Patient Experiences at California Crisis Pregnancy Centers: A Mixed-Methods Analysis of Online Crowd-Sourced Reviews, 2010-2019.

OBJECTIVES: Crisis pregnancy centers (CPCs) are nonprofit antiabortion organizations that claim provision of pregnancy resources. With the Reproduction Freedom, Accountability, Comprehensive Care, and Transparency Act repealed, CPCs are no longer mandated to share information on state-funded family planning and abortion services. As patients increasingly seek healthcare guidance online, we evaluated crowd-sourced reviews of CPCs using the social networking site Yelp. METHODS: CPCs were identified with the CPC Map, a geo-based location resource. Of California's 145 CPCs, 84% had Yelp pages, and 619 reviews (2010-2019) were extracted. Thematic codes were individually applied to 220 excerpts and then analyzed in detail using thematic analysis to capture emergent themes related to motivations for and experiences of CPCs. To ensure thematic saturation, we applied a natural language-processing technique called the meaning extraction method to computationally derive themes of discussion from all of the extracted posts. RESULTS: Motivations to seek care from CPCs included pregnancy confirmation, gaps in healthcare coverage, parenting and emotional support, and abortion care. A review of experiences reveal that CPC faith-based practice garnered both positive- and negative-based experiences. Reviewers also articulated inaccurate medical information, lack of transparency, and reduced options at CPCs. CONCLUSIONS: This is the first study to analyze California CPCs using a social media platform. Pregnant patients turn to social media to share experiences about pregnancy resources, to find healthcare providers, and to increase transparency of services. This content provides valuable insight into the concerns of pregnant patients and offers an intimate view of California CPCs at a time when no federal regulations are in place.

Low Testosterone on Social Media: Application of Natural Language Processing to Understand Patients' Perceptions of Hypogonadism and Its Treatment.

BACKGROUND: Despite the results of the Testosterone Trials, physicians remain uncomfortable treating men with hypogonadism. Discouraged, men increasingly turn to social media to discuss medical concerns. OBJECTIVE: The goal of the research was to apply natural language processing (NLP) techniques to social media posts for identification of themes of discussion regarding low testosterone and testosterone replacement therapy (TRT) in order to inform how physicians may better evaluate and counsel patients. METHODS: We retrospectively extracted posts from the Reddit community r/Testosterone from December 2015 through May 2019. We applied an NLP technique called the meaning extraction method with principal component analysis (MEM/PCA) to computationally derive discussion themes. We then performed a prospective analysis of Twitter data (tweets) that contained the terms low testosterone, low T, and testosterone replacement from June through September 2019. RESULTS: A total of 199,335 Reddit posts and 6659 tweets were analyzed. MEM/PCA revealed dominant themes of discussion: symptoms of hypogonadism, seeing a doctor, results of laboratory tests, derogatory comments and insults, TRT medications, and cardiovascular risk. More than 25% of Reddit posts contained the term doctor, and more than 5% urologist. CONCLUSIONS: This study represents the first NLP evaluation of the social media landscape surrounding hypogonadism and TRT. Although physicians traditionally limit their practices to within their clinic walls, the ubiquity of social media demands that physicians understand what patients discuss online. Physicians may do well to bring up online discussions during clinic consultations for low testosterone to pull back the curtain and dispel myths.

Understanding Patient Anxieties in the Social Media Era: Qualitative Analysis and Natural Language Processing of an Online Male Infertility Community.

BACKGROUND: Couples struggling with infertility are increasingly turning to the internet for infertility-related content and to connect with others. Most of the published data on infertility and the internet only address the experiences of women, with limited studies focusing exclusively on internet discussions on male factor infertility. OBJECTIVE: The aim of this study was to understand the concerns and experiences of discussants on an online male infertility community and to provide insight into their perceptions of interactions with health care professionals. METHODS: Using the large-scale data analytics tool BigQuery, we extracted all posts in the r/MaleInfertility community (877 members) of the social media website and discussion board Reddit from November 2017 to October 2018. We performed a qualitative thematic analysis and quantitative semantic analysis using Language Inquiry and Word Count 2015 of the extracted posts to identify dominant themes and subthemes of discussions. Descriptive statistics and semantic analytic Z-scores were computed. RESULTS: From the analysis of 97 posts, notable themes and subthemes emerged: 70 (72%) posts shared personal experiences, including feeling emasculated or isolated or describing a negative (28/97, 29%), positive (13/97, 13%), or neutral (56/97, 58%) experience with a health care professional; 19% (18/97) of the posts posed questions about personal semen analysis results. On the basis of semantic analysis, posts by men had higher authenticity scores (Z=3.44; P<.001), suggesting more honest or personal texts, but lower clout scores (Z=4.57; P<.001), suggesting a more tentative or anxious style of writing, compared with posts by women. CONCLUSIONS: To our knowledge, this study represents the first evaluation of a social media community focused exclusively on male infertility using mixed methodology. These results suggest a role for physicians on social media to engage with patients and connect them to accurate resources, in addition to opportunities to improve in-office patient education.

The Gut-Brain Axis and the Microbiome: Mechanisms and Clinical Implications.

BACKGROUND & AIMS: Based largely on results from preclinical studies, the concept of a brain gut microbiome axis has been established, mediating bidirectional communication between the gut, its microbiome, and the nervous system. Limited data obtained in human beings suggest that alterations in these interactions may play a role in several brain gut disorders. METHODS: We reviewed the preclinical and clinical literature related to the topic of brain gut microbiome interactions. RESULTS: Well-characterized bidirectional communication channels, involving neural, endocrine, and inflammatory mechanisms, exist between the gut and the brain. Communication through these channels may be modulated by variations in the permeability of the intestinal wall and the blood-brain barrier. Brain gut microbiome interactions are programmed during the first 3 years of life, including the prenatal period, but can be modulated by diet, medications, and stress throughout life. Based on correlational studies, alterations in these interactions have been implicated in the regulation of food intake, obesity, and in irritable bowel syndrome, even though causality remains to be established. CONCLUSIONS: Targets within the brain gut microbiome axis have the potential to become targets for novel drug development for brain gut disorders.

Anaerobic biosynthesis of the lower ligand of vitamin B12.

Vitamin B12 (cobalamin) is required by humans and other organisms for diverse metabolic processes, although only a subset of prokaryotes is capable of synthesizing B12 and other cobamide cofactors. The complete aerobic and anaerobic pathways for the de novo biosynthesis of B12 are known, with the exception of the steps leading to the anaerobic biosynthesis of the lower ligand, 5,6-dimethylbenzimidazole (DMB). Here, we report the identification and characterization of the complete pathway for anaerobic DMB biosynthesis. This pathway, identified in the obligate anaerobic bacterium Eubacterium limosum, is composed of five previously uncharacterized genes, bzaABCDE, that together direct DMB production when expressed in anaerobically cultured Escherichia coli. Expression of different combinations of the bza genes revealed that 5-hydroxybenzimidazole, 5-methoxybenzimidazole, and 5-methoxy-6-methylbenzimidazole, all of which are lower ligands of cobamides produced by other organisms, are intermediates in the pathway. The bza gene content of several bacterial and archaeal genomes is consistent with experimentally determined structures of the benzimidazoles produced by these organisms, indicating that these genes can be used to predict cobamide structure. The identification of the bza genes thus represents the last remaining unknown component of the biosynthetic pathway for not only B12 itself, but also for three other cobamide lower ligands whose biosynthesis was previously unknown. Given the importance of cobamides in environmental, industrial, and human-associated microbial metabolism, the ability to predict cobamide structure may lead to an improved ability to understand and manipulate microbial metabolism.

Decreased SMG7 expression associates with lupus-risk variants and elevated antinuclear antibody production.

OBJECTIVES: Following up the systemic lupus erythematosus (SLE) genome-wide association studies (GWAS) identification of NMNAT2 at rs2022013, we fine-mapped its 150 kb flanking regions containing NMNAT2 and SMG7 in a 15 292 case-control multi-ancestry population and tested functions of identified variants. METHODS: We performed genotyping using custom array, imputation by IMPUTE 2.1.2 and allele specific functions using quantitative real-time PCR and luciferase reporter transfections. SLE peripheral blood mononuclear cells (PBMCs) were cultured with small interfering RNAs to measure antinuclear antibody (ANA) and cyto/chemokine levels in supernatants using ELISA. RESULTS: We confirmed association at NMNAT2 in European American (EA) and Amerindian/Hispanic ancestries, and identified independent signal at SMG7 tagged by rs2702178 in EA only (p=2.4×10-8, OR=1.23 (95% CI 1.14 to 1.32)). In complete linkage disequilibrium with rs2702178, rs2275675 in the promoter region robustly associated with SMG7 mRNA levels in multiple expression quantitative trait locus (eQTL) datasets. Its risk allele was dose-dependently associated with decreased SMG7 mRNA levels in PBMCs of 86 patients with SLE and 119 controls (p=1.1×10-3 and 6.8×10-8, respectively) and conferred reduced transcription activity in transfected HEK-293 (human embryonic kidney cell line) and Raji cells (p=0.0035 and 0.0037, respectively). As a critical component in the nonsense-mediated mRNA decay pathway, SMG7 could regulate autoantigens including ribonucleoprotein (RNP) and Smith (Sm). We showed SMG7 mRNA levels in PBMCs correlated inversely with ANA titres of patients with SLE (r=-0.31, p=0.01), and SMG7 knockdown increased levels of ANA IgG and chemokine (C-C motif) ligand 19 in SLE PBMCs (p=2.0×10-5 and 2.0×10-4, respectively). CONCLUSION: We confirmed NMNAT2 and identified independent SMG7 association with SLE. The inverse relationship between levels of the risk allele-associated SMG7 mRNAs and ANA suggested the novel contribution of mRNA surveillance pathway to SLE pathogenesis.

Regiospecific formation of cobamide isomers is directed by CobT.

Cobamides, which include vitamin B12 (cobalamin), are a class of modified tetrapyrroles synthesized exclusively by prokaryotes that function as cofactors for diverse biological processes. Cobamides contain a centrally bound cobalt ion that coordinates to upper and lower axial ligands. The lower ligand is covalently linked to a phosphoribosyl moiety through an alpha-glycosidic bond formed by the CobT enzyme. CobT can catalyze the phosphoribosylation of a variety of substrates. We investigated the ability of CobT to act on either of two nitrogen atoms within a single, asymmetric benzimidazole substrate to form two isomeric riboside phosphate products. Reactions containing asymmetric benzimidazoles as substrates for homologues of CobT from different bacteria resulted in the production of distinct ratios of two isomeric products, with some CobT homologues favoring the production of a single isomer and others forming a mixture of products. These preferences were reflected in the production of cobamide isomers with lower ligands attached in different orientations, some of which are novel cobamides that have not been characterized previously. Two isomers of methoxybenzimidazolylcobamide were found to be unequal in their ability to support ethanolamine ammonia-lyase dependent growth in Salmonella enterica, suggesting that CobT's regiospecificity could be biologically important. We also observed differences in pKa, which can influence the reactivity of the cofactor and could contribute to these distinct biological activities. Relaxed regiospecificity was achieved by introducing a single point mutation in an active site residue of CobT. These new cobamide isomers could be used to probe the mechanisms of cobamide-dependent enzymes.

Collagenase Clostridium histolyticum for Peyronie's disease: a contemporary atlas of complications and their management.

INTRODUCTION: Collagenase Clostridium histolyticum (CCH) remains the only Food and Drug Administration-approved medical treatment for Peyronie's disease (PD). The initial IMPRESS I and II trials (Investigation for Maximal Peyronie's Reduction Efficacy and Safety), which led to Food and Drug Administration approval, revealed a rate of treatment-related adverse events as high as 84%. Studies fail to provide clear definitions of complications. OBJECTIVES: To review complications, provide a CCH complication atlas, and propose management strategies for commonly encountered complications. METHODS: We performed a literature review using PubMed. A photographic atlas was provided regarding complications in patients in a high-volume CCH center for PD. RESULTS: Complications were identified and classified by nature and severity. We followed a standardized previously published grading system for hematomas. Complications include bruising, swelling, hematoma formation, back pain, and, rarely, corporal rupture. Complications were discussed, and hematomas were graded by penile surface area. Complication photographs were graded and displayed. Treatment-related adverse effects do not affect overall results. CONCLUSION: Recognizing and grading complications associated with CCH therapy for PD is crucial for effective patient management and informed decision making. A standardized grading system allows for consistency in reporting and comparing hematoma complication rates across studies and patient populations. Herein we provide images that will help clinicians identify and confidently manage common complications that may occur in any CCH program.

Combination clomiphene citrate and anastrozole duotherapy improves semen parameters in a multi-institutional, retrospective cohort of infertile men.

In men with impaired semen parameters, empiric medical therapies such as clomiphene citrate, a selective estrogen receptor modulator (SERM), and anastrozole, a selective aromatase inhibitor, are often employed. The effects of jointly administering these agents on semen parameters are not well understood. Here, we describe the findings of our multi-center, retrospective cohort study of men with idiopathic primary or secondary infertility. Twenty-one men were treated with combination therapy (anastrozole and clomiphene) and 69 men were treated with monotherapy (anastrozole). Patients with pre-treatment normozoospermia and recent or current exogenous testosterone therapy were excluded. Baseline and post-treatment semen and sex hormone parameters were compared among groups. The median follow-up duration was 91 days [interquartile range (IQR), 64-117 days]. Following treatment, 43% of men in the combination therapy group demonstrated normozoospermia, compared to 25% in the monotherapy group. Furthermore, men in the combined group demonstrated marked improvements in total motile sperm count (TMSC) [11.3 vs. 2.1 million (M), P=0.03]. There were no significant differences in hormone levels among the two groups following treatment. Combination therapy with clomiphene citrate and anastrozole was associated with modest benefits in post-treatment semen parameters, when compared to anastrozole monotherapy. These benefits may contribute to improvements in pregnancy outcomes with less invasive assisted reproductive technologies, such as intrauterine insemination (IUI). Future investigations with larger sample sizes and prospective study designs are necessary.

Semen microbiota are dramatically altered in men with abnormal sperm parameters.

There has recently been an explosion of studies implicating the human microbiome in playing a critical role in many disease and wellness states. The etiology of abnormal semen analysis (SA) parameters is not identified in 30% of cases; investigations involving the semen microbiome may bridge this gap. Here, we explore the relationship between the semen microbiome and alterations of sperm parameters. We recruited men presenting for fertility evaluation or vasectomy consultation with proven biological paternity. SA and next generation sequencing was performed. Differential abundance testing using Analysis of composition of Microbiota with Bias Correction (ANCOM-BC) was performed along with canonical correlational analysis for microbial community profiling. Men with abnormal (N = 27) sperm motility showed a higher abundance of Lactobacillus iners compared to those with normal (N = 46) sperm motility (mean proportion 9.4% versus 2.6%, p = 0.046). This relationship persisted on canonical correlational analysis (r = 0.392, p = 0.011). Men with abnormal sperm concentration (N = 20) showed a higher abundance of Pseudomonas stutzeri (2.1% versus 1.0%, p = 0.024) and Pseudomonas fluorescens (0.9% versus 0.7%, p = 0.010), but a lower abundance of Pseudomonas putida (0.5% versus 0.8%, p = 0.020), compared to those with normal sperm concentration (N = 53). Major limitations are related to study design (cross-sectional, observational). Our results suggest that a small group of microorganisms may play a critical role in observed perturbations of SA parameters. Some of these microbes, most notably Lactobacillus iners, have been described extensively within other, fertility-related, contexts, whereas for others, this is the first report where they have potentially been implicated. Advances in our understanding of the semen microbiome may contribute to potentially new therapeutic avenues for correcting impairments in sperm parameters and improving male fertility.

Urine microbes and predictive metagenomic profiles associate with abnormalities in sperm parameters: implications for male subfertility.

OBJECTIVE: To explore the taxonomic and predicted functional relationship between the urine microbiome and alterations of semen analysis (SA) parameters. DESIGN: Cross-sectional study. SETTING: Academic medical center. PATIENT(S): Men presenting for fertility evaluation or men presenting for vasectomy consultation with proven biological paternity were recruited and stratified on the basis of alterations, or lack thereof, in SA parameters. MAIN OUTCOME MEASURE: Changes in the functional and taxonomic urine microbiome profiles of participants with or without alterations in SA parameters. RESULTS: Seventy-three participants were included in our study. Men with abnormal sperm motility (N = 27) showed a nearly 50-fold higher abundance of Dialister micraerophilus compared with those with normal sperm motility (N = 46). This relationship persisted on canonical correlational analysis (r = 0.439). Men with abnormal sperm concentration (N = 20) showed a lower abundance of Enterococcus faecalis and Staphylococcus aureus, compared with those with normal sperm concentration (N = 53). The urine of participants with impaired sperm motility demonstrated dramatic differences in predictive functional profiles in pathways involved in oxidation-reduction balance and cell longevity. CONCLUSIONS: Our findings underscore differences in the urinary microbiome and abnormalities in semen parameters, especially sperm motility. By incorporating predictive functional profiling, we also highlight possible mechanisms that may drive the observed differences in sperm parameters.

Temporal Changes of Clomiphene on Testosterone Levels and Semen Parameters in Subfertile Men.

PURPOSE: Clomiphene citrate (CC) is prescribed off-label in men to improve testosterone and sperm parameters, but the duration of treatment needed to reach maximal benefit remains unclear. Our objective was to examine temporal effects of CC on total testosterone (TT) and semen analysis (SA) using longitudinal follow-up data in treated men. MATERIALS AND METHODS: We analyzed an IRB-approved database of men treated with CC (25 mg q.d. or 50 mg q.o.d.) from January 2016 through May 2021. We identified patients with 3, 6, 9, and 12 month follow-up data for TT and 3, 6, and 9 month follow-up SA. Mean absolute changes in TT and sperm concentration compared to baseline were calculated, along with 95% confidence intervals. Men with prior genitourinary procedures or hormone therapy were excluded. Paired t-tests were used to compare TT and sperm concentration at each time point to baseline (alpha=0.05). RESULTS: One hundered thirty-four men received CC, mean age 37.7 years (SD 6.7, range 24-52). TT at all follow-ups (3, 6, 9, and 12 months) were available for 25 men, and SA at 3, 6, and 9 months for 26 men. Baseline TT was 358±145 ng/dL and sperm concentration was 13±17.2 M/mL. Significant improvement in TT was identified at 3 months (62.7 ng/dL, 95% CI: 0.49-125.0, p=0.048), additional benefit at 6 months (181.8 ng/dL, 95% CI: 114.1-249.5, p<0.01), and plateau at 9 and 12 months. Improvement in sperm concentration was first observed at 9 months (20.7 M/mL, 95% CI: 10.2-31.2, p<0.01). Semen volume and sperm motility did not change. CONCLUSIONS: Duration of treatment with clomiphene may impact testosterone and sperm concentration, and the historical 3 month milestone may be insufficient for clinical and research evaluation. Men taking CC may experience plateau in TT at 6 months and first benefit in sperm concentration at 9 months.

Cannabis and male sexual health: contemporary qualitative review and insight into perspectives of young men on the internet.

INTRODUCTION: Cannabis use is increasing across the United States, yet its short- and long-term effects on sexual function remain controversial. Currently, there is a paucity of studies exploring the relationship between cannabis and men's health. OBJECTIVES: To summarize the available literature on cannabis and men's health and provide insight into lay perceptions of this topic. METHODS: We performed a qualitative PubMed review of the existing literature on cannabis and men's health according to the PRISMA guidelines. Separately, we analyzed relevant themes in online men's health forums. We utilized a Google cloud-based platform (BigQuery) to extract relevant posts from 5 men's health Reddit forums from August 2018 to August 2019. We conducted a qualitative thematic analysis of the posts and quantitatively analyzed them using natural language processing and a meaning extraction method with principal component analysis. RESULTS: Our literature review revealed a mix of animal and human studies demonstrating the negative effects of cannabis on semen parameters and varying effects on erectile function and hormone levels. In our analysis of 372 686 Reddit posts, 1190 (0.3%) included relevant discussion on cannabis and men's health. An overall 272 posts were manually analyzed, showing that online discussions revolve around seeking answers and sharing the effects of cannabis on various aspects of sexual health and quality of life, often with conflicting experiences. Quantitative analysis revealed 1 thematic cluster related to cannabis, insecurity, and mental/physical health. CONCLUSIONS: There is a limited number of quality human studies investigating the effects of cannabis on men's health. Men online are uncertain about how cannabis affects their sexual health and seek more information. As the prevalence of cannabis use increases, so does the need for research in this area.

Identifying Targets for Innovation in Amazon Reviews of Bedwetting Alarms: Thematic Analysis.

BACKGROUND: Nocturnal enuresis (NE) is a frequent diagnosis in pediatric and adolescent populations with an estimated prevalence of around 15% at the age of 6 years. NE can have a substantial impact on multiple health domains. Bedwetting alarms, which typically consist of a sensor and moisture-activated alarm, are a common treatment. OBJECTIVE: This study aimed to determine areas of satisfaction versus dissatisfaction reported by the parents and caregivers of children using current bedwetting alarms. METHODS: Using the search term "bedwetting alarms" on the Amazon marketplace, products with >300 reviews were included. For each product, the 5 reviews ranked the "most helpful" for each star category were selected for analysis. Meaning extraction method was applied to identify major themes and subthemes. A percent skew was calculated by summing the total number of mentions of each subtheme,+1 for a positive mention, 0 for a neutral mention, and -1 for a negative mention, and dividing this total by the number of reviews in which that particular subtheme was observed. Subanalyses were performed for age and gender. RESULTS: Of 136 products identified, 10 were evaluated based on the selection criteria. The main themes identified across products were long-term concerns, marketing, alarm systems, and device mechanics and features. The subthemes identified as future targets for innovation included alarm accuracy, volume variability, durability, user-friendliness, and adaptability to girls. In general, durability, alarm accuracy, and comfort were the most negatively skewed subthemes (with a negative skew of -23.6%, -20.0%, and -12.4% respectively), which are indicative of potential areas for improvement. Effectiveness was the only substantially positively skewed subtheme (16.8%). Alarm sound and device features were positively skewed for older children, whereas ease of use had a negative skew for younger children. Girls and their caretakers reported negative experiences with devices that featured cords, arm bands, and sensor pads. CONCLUSIONS: This analysis provides an innovation roadmap for future device design to improve patient and caregiver satisfaction and compliance with bedwetting alarms. Our results highlight the need for additional options in alarm sound features, as children of different ages have divergent preferences in this domain. Additionally, girls and their parents and caretakers provided more negative overall reviews regarding the range of current device features compared to boys, indicating a potential focus area for future development. The percent skew showed that subthemes were often more negatively skewed toward girls, with the ease of use being -10.7% skewed for boys versus -20.5% for girls, and comfort being -7.1% skewed for boys versus -29.4% for girls. Put together, this review highlights multiple device features that are targets for innovation to ensure translational efficacy regardless of age, gender, or specific family needs.

Guideline-Nonconformant Investigational Treatments for Erectile Dysfunction: What are Patients Learning?

OBJECTIVE: To evaluate the validity of YouTube content on shockwave, platelet-rich plasma, and stem cell therapies for erectile dysfunction (ED). The consumerization of men's health is particularly notable among regenerative ED treatments, and the popularity of these treatments has been amplified by social media sites such as YouTube. METHODS: We searched YouTube utilizing the following terms: "shockwave therapy-," "platelet-rich plasma- and "stem cell therapy-" "-for erectile dysfunction." The first 50 resulting videos per query were screened (inclusion criteria: relevant title/content, English language, >100 views) and judged by 2 independent graders using the validated DISCERN instrument for consumer health information. Regression analysis assessed association of video characteristics with DISCERN score. RESULTS: Seventy-one unique videos met criteria. More content featured non-physicians (37%) or non-urologist physicians (35%) than urologists (28%). Mean DISCERN score was low at 42.8 of 80. DISCERN score significantly differed by video category and characteristics. Educational and urologist-featuring videos were associated with higher score. News reports were associated with lower score. Only 3 videos mentioned investigational/experimental status of the therapies. Only 2 cited society guidelines. CONCLUSION: Most YouTube videos on regenerative ED therapies are unreliable and from non-urologists. The misrepresentation of proven efficacy may be encouraging patients to seek these still investigational treatments at high fiscal costs to the patient. Videos with urologists were more likely to be higher quality and guideline based. The urological and academic communities should continue to leverage the power of social media to provide evidence-backed consumer health information in this space.

Machine learning model to predict obesity using gut metabolite and brain microstructure data.

A growing body of preclinical and clinical literature suggests that brain-gut-microbiota interactions may contribute to obesity pathogenesis. In this study, we use a machine learning approach to leverage the enormous amount of microstructural neuroimaging and fecal metabolomic data to better understand key drivers of the obese compared to overweight phenotype. Our findings reveal that although gut-derived factors play a role in this distinction, it is primarily brain-directed changes that differentiate obese from overweight individuals. Of the key gut metabolites that emerged from our model, many are likely at least in part derived or influenced by the gut-microbiota, including some amino-acid derivatives. Remarkably, key regions outside of the central nervous system extended reward network emerged as important differentiators, suggesting a role for previously unexplored neural pathways in the pathogenesis of obesity.

A multi-omic brain gut microbiome signature differs between IBS subjects with different bowel habits.

Alterations of the brain-gut-microbiome system (BGM) have been implicated in the pathophysiology of irritable bowel syndrome (IBS), yet bowel habit-specific alterations have not been elucidated. In this cross-sectional study, we apply a systems biology approach to characterize BGM patterns related to predominant bowel habit. Fecal samples and resting state fMRI were obtained from 102 premenopausal women (36 constipation-predominant IBS (IBS-C), 27 diarrhea-predominant IBS (IBS-D), 39 healthy controls (HCs)). Data integration analysis using latent components (DIABLO) was used to integrate data from the phenome, microbiome, metabolome, and resting-state connectome to predict HCs vs IBS-C vs IBS-D. Bloating and visceral sensitivity, distinguishing IBS from HC, were negatively associated with beneficial microbes and connectivity involving the orbitofrontal cortex. This suggests that gut interactions may generate aberrant central autonomic and descending pain pathways in IBS. The connection between IBS symptom duration, key microbes, and caudate connectivity may provide mechanistic insight to the chronicity of pain in IBS. Compared to IBS-C and HCs, IBS-D had higher levels of many key metabolites including tryptophan and phenylalanine, and increased connectivity between the sensorimotor and default mode networks; thus, suggestingan influence on diarrhea, self-related thoughts, and pain perception in IBS-D ('bottom-up' mechanism). IBS-C's microbiome and metabolome resembled HCs, but IBS-C had increased connectivity in the default mode and salience networks compared to IBS-D, which may indicate importance of visceral signals, suggesting a more 'top-down' BGM pathophysiology. These BGM characteristics highlight possible mechanistic differences for variations in the IBS bowel habit phenome. This article is part of the Special Issue on 'Microbiome & the Brain: Mechanisms & Maladies'.

Discrimination exposure impacts unhealthy processing of food cues: crosstalk between the brain and gut.

Experiences of discrimination are associated with adverse health outcomes, including obesity. However, the mechanisms by which discrimination leads to obesity remain unclear. Utilizing multi-omics analyses of neuroimaging and fecal metabolites, we investigated the impact of discrimination exposure on brain reactivity to food images and associated dysregulations in the brain-gut-microbiome system. We show that discrimination is associated with increased food-cue reactivity in frontal-striatal regions involved in reward, motivation and executive control; altered glutamate-pathway metabolites involved in oxidative stress and inflammation as well as preference for unhealthy foods. Associations between discrimination-related brain and gut signatures were skewed towards unhealthy sweet foods after adjusting for age, diet, body mass index, race and socioeconomic status. Discrimination, as a stressor, may contribute to enhanced food-cue reactivity and brain-gut-microbiome disruptions that can promote unhealthy eating behaviors, leading to increased risk for obesity. Treatments that normalize these alterations may benefit individuals who experience discrimination-related stress.