Surgically reshaping the gut microbiome.

The gut microbiota in patients with food allergy, and the skin microbiota in atopic dermatitis patients differ from those of healthy people. We hypothesize that relationships may exist between gut and skin microbiota in patients with allergies. The aim of this study was to determine the possible relationship between gut and skin microbiota in patients with allergies, hence simultaneous analysis of the two compartments of microbiota was performed in infants with and without allergic symptoms. Fifty-nine infants with food allergy and/or atopic dermatitis and 28 healthy children were enrolled in the study. The skin and gut microbiota were evaluated using 16S rRNA gene amplicon sequencing. No significant differences in the α-diversity of dermal or fecal microbiota were observed between allergic and non-allergic infants; however, a significant relationship was found between bacterial community structure and allergy phenotypes, especially in the fecal samples. Certain clinical conditions were associated with characteristic bacterial taxa in the skin and gut microbiota. Positive correlations were found between skin and fecal samples in the abundance of Gemella among allergic infants, and Lactobacillus and Bacteroides among healthy infants. Although infants with allergies and healthy infants demonstrate microbiota with similar α-diversity, some differences in β-diversity and bacterial species abundance can be seen, which may depend on the phenotype of the allergy. For some organisms, their abundance in skin and feces samples may be correlated, and these correlations might serve as indicators of the host’s allergic state.

The secondary metabolites produced by fungi known as mycotoxins, are capable of causing mycotoxicosis (diseases and death) in human and animals. Contamination of feedstuffs as well as food commodities by fungi occurs frequently in a natural manner and is accompanied by the presence of mycotoxins. The occurrence of mycotoxins' contamination is further stimulated by the on-going global warming as reflected in some findings. This review comprehensively discussed the role of mycotoxins (trichothecenes, zearalenone, fumonisins, ochratoxins, and aflatoxins) toward gut health and gut microbiota. Certainly, mycotoxins cause perturbation in the gut, particularly in the intestinal epithelial. Recent insights have generated an entirely new perspective where there is a bi-directional relationship exists between mycotoxins and gut microbiota, thus suggesting that our gut microbiota might be involved in the development of mycotoxicosis. The bacteria–xenobiotic interplay for the host is highlighted in this review article. It is now well established that a healthy gut microbiota is largely responsible for the overall health of the host. Findings revealed that the gut microbiota is capable of eliminating mycotoxin from the host naturally, provided that the host is healthy with a balance gut microbiota. Moreover, mycotoxins have been demonstrated for modulation of gut microbiota composition, and such alteration in gut microbiota can be observed up to species level in some of the studies. Most, if not all, of the reported effects of mycotoxins, are negative in terms of intestinal health, where beneficial bacteria are eliminated accompanied by an increase of the gut pathogen. The interactions between gut microbiota and mycotoxins have a significant role in the development of mycotoxicosis, particularly hepatocellular carcinoma. Such knowledge potentially drives the development of novel and innovative strategies for the prevention and therapy of mycotoxin contamination and mycotoxicosis.

Impact of antibiotic therapy on cutaneous and gut microbiota in Rana dybowskii amphibians: Insights and implications

BackgroundSkin lesions can occur during the progression of pancreatic cancer. With growing attention on the gut-skin axis, these lesions may be linked to the microbiota. Microbiota play a crucial role in skin-related conditions, including hair loss and overall skin health. However, few studies have investigated the dynamic changes in gut and skin microbiota associated with skin lesions during cancer progression. In this study, 16S rRNA gene sequencing was used to investigate the dynamic changes of the gut microbiota in mice without non-depilation (Unepi) and depilation (Epi) after PAN02 cell injection. We also revealed the changes in skin microbiota of Unepi mice (Unepi_D) and Epi mice (Epi_D) after depilation.ResultsOur study found that the alpha diversity significantly increased in Unepi_D, indicating an imbalance in gut microbiota homeostasis. In the skin microbiota, certain genera such as Staphylococcus and Devosia were up-regulated, while others like Lactobacillus were down-regulated. Similarly, in the gut microbiota, Parasutterella was enriched, whereas Blautia showed reduced abundance. In the Epi group, the trend of increasing pathogenic bacteria and decreasing probiotics suggests a disrupted microbial environment that may contribute to skin injury through the gut–skin axis. These findings highlight potential microbial targets for diagnosis and therapeutic intervention in pancreatic cancer-associated skin complications.ConclusionTherefore, our findings provide new insights and references for the prevention and treatment of skin-related diseases in clinical practice. Specific gut and skin microbiota alterations may serve as potential biomarkers or therapeutic targets for managing skin complications in pancreatic cancer patients.Clinical trial numberNot applicable.

ST-segment elevation myocardial infarction (STEMI) is characterized by thrombotic coronary artery occlusions caused by atherosclerotic plaque rupture. The gut microbiome potentially contributes to the pathogenesis of coronary artery diseases. This study investigated the microbial diversity and composition of coronary thrombi in STEMI patients and the composition of the thrombus microbiome relative to that of the oral and gut microbiomes. A case–control study was performed with 22 STEMI patients and 20 age- and sex-matched healthy controls. Coronary thrombi were acquired from STEMI patients via manual thrombus aspiration during primary coronary intervention. Oral swab and stool samples were collected from both groups, and 16S rRNA sequencing and metagenomic microbiome analyses were performed. Microbial DNA was detected in 4 of 22 coronary thrombi. Proteobacteria (p) and Bacteroidetes (p) were the most abundant phyla. The oral and gut microbiomes significantly differed between patients and healthy controls. The patient group presented microbial dysbiosis, as follows: a higher relative abundance of Proteobacteria (p) and Enterobacteriaceae (f) in the gut microbiome and a lower abundance of Firmicutes (p) and Haemophilus (g) in the oral microbiome. Furthermore, 4 significantly abundant genera were observed in the coronary thrombus in the patients: Escherichia, 1.25%; Parabacteroides, 0.25%; Christensenella, 0.0%; and Bacteroides, 7.48%. The present results indicate that the relative abundance of the gut and oral microbiomes was correlated with that of the thrombus microbiome.

Background: The gut and biliary microbiota are important components of the complex microecology system in the human body. However, it is often difficult to obtain bile in clinical practice to manage gallstone diseases, warranting further microbiota research to evaluate the relationship between biliary microbiota and gallstone formation. Aims: We aimed to characterize the diversity and alterations of biliary and gut microbiota in patients with gallstones and analyze their possible correlations to gallstone formation. Methods: We collected gallstones, bile, gallbladder mucosa, and feces from 21 patients with gallstone disease during operation and fecal samples from 20 healthy subjects without gallstones. We performed high-throughput sequencing of the V3-V4 regions of the 16S rRNA gene in the gallstone and control groups and analyzed the final optimization sequence. Results: We identified a total of 23,427 operational taxonomic units. Achromobacter (P = 0.010), Faecalibacterium (P = 0.042), and Lachnospira (P = 0.011) were significantly reduced, while Enterococcus (P = 0.001) was increased in the gallstone group. The diversity and composition between the biliary and gut microbiota in gallstone patients had statistical differences. The diversity of gut microbiota was significantly higher than that of biliary microbiota (P < 0.05). In addition, linear discriminant analysis (LDA) >4 indicated that the characteristic flora was specific to five samples. Prevotella and Proteobacteria had LDA values >4 in the feces and both bile and gallbladder mucosa, respectively, of patients with gallstones. Conclusion: The biliary and gut microbiota of patients with gallstones displayed bacterial heterogeneity. Prevotella and Proteobacteria may serve as biomarkers for dysbacteriosis in patients with gallstones, suggesting that alterations of biliary and gut microbiota are involved in the formation of gallstones. This study highlights the potential application of fecal microbiota transplantation technology in the treatment of gallstone diseases. Relevance for Patients: Microecology of the digestive tract is closely related to the formation of gallstones, providing new ideas for the prevention and treatment of patients with gallstones.

Background Nephrolithiasis (NL) is a common extra-intestinal complication of inflammatory bowel diseases (IBD), often related to enteric hyperoxaluria. Growing evidence highlights the association between NL and gut microbiota, but no data are available on the urinary microbiota in IBD patients. Our study aims to analyse the relationship between diet, urinary lithogenic profile, and gut and urinary microbiota in patients with IBD. Methods We prospectively enrolled consecutive adult patients with IBD. All patients underwent abdominal ultrasound, blood tests and 24h-urine collection for lithogenic profile analysis. Moreover, a nutritional evaluation was performed, and all patients underwent bioimpedance measurement. Urinary and gut microbiota were analysed through 16S rRNA sequencing. Results 60 patients were enrolled: 32 with Crohn’s disease (CD) and 28 with ulcerative colitis (UC). NL was more frequent in CD than in UC (28% vs 14%). In patients with NL, gut microbiota analysis showed a lower relative abundance of Agathobacter (p<0.05) and a reduction in alpha diversity (p<0.05) [figure 1]. No statistically significant difference was found in urinary microbiota composition comparing patients with the presence or absence of NL. Protein (g/die) and phosphorus (mg/die) dietary intake were significantly associated with oxaluria (mg/L) (p=0.032 and p=0.007, respectively). At the same time, protein and calcium (mg/day) intake were significantly associated with NL (p= 0.018 and p= 0.023, respectively). Oxaluria and calcium oxalate relative saturation ratio (RSRCaOx) were significantly higher in CD compared to UC [Table 1]. Conclusion Patients with IBD and NL have distinctive gut microbiota features. CD patients showed a higher prevalence of NL and oxaluria levels than UC. In addition, NL occurrence and oxaluria correlated with some nutritional parameters. Further studies are needed to identify patients with IBD at greater risk of NL by connecting the parameters of the gut microbiota, urinary profile and dietary intake to act on modifiable factors aiming to reduce this risk.

Atopic dermatitis (AD) is a common paediatric skin disease with no satisfactory therapy despite increasing prevalence of the disease. AD is characterized by dysbiosis of gut and skin microbiota. Emerging evidence indicates that manipulation of gut microbiota using functional foods including probiotics and prebiotics can alleviate the AD clinical symptoms. Prebiotics can rebalance the microbial communities by providing a nutrient-rich gut environment for the beneficial commensals to thrive, thus prebiotics supplementation is considered a promising approach for successful modulation of gut microbiota to prevent as well as to treat AD patients. Two murine AD models were successfully generated with hallmarks of human AD including epidermal thickening, mast cells accumulation in skin lesions and a significant increase of total serum immunoglobulin (Ig)E obtained following the onset of AD. The first AD model (N-WASPK5KOi) was generated through postnatal deletion of Neural-Wiskott Aldrich Syndrome Protein (N-WASP) in mice keratinocytes using tamoxifen (TAM)-inducible expression of Cre. The onset of AD starting between 5 to 9 weeks after TAM induction. In the second model, AD was induced in BALB/c mice by repeated topical applications of 2,4-dinitrofluorobenzene (DNFB) to the dorsal skin and ear. We have shown that this DNFB-induced AD model can be reliably generated with three epicutaneous DNFB applications over a two weeks period. Because of its high reproducibility and predictability of AD-like symptoms, relative low cost and shorter time in AD development, DNFB-induced AD mice were chosen as murine AD model for prebiotics intervention study. Next, we demonstrated that olive-derived antioxidant dietary fiber (OADF), a by-product of olive oil production caused significant improvement of AD-like symptoms; reduced serum levels of immunoglobulin (Ig)E, interleukin (IL)-1β, IL-6, CXCL1 and increased serum levels of IL-10. DNFB-induced AD mice had gut microbiota dysbiosis compared with that of healthy controls. We also found that OADF supplementation in AD mice restored gut microbiota balance and increased butyrate production. This change in the gut has implication for the skin through IL-10 mediated anti-inflammatory effects clearly visible in the downregulation of AD-related immune response. In vitro characterization of OADF fermentation profiles by human gut microbiota using SHIME further confirmed its strong butyrate-stimulating effects and also showed its capability to reduce the production of branched SCFA and extend beneficial saccharolytic fermentation towards more distal part of the colon. All together these findings highlight the importance of the gut-skin axis for the AD dietary therapeutic agents and suggest that OADF can be an effective functional food or nutraceutical ingredient for AD patients through beneficially affecting gut microbiota of the host.

Aging-related gut microbiota dysbiosis initiates gut inflammation and microbiota dysbiosis, which induce the occurrence of psychiatric disorders including dementia. The alleviation of gut microbiota dysbiosis by probiotics is suggested to be able to alleviate psychiatric disorders including cognitive impairment (CI). Therefore, to understand how probiotics could alleviate CI, we examined the effects of anti-inflammatory Lactobacillus gasseri NK109 and its supplement (NS, mixture of NK109 and soybean embryo ethanol extract) on cognitive function in aged (Ag), 5XFAD transgenic (Tg), or mildly cognition-impaired adult fecal microbiota (MCF)-transplanted mice. Oral administration of NK109 or NS decreased CI-like behaviors in Ag mice. Their treatments suppressed TNF-α and p16 expression and NF-κB-activated cell populations in the hippocampus and colon, while BDNF expression was induced. Moreover, they partially shifted the β-diversity of gut microbiota in Ag mice to those of young mice: they decreased Bifidobacteriaceae, Lactobacillaceae, and Helicobacteriaceae populations and increased Rikenellaceae and Prevotellaceae populations. Oral administration of NK109 or NS also reduced CI-like behaviors in Tg mice. Their treatments induced BDNF expression in the hippocampus, decreased hippocampal TNF-α and Aβ expression and hippocampal and colonic NF-κB-activated cell populations. NK109 and NS partially shifted the β-diversity of gut microbiota in Tg mice: they decreased Muribaculaceae and Rhodospiraceae populations and increased Helicobacteriaceae population. Oral administration of NK109 or NS decreased MCF transplantation-induced CI-like behaviors in mice. NK109 and NS increased hippocampal BDNF expression, while hippocampal and colonic TNF-α expression and NF-κB-activated cell populations decreased. These findings suggest that dementia can fluctuate the gut microbiota composition and NK109 and its supplement NS can alleviate CI with systemic inflammation by inducing BDNF expression and suppressing NF-κB activation and gut microbiota dysbiosis.

Coronavirus Disease 2019 (COVID-19) is a pandemic disease caused by a new corona virus. COVID-19 affects different people in different ways. COVID-19 could affect the gastrointestinal system via gut microbiota impairment. Gut microbiota could affect lung health through a relationship between gut and lung microbiota, which is named gut-lung axis. Gut microbiota impairment plays a role in pathogenesis of various pulmonary disease states, so GI diseases were found to be associated with respiratory diseases. Moreover, most infected people will develop mild to moderate gastrointestinal (GI) symptoms such as diarrhea, vomiting, and stomachache, which is caused by impairment in gut microbiota. Therefore, the current study aimed to review potential role of gut microbiota in patients with COVID-19, its relation with lung axis, Central Nervous System (CNS) axis and improvement with probiotic therapy. Also, this review can be a guide for potential role of gut microbiota in patients with COVID-19.

ABSTRACTHIV-exposed uninfected infants (HEU) have abnormal immunologic functions and increased infectious morbidity in the first 6 months of life, which gradually decreases thereafter. The mechanisms underlying HEU immune dysfunctions are unknown. We hypothesized that unique characteristics of the HEU gut microbiota associated with maternal HIV status may underlie the HEU immunologic dysfunctions. We characterized the infant gut, maternal gut, and breast milk microbiomes of mother-infant pairs, including 123 with HEU and 117 with HIV-uninfected infants (HUU), from South Africa. Pan-bacterial 16S rRNA gene sequencing was performed on (i) infant stool at 6, 28, and 62 weeks; (ii) maternal stool at delivery and 62 weeks; and (iii) breast milk at 6 weeks. Infant gut alpha and beta diversities were similar between groups. Microbial composition significantly differed, including 12 genera, 5 families and 1 phylum at 6 weeks; 12 genera and 2 families at 28 weeks; and 2 genera and 2 families at 62 weeks of life. Maternal gut microbiomes significantly differed in beta diversity and microbial composition, and breast milk microbiomes differed in microbial composition only. Infant gut microbiotas extensively overlapped with maternal gut and minimally with breast milk microbiotas. Nevertheless, exclusively breastfed HEU and HUU had less divergent microbiomes than nonexclusively breastfed infants. Feeding pattern and maternal gut microbiome imprint the HEU gut microbiome. Compared to HUU, the HEU gut microbiome prominently differs in early infancy, including increased abundance of taxa previously observed to be present in excess in adults with HIV. The HEU and HUU gut microbiome compositions converge over time, mirroring the kinetics of HEU infectious morbidity risk.

The Gut Microbiome and Joint Microbiome Show Alterations in Patients With Knee Osteoarthritis Versus Controls: A Systematic Review

Human gut microbiomes are known to change with age, yet the relative value of human microbiomes across the body as predictors of age, and prediction robustness across populations is unknown. In this study, we tested the ability of the oral, gut, and skin (hand and forehead) microbiomes to predict age in adults using random forest regression on data combined from multiple publicly available studies, evaluating the models in each cohort individually. Intriguingly, the skin microbiome provides the best prediction of age (mean ± standard deviation, 3.8 ± 0.45 years, versus 4.5 ± 0.14 years for the oral microbiome and 11.5 ± 0.12 years for the gut microbiome). This also agrees with forensic studies showing that the skin microbiome predicts postmortem interval better than microbiomes from other body sites. Age prediction models constructed from the hand microbiome generalized to the forehead and vice versa, across cohorts, and results from the gut microbiome generalized across multiple cohorts (United States, United Kingdom, and China). Interestingly, taxa enriched in young individuals (18 to 30 years) tend to be more abundant and more prevalent than taxa enriched in elderly individuals (>60 yrs), suggesting a model in which physiological aging occurs concomitantly with the loss of key taxa over a lifetime, enabling potential microbiome-targeted therapeutic strategies to prevent aging.IMPORTANCE Considerable evidence suggests that the gut microbiome changes with age or even accelerates aging in adults. Whether the age-related changes in the gut microbiome are more or less prominent than those for other body sites and whether predictions can be made about a person's age from a microbiome sample remain unknown. We therefore combined several large studies from different countries to determine which body site's microbiome could most accurately predict age. We found that the skin was the best, on average yielding predictions within 4 years of chronological age. This study sets the stage for future research on the role of the microbiome in accelerating or decelerating the aging process and in the susceptibility for age-related diseases.

Oligofructose (OFS) is a prebiotic that reduces energy intake and fat mass via changes in gut satiety hormones and microbiota. The effects of OFS may vary depending on predisposition to obesity. The aim of this study was to examine the effect of OFS in diet-induced obese (DIO) and diet-resistant (DR) rats. Adult, male DIO, and DR rats were randomized to: high-fat/high-sucrose (HFS) diet or HFS diet + 10% OFS for 6 weeks. Body composition, food intake, gut microbiota, plasma gut hormones, and cannabinoid CB(1) receptor expression in the nodose ganglia were measured. OFS reduced body weight, energy intake, and fat mass in both phenotypes (P < 0.05). Select gut microbiota differed in DIO versus DR rats (P < 0.05), the differences being eliminated by OFS. OFS did not modify plasma ghrelin or CB(1) expression in nodose ganglia, but plasma levels of GIP were reduced and PYY were elevated (P < 0.05) by OFS. OFS was able to reduce body weight and adiposity in both prone and resistant obese phenotypes. OFS-induced changes in gut microbiota profiles in DIO and DR rats, along with changes in gut hormone levels, likely contribute to the sustained lower body weights.

Microbiome research focusing on late and moderate preterm infants (LMPT; 32 to 36 weeks gestation) is limited, despite rising LMPT births, large healthcare burdens, and increased risks of multiple morbidities, potentially microbially related. In this longitudinal cohort study, 16S rRNA gene sequencing was used to analyze 371 stool and 402 saliva samples from 160 LMPT infants, collected at five time points between birth and 12 months corrected age (CA), to describe spatial and temporal variability in gut and oral microbiomes. Paired stool and saliva samples (n = 337) were analyzed for potential microbial relationships. Early LMPT samples (up to 60 days of life; DOL) were also compared with data from seven extremely preterm infants (EP; <28 weeks gestation; stool n = 14, saliva n = 14). LMPT stool and saliva were composed of distinct microbial communities at each time point, and both sample types showed increasing alpha diversity over time. Stool was initially dominated by Escherichia/Shigella, Klebsiella, and Streptococcus, with Bifidobacterium becoming dominant from term equivalent age (TEA). Contrarily, saliva was dominated by Streptococcus throughout the first year, with early contributions from Staphylococcus and later Veillonella. LMPT infants had higher stool and lower saliva diversity compared with EP infants. Both sample types from EP infants were taxonomically distinct from LMPTs, with Escherichia/Shigella dominating both EP sample types throughout the first 60 DOL. The results highlight the unique trajectories of LMPT microbiomes and emphasize the role of gestational maturity in shaping microbial communities.IMPORTANCEThe oral and gut microbiome develops from birth and plays important roles in health. This has been well studied in extremely preterm infants (EP; born <32 weeks gestation) and term infants (born >38 weeks gestation), but there is a paucity of research describing oral and gut microbiome development in late and moderate preterm infants (LMPT; 32 to 36 weeks gestation). Our study analyzed microbiome development in 160 LMPT infants from birth to 12 months corrected age. The results showed distinct microbial communities in stool and saliva, with increasing alpha diversity and niche specification over time. LMPT infants' gut microbiome became dominated by Bifidobacterium by month 3, while the oral community was consistently dominated by Streptococcus. These results highlight that LMPT infants have gut and oral microbiome development that is more like term infants than EP infants, which has important implications for the care of LMPT infants.