Technological Advance and Application of Coprolite Analysis

Coprolites (mummified or fossilized feces), belonging to the group of ichnofossils, are fossilized remains of feces produced by animals. Various types of data from coprolites provide detailed evidence of the producer’s condition, like diet, intestinal microbiome, virus infection and parasites diseases. In addition, the palaeoenvironment information relevant to producers’ ecological niche can be drawn from taphonomy details the coprolites mirrored. At present, the phylogenetic clues of the producer’s population can be determined by advanced molecular biotechnologies. With the integration of multiple methods and techniques, coprolite has been widely accepted as an ideal material to study the diet, evolution, and palaeoenvironment of producers. In this paper, we reviewed the history of coprolite research, enumerated and interpreted the data recovered from coprolites, and explained their research value to palaeocoprology and evolutionary biology. Finally, we summarized the current directions of coprolite research and looked into its future prospects.

Gut dysbiosis is associated with acceleration of lupus nephritis

The gut microbiota (GM) exerts a strong influence over the host immune system and dysbiosis of this microbial community can affect the clinical phenotype in chronic inflammatory conditions. To explore the role of the GM in lupus nephritis, we colonized NZM2410 mice with Segmented Filamentous Bacteria (SFB). Gut colonization with SFB was associated with worsening glomerulonephritis, glomerular and tubular immune complex deposition and interstitial inflammation compared to NZM2410 mice free of SFB. With SFB colonization mice experienced an increase in small intestinal lamina propria Th17 cells and group 3 innate lymphoid cells (ILC3s). However, although serum IL-17A expression was elevated in these mice, Th17 cells and ILC3s were not detected in the inflammatory infiltrate in the kidney. In contrast, serum and kidney tissue expression of the macrophage chemoattractants MCP-1 and CXCL1 were significantly elevated in SFB colonized mice. Furthermore, kidney infiltrating F4/80+CD206+M2-like macrophages were significantly increased in these mice. Evidence of increased gut permeability or “leakiness” was also detected in SFB colonized mice. Finally, the intestinal microbiome of SFB colonized mice at 15 and 30 weeks of age exhibited dysbiosis when compared to uncolonized mice at the same time points. Both microbial relative abundance as well as biodiversity of colonized mice was found to be altered. Collectively, SFB gut colonization in the NZM2410 mouse exacerbates kidney disease, promotes kidney M2-like macrophage infiltration and overall intestinal microbiota dysbiosis.

Intestinal Bacteroides Modulates Systemic Inflammation and the Microbial Ecology in a Mouse Model of CF: Evidence for Propionate and other Short Chain Fatty Acids Reducing Systemic Inflammatory Cytokines

Persons with cystic fibrosis, starting in early life, have intestinal microbiome dysbiosis characterized in part by a decreased relative abundance of the genus Bacteroides. Bacteroides is a major producer of the intestinal short chain fatty acid (SCFA) propionate. We demonstrate here that CFTR-/- Caco-2 intestinal epithelial cells are responsive to the anti-inflammatory effects of propionate. Furthermore, Bacteroides isolates inhibit the IL-1β-induced inflammatory response of CFTR-/- Caco-2 intestinal epithelial cells and do so in a propionate-dependent manner. Bacteroides isolates also produce low levels of butyrate; this SCFA is positively correlated with inhibition of the inflammatory response. Finally, the introduction of Bacteroides-supplemented stool from infants with CF into the gut of CftrF508del mice results in an increase in propionate in the stool as well as the reduction in several systemic pro-inflammatory cytokines. Bacteroides supplementation also reduced the fecal relative abundance of E. coli, indicating a potential interaction between these two microbes, consistent with previous clinical studies. Together, our data indicate the important role of Bacteroides and Bacteroides-derived propionate in the context of the developing microbiome in infants and children with CF, which could help explain the observed gut-lung axis in CF.

The small bowel microbiome changes significantly with age and aspects of the ageing process

Gut microbiome changes have been associated with human ageing and implicated in age-related diseases including Alzheimer’s disease and Parkinson’s disease. However, studies to date have used stool samples, which do not represent the entire gut. Although more challenging to access, the small intestine plays critical roles in host metabolism and immune function. In this paper (Leite et al. (2021), Cell Reports, doi: 10.1016/j.celrep.2021.109765), we demonstrate significant differences in the small intestinal microbiome in older subjects, using duodenal aspirates from 251 subjects aged 18-80 years. Differences included significantly decreased microbial diversity in older subjects, driven by increased relative abundance of phylum Proteobacteria, particularly family Enterobacteriaceae and coliform genera Escherichia and Klebsiella. Moreover, while this decreased diversity was associated with the ‘ageing process’ (comprising chronologic age, number of medications, and number of concomitant diseases), changes in certain taxa were found to be associated with number of medications alone (Klebsiella), number of diseases alone (Clostridium, Bilophila), or chronologic age alone (Escherichia, Lactobacillus, Enterococcus). Lastly, many taxa associated with increasing chronologic age were anaerobes. These changes may contribute to changes in human health that occur during the ageing process.