The vaginal microbiota plays a significant role in health and disease of the female reproductive tract. Next-generation sequencing techniques based upon the analysis of bacterial 16S rRNA genes ...permit in-depth study of vaginal microbial community structure to a level of detail not possible with standard culture-based microbiological techniques. The human papillomavirus (HPV) causes both cervical intraepithelial neoplasia (CIN) and cervical cancer. Although the virus is highly prevalent, only a small number of women have a persistent HPV infection and subsequently develop clinically significant disease. There is emerging evidence which leads us to conclude that increased diversity of vaginal microbiota combined with reduced relative abundance of Lactobacillus spp. is involved in HPV acquisition and persistence and the development of cervical precancer and cancer. In this review, we summarise the current literature and discuss potential mechanisms for the involvement of vaginal microbiota in the evolution of CIN and cervical cancer. The concept of manipulation of vaginal bacterial communities using pre- and probiotics is also discussed as an exciting prospect for the field of cervical pathology.
Alterations in the human intestinal microbiota are linked to conditions including inflammatory bowel disease, irritable bowel syndrome, and obesity. The microbiota also undergoes substantial changes ...at the extremes of life, in infants and older people, the ramifications of which are still being explored. We applied pyrosequencing of over 40,000 16S rRNA gene V4 region amplicons per subject to characterize the fecal microbiota in 161 subjects aged 65 y and older and 9 younger control subjects. The microbiota of each individual subject constituted a unique profile that was separable from all others. In 68% of the individuals, the microbiota was dominated by phylum Bacteroides, with an average proportion of 57% across all 161 baseline samples. Phylum Firmicutes had an average proportion of 40%. The proportions of some phyla and genera associated with disease or health also varied dramatically, including Proteobacteria, Actinobacteria, and FAECALIBACTERIA: The core microbiota of elderly subjects was distinct from that previously established for younger adults, with a greater proportion of Bacteroides spp. and distinct abundance patterns of Clostridium groups. Analyses of 26 fecal microbiota datasets from 3-month follow-up samples indicated that in 85% of the subjects, the microbiota composition was more like the corresponding time-0 sample than any other dataset. We conclude that the fecal microbiota of the elderly shows temporal stability over limited time in the majority of subjects but is characterized by unusual phylum proportions and extreme variability.
A wealth of human studies have demonstrated the importance of gut microbiota to health. Research on non-human animal gut microbiota is now increasing, but what insight does it provide? We reviewed ...650 publications from this burgeoning field (2009-2016) and determined that animals driving this research were predominantly 'domestic' (48.2%), followed by 'model' (37.5%), with least studies on 'wild' (14.3%) animals. Domestic studies largely experimentally perturbed microbiota (81.8%) and studied mammals (47.9%), often to improve animal productivity. Perturbation was also frequently applied to model animals (87.7%), mainly mammals (88.1%), for forward translation of outcomes to human health. In contrast, wild animals largely characterised natural, unperturbed microbiota (79.6%), particularly in pest or pathogen vectoring insects (42.5%). We used network analyses to compare the research foci of each animal group: 'diet' was the main focus in all three, but to different ends: to enhance animal production (domestic), to study non-infectious diseases (model), or to understand microbiota composition (wild). Network metrics quantified model animal studies as the most interdisciplinary, while wild animals incorporated the fewest disciplines. Overall, animal studies, especially model and domestic, cover a broad array of research. Wild animals, however, are the least investigated, but offer under-exploited opportunities to study 'real-life' microbiota.
Ursodeoxycholic acid (UDCA) treatment can reduce itch and lower endogenous serum bile acids in intrahepatic cholestasis of pregnancy (ICP). We sought to determine how it could influence the gut ...environment in ICP to alter enterohepatic signalling. The gut microbiota and bile acid content were determined in faeces from 35 pregnant women (14 with uncomplicated pregnancies and 21 with ICP, 17 receiving UDCA). Faecal bile salt hydrolase activity was measured using a precipitation assay. Serum fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) concentrations were measured following a standardised diet for 21 hours. Women with a high ratio of Bacteroidetes to Firmicutes were more likely to be treated with UDCA (Fisher's exact test p = 0.0178) than those with a lower ratio. Bile salt hydrolase activity was reduced in women with low Bacteroidetes:Firmicutes. Women taking UDCA had higher faecal lithocholic acid (p < 0.0001), with more unconjugated bile acids than women with untreated ICP or uncomplicated pregnancy. UDCA-treatment increased serum FGF19, and reduced C4 (reflecting lower bile acid synthesis). During ICP, UDCA treatment can be associated with enrichment of the gut microbiota with Bacteroidetes. These demonstrate high bile salt hydrolase activity, which deconjugates bile acids enabling secondary modification to FXR agonists, enhancing enterohepatic feedback via FGF19.
Abstract The composition of the gut microbiome represents a very important environmental factor that influences the development of type 1 diabetes (T1D). We have previously shown that MyD88-deficient ...non-obese diabetic (MyD88−/−NOD) mice, that were protected from T1D development, had a different composition of gut microbiota compared to wild type NOD mice. The aim of our study was to investigate whether this protection could be transferred. We demonstrate that transfer of gut microbiota from diabetes-protected MyD88-deficient NOD mice, reduced insulitis and significantly delayed the onset of diabetes. Gut bacteria from MyD88-deficient mice, administered over a 3-week period, starting at 4 weeks of age, stably altered the family composition of the gut microbiome, with principally Lachnospiraceae and Clostridiaceae increased and Lactobacillaceae decreased. The transferred mice had a higher concentration of IgA and TGFβ in the lumen that was accompanied by an increase in CD8+ CD103+ and CD8αβ T cells in the lamina propria of the large intestine. These data indicate not only that gut bacterial composition can be altered after the neonatal/weaning period, but that the composition of the microbiome affects the mucosal immune system and can delay the development of autoimmune diabetes. This result has important implications for the development of probiotic treatment for T1D.
Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with no effective medical therapies. A perturbation of the gut microbiota has been described in association with PSC, and fecal ...microbiota transplantation (FMT) has been reported to restore the microbiome in other disease states. Accordingly, we aimed at evaluating the safety, change in liver enzymes, microbiota, and metabolomic profiles in patients with PSC after FMT.
An open-label pilot study of patients with PSC with concurrent inflammatory bowel disease and alkaline phosphatase (ALP) > 1.5× the upper limit of normal was conducted. The patients underwent a single FMT by colonoscopy. Liver enzyme profiles and stool microbiome and metabolomic analysis were conducted at baseline and weeks 1, 4, 8, 12, and 24 post-FMT. The primary outcome was safety, and the secondary outcome was a decrease in ALP levels ≥50% from baseline by week 24 post-FMT; stool microbiota (by 16S rRNA gene profiling) and metabonomic dynamics were assessed.
Ten patients underwent FMT. Nine patients had ulcerative colitis, and 1 had Crohn's colitis. The mean baseline ALP level was 489 U/L. There were no related adverse events. Overall, 30% (3/10) experienced a ≥50% decrease in ALP levels. The diversity increased in all patients post-FMT, as early as week 1 (P < 0.01). Importantly, abundance of engrafter operational taxonomic units in patients post-FMT correlated with decreased ALP levels (P = 0.02).
To our knowledge, this is the first study to demonstrate that FMT in PSC is safe. In addition, increases in bacterial diversity and engraftment may correlate with an improvement in ALP among patients with PSC.
Background Adverse early life events are associated with a maladaptive stress response system and might increase the vulnerability to disease in later life. Several disorders have been associated ...with early life stress, ranging from depression to irritable bowel syndrome. This makes the identification of the neurobiological substrates that are affected by adverse experiences in early life invaluable. Methods The purpose of this study was to assess the effect of early life stress on the brain-gut axis. Male rat pups were stressed by separating them from their mothers for 3 hours daily between postnatal days 2–12. The control group was left undisturbed with their mothers. Behavior, immune response, stress sensitivity, visceral sensation, and fecal microbiota were analyzed. Results The early life stress increased the number of fecal boli in response to a novel stress. Plasma corticosterone was increased in the maternally separated animals. An increase in the systemic immune response was noted in the stressed animals after an in vitro lipopolysaccharide challenge. Increased visceral sensation was seen in the stressed group. There was an alteration of the fecal microbiota when compared with the control group. Conclusions These results show that this form of early life stress results in an altered brain-gut axis and is therefore an important model for investigating potential mechanistic insights into stress-related disorders including depression and IBS.
Excessive fecal bile acid (BA) loss causes symptoms in a large proportion of people diagnosed with irritable bowel syndrome with diarrhea, a common functional bowel disorder. This BA diarrhea (BAD) ...results from increased hepatic synthesis of BAs, with impaired negative feedback regulation by the ileal hormone fibroblast growth factor 19 (FGF19). In this issue of the JCI, Zhao et al. investigated BA metabolism, including fecal BAs, serum BAs, and FGF19, in patients and controls. They identified associations between fecal bacterial BA metabolism and specific microbiota, especially Clostridium scindens. These findings have been tested in a mouse model using microbiota transplants and antibiotic treatment. This group of organisms has potential as a biomarker for BAD and to be a target for therapy.
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