Subchronic inhalation exposure to ultrafine particulate matter alters the intestinal microbiome in various mouse models.

Exposure to ultrafine particles (UFPs) has been associated with multiple adverse health effects. Inhaled UFPs could reach the gastrointestinal tract and influence the composition of the gut microbiome. We have previously shown that oral ingestion of UFPs alters the gut microbiome and promotes intestinal inflammation in hyperlipidemic Ldlr-/- mice. Particulate matter (PM)2.5 inhalation studies have also demonstrated microbiome shifts in normolipidemic C57BL/6 mice. However, it is not known whether changes in microbiome precede or follow inflammatory effects in the intestinal mucosa. We hypothesized that inhaled UFPs modulate the gut microbiome prior to the development of intestinal inflammation. We studied the effects of UFP inhalation on the gut microbiome and intestinal mucosa in two hyperlipidemic mouse models (ApoE-/- mice and Ldlr-/- mice) and normolipidemic C57BL/6 mice. Mice were exposed to PM in the ultrafine-size range by inhalation for 6 h a day, 3 times a week for 10 weeks at a concentration of 300-350 µg/m3.16S rRNA gene sequencing was performed to characterize sequential changes in the fecal microbiome during exposures, and changes in the intestinal microbiome at the end. PM exposure led to progressive differentiation of the microbiota over time, associated with increased fecal microbial richness and evenness, altered microbial composition, and differentially abundant microbes by week 10 depending on the mouse model. Cross-sectional analysis of the small intestinal microbiome at week 10 showed significant changes in α-diversity, ß-diversity, and abundances of individual microbial taxa in the two hyperlipidemic models. These alterations of the intestinal microbiome were not accompanied, and therefore could not be caused, by increased intestinal inflammation as determined by histological analysis of small and large intestine, cytokine gene expression, and levels of fecal lipocalin. In conclusion, 10-week inhalation exposures to UFPs induced taxonomic changes in the microbiome of various animal models in the absence of intestinal inflammation.

Preventing patient positioning injuries in the nonoperating room setting.

PURPOSE OF REVIEW: Postprocedural positioning injuries are an under-appreciated source of morbidity for patients. These injuries may not present until days after anesthesia and may be missed for multiple reasons including the distracting injury of the procedural site, illness of the patient, lack of follow-up, and insufficient awareness of this type of injury. Risks for these adverse events are exacerbated in the nonoperating room anesthesia (NORA) population for several reasons. These patients tend to be older and sicker than patients presenting to the operating room, increasing the risk of an injury. Proceduralists and anesthesia providers are usually consultants, not the primary care team, so may have limited patient follow-up. This review will discuss the risk factors for position-related injuries and how to prevent them with proper positioning and padding. RECENT FINDINGS: The mainstay of preventing periprocedural positioning injuries is careful positioning of the patient and proper padding of pressure points. This may be particularly challenging because of physical constraints and positioning requirements for NORA procedures, as well as preference for radiolucent positioning materials. Recent studies have shown the potential benefit of monitoring somatosensory evoked potentials (SSEP) in high-risk patients. SUMMARY: Careful consideration of patient positioning and thorough understanding of peripheral nerve and pressure injuries is essential for anesthesia providers to avoid positioning injuries during NORA procedures. VIDEO ABSTRACT: http://links.lww.com/COAN/A87.

Microbial changes from bariatric surgery alters glucose-dependent insulinotropic polypeptide and prevents fatty liver disease.

Bariatric surgery remains a potent therapy for nonalcoholic fatty liver disease (NAFLD), but its inherent risk and eligibility requirement limit its adoption. Therefore, understanding how bariatric surgery improves NAFLD is paramount to developing novel therapeutics. Here, we show that the microbiome changes induced by sleeve gastrectomy (SG) reduce glucose-dependent insulinotropic polypeptide (GIP) signaling and confer resistance against diet-induced obesity (DIO) and NAFLD. We examined a cohort of NALFD patients undergoing SG and evaluated their microbiome, serum metabolites, and GI hormones. We observed significant changes in Bacteroides, lipid-related metabolites, and reduction in GIP. To examine if the changes in the microbiome were causally related to NAFLD, we performed fecal microbial transplants in antibiotic-treated mice from patients before and after their surgery who had significant weight loss and improvement of their NAFLD. Mice transplanted with the microbiome of patients after bariatric surgery were more resistant to DIO and NAFLD development compared to mice transplanted with the microbiome of patients before surgery. This resistance to DIO and NAFLD was also associated with a reduction in GIP levels in mice with post-bariatric microbiome. We further show that the reduction in GIP was related to higher levels of Akkermansia and differing levels of indolepropionate, bacteria-derived tryptophan-related metabolite. Overall, this is one of the few studies showing that GIP signaling is altered by the gut microbiome, and it supports that the positive effect of bariatric surgery on NAFLD is in part due to microbiome changes.

Transcriptome and Gut Microbiota Profiling Revealed the Protective Effect of Tibetan Tea on Ulcerative Colitis in Mice.

Traditionally, Ya'an Tibetan tea is routinely consumed by local people in the Tibet region. It is believed to possess promising anti-inflammatory benefits. This study was conducted to elucidate the protective impact of Tibetan tea extract (TTE) on dextran sodium sulfate (DSS)-induced colitis in mice. Mice were split into four groups: control (C) group, Tibetan tea (T) group, DSS-induced model (CD) group, and Tibetan tea + DSS (TD) group. The intake of TTE significantly reduced the clinical symptoms of ulcerative colitis (UC) by alleviating the impact of cellular damage and reducing glandular hypertrophy and the infiltration of inflammatory cells. UC led to a prominent shift of the microbial communities in the gut. Interestingly, the beneficial microbes, such as Lactobacillus reuteri, Bifidobacterium choerinum, and Lactobacillus intestinalis, were significantly increased in TTE-treated mice when compared to any other experimental group. The transcriptome analysis revealed that the positive effect of TTE on UC could be attributed to changes in the G alpha (i) signaling pathway and the innate immune system. The genes related to inflammation and immune system pathways were differentially expressed in the TTE-treated group. Moreover, the relative expression of genes linked to the inflammatory TLR4/MyD88/NF-κB signaling pathway was significantly downregulated toward the level of normal control samples in the TD group. Overall, this study revealed the modulatory effect by which TTE reversed the development and severity of chronic colon damage.

The Panda-Derived Lactobacillus plantarum G201683 Alleviates the Inflammatory Response in DSS-Induced Panda Microbiota-Associated Mice.

Intestinal diseases are one of the main causes of captive giant panda death. Their special dietary habits and gastrointestinal tract structure often lead to intestinal epithelium damage and secondary intestinal infection. The captive giant panda is predisposed to suffer from microbiota dysbiosis due to long-term artificial feeding and antibiotic misuse. However, there are few reported probiotics to treat giant panda enteritis and the associated dysbiosis. This study aims to elucidate the mechanism by which Lactobacillus plantarum G201683 (L. plantarum G83), a promising panda-derived probiotic, exerts a protective effect on intestinal inflammation in the dextran sulfate sodium- (DSS) induced panda microbiota-associated (DPMA) mouse model. The DPMA mouse was generated by antibiotic treatment and 5% DSS drinking water administration to assess the effect of L. plantarum G83 on intestinal inflammation and microbiota in vivo. Our results demonstrated the successful generation of a DPMA mouse model with Enterobacteriaceae enrichment, consistent with the giant panda intestinal microbiota. L. plantarum G83 decreased clinical and histological severity of intestinal inflammation, enhanced intestinal tight junction protein expression (ZO-1, Occludin) and alleviated inflammatory cytokine production (TNF-) in the colon of DPMA mice. The administration of L. plantarum G83 altered the microbiota composition by decreasing pathogen associated taxa such as E. coli and increasing abundance of beneficial bacteria including Bifidobacterium spp. These changes in microbiota composition were associated with an increased concentration of short chain fatty acids (SCFA), reduced NF-κB signaling, and an altered balance of T helper cell subsets. Our findings support L. plantarum G83 as a promising probiotic to treat intestinal inflammation in the giant panda.

The Intestinal Microbiome Predicts Weight Loss on a Calorie-Restricted Diet and Is Associated With Improved Hepatic Steatosis.

Background: The microbiome has been shown in pre-clinical and epidemiological studies to be important in both the development and treatment of obesity and metabolic associated fatty liver disease (MAFLD). However, few studies have examined the role of the microbiome in the clinical response to calorie restriction. To explore this area, we performed a prospective study examining the association of the intestinal microbiome with weight loss and change in hepatic steatosis on a calorie-restricted diet. Methods: A prospective dietary intervention study of 80 overweight and obese participants was performed at the Greater West Los Angeles Veterans Affair Hospital. Patients were placed on a macronutrient standardized diet for 16 weeks, including 14 weeks of calorie restriction (500 calorie deficit). Body composition analysis by impedance, plasma lipid measurements, and ultrasound elastography to measure hepatic steatosis were performed at baseline and week 16. Intestinal microbiome composition was assessed using 16S rRNA gene sequencing. A per protocol analysis was performed on all subjects completing the trial (n = 46). Results: Study completers showed significant reduction in weight, body mass index, total cholesterol, low density lipoprotein, and triglyceride. Subjects who lost at least 5% of their body weight had significantly greater reduction in serum triglyceride and hepatic steatosis than those with <5% body weight loss. Enterococcus and Klebsiella were reduced at the end of the trial while Coprococcus and Collinsella were increased. There were also significant baseline microbiome differences between patients who had at least 5% weight loss as compared to those that did not. Lachnoclostridium was positively associated with hepatic steatosis and Actinomyces was positively associated with hepatic steatosis and weight. Baseline microbiome profiles were able to predict which patients lost at least 5% of their body weight with an AUROC of 0.80. Conclusion: Calorie restriction alters the intestinal microbiome and improves hepatic steatosis in those who experience significant weight loss. Baseline microbiome differences predict weight loss on a calorie-restricted diet and are associated with improvement in hepatic steatosis, suggesting a role of the gut microbiome in mediating the clinical response to calorie restriction.

Gut microbiome profiles associated with steatosis severity in metabolic associated fatty liver disease.

Aim: The microbiome has been shown to be pivotal in the development of metabolic associated fatty liver disease (MAFLD). Few have examined the relationship of the microbiome specifically with steatosis grade. Therefore, our aim was to characterize the association of the microbiome with MAFLD steatosis severity while adjusting for metabolic comorbidities including diabetes. Methods: We enrolled patients with MAFLD at the West Los Angeles Veterans Affair Hospital. All patients underwent ultrasound elastography, fasting serum collection, and fecal sampling for 16S sequencing. We examined the associations of microbial diversity and composition with advanced steatosis, defined as a CAP score of ≥ 300 dB/m, with or without the presence of metabolic comorbidities. Results: Seventy-five patients were enrolled. African American were less likely to have advanced steatosis than either Hispanics or Whites (P = 0.001). Patients with more advanced steatosis had higher fasting serum triglyceride (192.6 ± 157.1 mg/dL vs. 122.5 ± 57.4 mg/dL), HbA1c (6.7% ± 1.4% vs. 6.1% ± 0.8%), transaminases, and were more likely to have metabolic syndrome (52.4% vs. 24.2%, P = 0.02). Advanced steatosis and diabetes were associated with altered microbial composition. Bacteroides was negatively associated with advanced steatosis while Megasphaera was positively associated with steatosis. Akkermansia was negatively associated with diabetes, while Anaerostipes and Parabacteroides were positively associated with diabetes. Conclusion: Diabetes and metabolic syndrome are associated with hepatic steatosis severity in MAFLD patients and both advanced steatosis and comorbid diabetes are independently associated with microbiome changes. These results provide insight into the role of the gut microbiome in MAFLD associated with metabolic syndrome.

A Distinct Brain-Gut-Microbiome Profile Exists for Females with Obesity and Food Addiction.

BACKGROUND: Alterations in brain-gut-microbiome interactions have been implicated as an important factor in obesity. This study aimed to explore the relationship between food addiction (FA) and the brain-gut-microbiome axis, using a multi-omics approach involving microbiome data, metabolomics, and brain imaging. METHODS: Brain magnetic resonance imaging was obtained in 105 females. FA was defined by using the Yale Food Addiction Scale. Fecal samples were collected for sequencing and metabolomics. Statistical analysis was done by using multivariate analyses and machine learning algorithms. RESULTS: Of the females with obesity, 33.3% exhibited FA as compared with 5.3% and 0.0% of females with overweight and normal BMI, respectively (P = 0.0001). Based on a multilevel sparse partial least square discriminant analysis, there was a difference in the gut microbiome of females with FA versus those without. Differential abundance testing showed Bacteroides, Megamonas, Eubacterium, and Akkermansia were statistically associated with FA (q < 0.05). Metabolomics showed that indolepropionic acid was inversely correlated with FA. FA was also correlated with increased connectivity within the brain's reward network, specifically between the intraparietal sulcus, brain stem, and putamen. CONCLUSIONS: This is the first study to examine FA along the brain-gut-microbiome axis and it supports the idea of targeting the brain-gut-microbiome axis for the treatment of FA and obesity.

A High Protein Calorie Restriction Diet Alters the Gut Microbiome in Obesity.

BACKGROUND: High protein calorie restriction diets have shown clinical efficacy for obesity, but the mechanisms are not fully known. The intestinal microbiome is a mediator of obesity and preclinical data support an effect of high protein diet (HPD) on the gut microbiome of obesity, but there are few studies in humans. METHODS: To address this, we conducted a dietary intervention trial of 80 overweight and obese subjects who were randomized to a calorie-restricted high protein diet (HPD) (30% calorie intake) or calorie-restricted normal protein diet (NPD) (15%) for 8 weeks. Baseline dietary intake patterns were assessed by the Diet History Questionnaire III. Longitudinal fecal sampling was performed at baseline, week 1, week 2, week 4, week 6, and week 8, for a total of 365 samples. Intestinal microbiome composition was assessed by 16S rRNA gene sequencing. RESULTS: At baseline, microbial composition was associated with fiber and protein intake. Subjects on the HPD showed a significant increase in microbial diversity as measured by the Shannon index compared to those on the NPD. The HPD was also associated with significant differences in microbial composition after treatment compared to the NPD. Both diets induced taxonomic shifts compared to baseline, including enrichment of Akkermansia spp. and Bifidobacterium spp. and depletion of Prevotella spp. Conclusion: These findings provide evidence that weight loss diets alter the gut microbiome in obesity and suggest differential effects of HPDs compared to NPDs which may influence the clinical response to HPD.

Preoperative electrocardiograms: patient factors predictive of abnormalities.

BACKGROUND: Age is often the sole criterion for determining the need for preoperative electrocardiograms. However, screening electrocardiograms have not been shown to add value above clinical information. This study was designed to determine whether it is possible to target electrocardiograms ordering to patients most likely to have an abnormality that would affect management and if age alone is predictive of significant electrocardiograms abnormalities. METHODS: A list was developed of electrocardiograms abnormalities considered significant enough to impact management, as well as a list of patient factors believed to increase cardiovascular risk. electrocardiograms in all patients over 50 yr of age presenting for preoperative evaluation during a 2-month period were reviewed. RESULTS: A total of 1,149 electrocardiograms were reviewed, with 89 patients (7.8%) having at least one significant abnormality. These patients were compared with a group of 195 patients who had electrocardiograms that did not contain significant abnormalities. Patients at higher risk of having a significantly abnormal electrocardiograms that would potentially affect management were those older than 65 yr of age or who had a history of heart failure, high cholesterol, angina, myocardial infarction, or severe valvular disease. Five patients (0.44%) had an abnormal electrocardiograms in the absence of risk factors. The sensitivity of the model is 87.6%. CONCLUSION: Age greater than 65 yr remains an independent predictor for significant preoperative electrocardiograms abnormalities. The specific clinical risk factors that were found have a high sensitivity and identified all but 0.44% of patients with electrocardiograms abnormalities that may affect preoperative management.

Unusual finding on bronchoscopy: trauma patient identified as a body stuffer.

We present the case of a trauma patient whose persistently abnormal chest radiography led to exploratory bronchoscopy. After the discovery of a foreign body in the right lower lobe bronchus, an attempted retrieval resulted in accidental perforation of a cocaine bag and release of the drug, which may have been the cause of the patient's subsequent pneumonitis.