Color Flow Ultrasound Spatial Sampling Beam Density for Partial Volume-Corrected Three-Dimensional Volume Flow (3DVF): Theory, Simulation, and Experiment.

OBJECTIVE: The purpose of this study was to quantify the accuracy of partial volume-corrected three-dimensional volume flow (3DVF) measurements as a function of spatial sampling beam density using carefully-designed parametric analyses in order to inform the target applications of 3DVF. METHODS: Experimental investigations employed a mechanically-swept curvilinear ultrasound array to acquire 3D color flow (6.3 MHz) images in flow phantoms consisting of four lumen diameters (6.35, 4.88, 3.18 and 1.65 mm) with volume flow rates of 440, 260, 110 and 30 mL/min, respectively. Partial volume-corrected three-dimensional volume flow (3DVF) measurements, based on the Gaussian surface integration principle, were computed at five regions of interest positioned between depths of 2 and 6 cm in 1 cm increments. At each depth, the color flow beam point spread function (PSF) was also determined, using in-phase/quadrature data, such that 3DVF bias could then be related to spatial sampling beam density. Corresponding simulations were performed for a laminar parabolic flow profile that was sampled using the experimentally-measured PSFs. Volume flow was computed for all combinations of lumen diameters and the PSFs at each depth. RESULTS: Accurate 3DVF measurements, i.e., bias less than ±20%, were achieved for spatial sampling beam densities where at least 6 elevational color flow beams could be positioned across the lumen. In these cases, greater than 8 lateral color flow beams were present. PSF measurements showed an average lateral-to-elevational beam width asymmetry of 1:2. Volume flow measurement bias increased as the color flow beam spatial sampling density within the lumen decreased. CONCLUSION: Applications of 3DVF, particularly those in the clinical domain, should focus on areas where a spatial sampling density of 6 × 6 (lateral x elevational) beams can be realized in order to minimize measurement bias. Matrix-based ultrasound arrays that possess symmetric PSFs may be advantageous to achieve adequate beam densities in smaller vessels.

Social Determinants of Health and Parenting Self-Efficacy Among Mothers of Preterm Infants.

Objective: To explore the relationships between social and environmental factors and parenting self-efficacy (PSE) among mothers of preterm infants hospitalized in neonatal intensive care units (NICUs) using a social determinants of health (SDoH) framework. Method: We analyzed data from a prospective cohort study that included 187 mother-infant dyads admitted to four NICUs in the Mountain West region between June 2017 and December 2019. We used multivariable linear regression models to assess the independent associations between maternal and infant characteristics and PSE. Results: Our final multiple linear regression model predicting the efficacy score including maternal race/ethnicity, age, insurance, employment status before giving birth, gestational age, depression, and having other children was significant (F(12,160) = 3.17, p = .0004, adjusted R¬2 = .131). Significant predictors of PSE were race/ethnicity (ß= 3.3, p = .022), having another child/children (ß= 4.2, p = .005), and depression (ß= -4.2, p = .004). Conclusions: Findings suggest that social workers and medical practitioners should consider SDoH, such as insurance type, household income, and employment, along with traditional clinical indicators when assessing families' infant care needs. Social workers, medical practitioners, and researchers should be mindful of how implicit bias may influence the allocation of care and parental supports.

International Genetic Testing and Counseling Practices for Parkinson's Disease.

BACKGROUND: There is growing clinical and research utilization of genetic testing in Parkinson's disease (PD), including direct-to-consumer testing. OBJECTIVES: The aim is to determine the international landscape of genetic testing in PD to inform future worldwide recommendations. METHODS: A web-based survey assessing current practices, concerns, and barriers to genetic testing and counseling was administered to the International Parkinson and Movement Disorders Society membership. RESULTS: Common hurdles across sites included cost and access to genetic testing, and counseling, as well as education on genetic counseling. Region-dependent differences in access to and availability of testing and counseling were most notable in Africa. High-income countries also demonstrated heterogeneity, with European nations more likely to have genetic testing covered through insurance than Pan-American and Asian countries. CONCLUSIONS: This survey highlights not only diversity of barriers in different regions but also the shared and highly actionable needs for improved education and access to genetic counseling and testing for PD worldwide. © 2023 International Parkinson and Movement Disorder Society.

Providing genetic testing and genetic counseling for Parkinson's disease to the community.

PURPOSE: To evaluate the feasibility and impact of offering genetic testing and counseling to patients with Parkinson's disease (PD), with the potential to enroll in gene-targeted clinical trials and improve clinical care. METHODS: A multicenter, exploratory pilot study at 7 academic hospital sites in the United States tracked enrollment and randomized participants to receive results and genetic counseling at local sites or by genetic counselors, remotely. Follow-up surveys measured participant/provider satisfaction, knowledge, and psychological impact. RESULTS: From September 5, 2019 to January 4, 2021, 620 participants were enrolled and 387 completed outcome surveys. There were no significant differences in outcomes between local and remote sites, with both arms reporting high knowledge and satisfaction scores (>80%). Notably, 16% of those tested had reportable PD gene variants (pathogenic/likely pathogenic/risk allele). CONCLUSION: Local clinicians, as well as genetic counselors, with educational support as needed, can effectively return genetic results for PD as we observed favorable outcome measures in both groups. Increasing access to PD genetic testing and counseling is urgent; this can inform future efforts to integrate genetic testing and counseling into clinical care for all those with PD.

Genetic Testing in Parkinson's Disease.

Genetic testing for persons with Parkinson's disease is becoming increasingly common. Significant gains have been made regarding genetic testing methods, and testing is becoming more readily available in clinical, research, and direct-to-consumer settings. Although the potential utility of clinical testing is expanding, there are currently no proven gene-targeted therapies, but clinical trials are underway. Furthermore, genetic testing practices vary widely, as do knowledge and attitudes of relevant stakeholders. The specter of testing mandates financial, ethical, and physician engagement, and there is a need for guidelines to help navigate the myriad of challenges. However, to develop guidelines, gaps and controversies need to be clearly identified and analyzed. To this end, we first reviewed recent literature and subsequently identified gaps and controversies, some of which were partially addressed in the literature, but many of which are not well delineated or researched. Key gaps and controversies include: (1) Is genetic testing appropriate in symptomatic and asymptomatic individuals without medical actionability? (2) How, if at all, should testing vary based on ethnicity? (3) What are the long-term outcomes of consumer- and research-based genetic testing in presymptomatic PD? (4) What resources are needed for clinical genetic testing, and how is this impacted by models of care and cost-benefit considerations? Addressing these issues will help facilitate the development of consensus and guidelines regarding the approach and access to genetic testing and counseling. This is also needed to guide a multidisciplinary approach that accounts for cultural, geographic, and socioeconomic factors in developing testing guidelines. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A systematic examination of quality-adjusted price index alternatives for medical care using claims data.

We investigate alternative methods for constructing quality-adjusted medical price indexes both theoretically and empirically using medical claims data. The methodology and assumptions applied in the formation of the index have substantive effects on the magnitude of the quality-adjusted price changes. A method based on utility theory produces the most robust and accurate results, while alternative methods used in recent work overstate inflation. Based on Medicare claims data for three medical conditions, we find declining prices across each condition when properly adjusted for quality.

The Association of Social Factors and Time Spent in the NICU for Mothers of Very Preterm Infants.

OBJECTIVES: Evaluate the association between maternal social factors and maternal time spent in the NICU for very preterm infants admitted to 4 level III and IV NICUs. METHODS: In this prospective observational cohort study, we enrolled mother-infant dyads whose infants were born <32 weeks' gestation. Enrollment occurred after 2 weeks of NICU exposure, when maternal social factors and demographic information was collected. Maternal time spent in the NICU was abstracted from the electronic medical record and was dichotomized into 0 to 6 days and ≥6 days per week. Demographic differences between the 2 groups were compared by using χ2 tests. Logistic regression was used to assess the independent association between maternal social factors and the average number of days per week spent in the NICU. RESULTS: A total of 169 mother-infant dyads were analyzed. Maternal social factors associated with more time spent in the NICU included an annual household income of >$100 000, compared with those with an annual household income of <$50 000 (adjusted odds ratio [aOR]: 5.68; 95% confidence interval [CI] 1.77-18.19), a travel time <30 minutes to the NICU (compared with those who traveled >60 minutes [aOR: 7.85; 95% CI 2.81-21.96]), and the lack of other children in the household, compared with women with other children (aOR: 3.15; 95% CI 1.39-7.11). CONCLUSIONS: Maternal time spent in the NICU during a prolonged birth hospitalization of a very preterm infant differed by socioeconomic status, travel time, and presence of other dependents. Strategies to better identify and reduce these disparities to optimize engagement and, subsequently, improve infant health outcomes is needed.

The metabolic profile of Bifidobacterium dentium reflects its status as a human gut commensal.

BACKGROUND: Bifidobacteria are commensal microbes of the mammalian gastrointestinal tract. In this study, we aimed to identify the intestinal colonization mechanisms and key metabolic pathways implemented by Bifidobacterium dentium. RESULTS: B. dentium displayed acid resistance, with high viability over a pH range from 4 to 7; findings that correlated to the expression of Na+/H+ antiporters within the B. dentium genome. B. dentium was found to adhere to human MUC2+ mucus and harbor mucin-binding proteins. Using microbial phenotyping microarrays and fully-defined media, we demonstrated that in the absence of glucose, B. dentium could metabolize a variety of nutrient sources. Many of these nutrient sources were plant-based, suggesting that B. dentium can consume dietary substances. In contrast to other bifidobacteria, B. dentium was largely unable to grow on compounds found in human mucus; a finding that was supported by its glycosyl hydrolase (GH) profile. Of the proteins identified in B. dentium by proteomic analysis, a large cohort of proteins were associated with diverse metabolic pathways, indicating metabolic plasticity which supports colonization of the dynamic gastrointestinal environment. CONCLUSIONS: Taken together, we conclude that B. dentium is well adapted for commensalism in the gastrointestinal tract.

Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut-Brain Axis.

BACKGROUND & AIMS: The human gut microbiota can regulate production of serotonin (5-hydroxytryptamine [5-HT]) from enterochromaffin cells. However, the mechanisms underlying microbial-induced serotonin signaling are not well understood. METHODS: Adult germ-free mice were treated with sterile media, live Bifidobacterium dentium, heat-killed B dentium, or live Bacteroides ovatus. Mouse and human enteroids were used to assess the effects of B dentium metabolites on 5-HT release from enterochromaffin cells. In vitro and in vivo short-chain fatty acids and 5-HT levels were assessed by mass spectrometry. Expression of tryptophan hydroxylase, short-chain fatty acid receptor free fatty acid receptor 2, 5-HT receptors, and the 5-HT re-uptake transporter (serotonin transporter) were assessed by quantitative polymerase chain reaction and immunostaining. RNA in situ hybridization assessed 5-HT-receptor expression in the brain, and 5-HT-receptor-dependent behavior was evaluated using the marble burying test. RESULTS: B dentium mono-associated mice showed increased fecal acetate. This finding corresponded with increased intestinal 5-HT concentrations and increased expression of 5-HT receptors 2a, 4, and serotonin transporter. These effects were absent in B ovatus-treated mice. Application of acetate and B dentium-secreted products stimulated 5-HT release in mouse and human enteroids. In situ hybridization of brain tissue also showed significantly increased hippocampal expression of 5-HT-receptor 2a in B dentium-treated mice relative to germ-free controls. Functionally, B dentium colonization normalized species-typical repetitive and anxiety-like behaviors previously shown to be linked to 5-HT-receptor 2a. CONCLUSIONS: These data suggest that B dentium, and the bacterial metabolite acetate, are capable of regulating key components of the serotonergic system in multiple host tissues, and are associated with a functional change in adult behavior.

The Colorado Hospitals Substance Exposed Newborn Quality Improvement Collaborative: Standardization of Care for Opioid-Exposed Newborns Shortens Length of Stay and Reduces Number of Infants Requiring Opiate Therapy.

OBJECTIVES: To decrease the average length of stay (LOS) of opioid-exposed newborns (OENs) by 20% from baseline from April 2017 to December 2019. METHODS: The Colorado Hospitals Substance Exposed Newborn Quality Improvement Collaborative is a consortium of neonatal providers, public health experts, and legislative experts that provides infrastructure and resources for Colorado birthing hospitals to undertake initiatives focused on improving the care of OENs. The Colorado Hospitals Substance Exposed Newborn Quality Improvement Collaborative was started in September 2017 and includes 19 birthing hospitals in Colorado, with 12 contributing data to the centralized database. The interventions were focused on (1) hospital engagement and (2) increasing nonpharmacologic care (by using the Eat, Sleep, Console assessment tool; developing guidelines for breastfeeding eligibility; employing comfort measures before pharmacologic therapy; and administering opiate therapy on an as-needed basis). RESULTS: From April 2017 to December 2019, 787 OENs were identified. Among infants ≥35 weeks' gestational age without other medical diagnoses (n = 647), statistical process control charts revealed significant reduction in the primary outcome of interest, average hospital LOS, from 14.8 to 5.9 days. For all OENs, receipt of pharmacologic therapy declined from 61% to 23%. Among OENs who received pharmacologic therapy (and were ≥35 weeks' gestational age without other medical diagnoses), average LOS also declined from 21.9 to 8.0 days. CONCLUSIONS: Through standardization of OEN care focused on family engagement and nonpharmacologic care, this statewide collaborative reduced average LOS, the percentage of OENs requiring opiate therapy, and average LOS for OENs requiring opiate therapy.

Enhancing responsiveness of human jejunal enteroids to host and microbial stimuli.

KEY POINTS: Enteroids are a physiologically relevant model to examine the human intestine and its functions. Previously, the measurable cytokine response of human intestinal enteroids has been limited following exposure to host or microbial pro-inflammatory stimuli. Modifications to enteroid culture conditions facilitated robust human cytokine responses to pro-inflammatory stimuli. This new human enteroid culture methodology refines the ability to study microbiome:human intestinal epithelium interactions in the laboratory. ABSTRACT: The intestinal epithelium is the primary interface between the host, the gut microbiome and its external environment. Since the intestinal epithelium contributes to innate immunity as a first line of defence, understanding how the epithelium responds to microbial and host stimuli is an important consideration in promoting homeostasis. Human intestinal enteroids (HIEs) are primary epithelial cell cultures that can provide insights into the biology of the intestinal epithelium and innate immune responses. One potential limitation of using HIEs for innate immune studies is the relative lack of responsiveness to factors that stimulate epithelial cytokine production. We report technical refinements, including removal of extracellular antioxidants, to facilitate enhanced cytokine responses in HIEs. Using this new method, we demonstrate that HIEs have distinct cytokine profiles in response to pro-inflammatory stimuli derived from host and microbial sources. Overall, we found that host-derived cytokines tumour necrosis factor and interleukin-1α stimulated reactive oxygen species and a large repertoire of cytokines. In contrast, microbial lipopolysaccharide, lipoteichoic acid and flagellin stimulated a limited number of cytokines and histamine did not stimulate the release of any cytokines. Importantly, HIE-secreted cytokines were functionally active, as denoted by the ability of human blood-derived neutrophil to migrate towards HIE supernatant containing interleukin-8. These findings establish that the immune responsiveness of HIEs depends on medium composition and stimuli. By refining the experimental culture medium and creating an environment conducive to epithelial cytokine responses by human enteroids, HIEs can facilitate exploration of many experimental questions pertaining to the role of the intestinal epithelium in innate immunity.

Ixazomib for Treatment of Refractory Chronic Graft-versus-Host Disease: A Chronic GVHD Consortium Phase II Trial.

New interventions are needed in advanced chronic graft-versus-host disease (GVHD). In a phase II, single-arm, multicenter trial, we examined the efficacy of ixazomib in patients with chronic GVHD who had progressed after at least 1 previous line of systemic immunosuppressive (IS) therapy. Ixazomib was given as a 4 mg oral dose weekly on days 1, 8, and 15 of a 28-day cycle for up to 6 total cycles. The primary endpoint was 6-month treatment failure, a composite endpoint including death, relapse, and requirement for an additional line of systemic IS therapy. A total of 50 subjects were enrolled at 6 institutions. The median time from the onset of chronic GVHD to enrollment was 2.8 years (interquartile range, 1.5 to 4.3 years). The degree of chronic GVHD at enrollment was National Institutes of Health (NIH)-defined moderate (16%) or severe (84%), predominantly classic (80% versus 20% overlap), with 52% of patients having involvement of 4 or more organs. The patients were heavily pretreated, with 39 (78%) receiving 3 or more previous lines of systemic therapy for chronic GVHD. Of the 50 patients treated, 26 completed 6 months of planned therapy. The 6-month treatment failure rate was significantly lower than the historical benchmark (28% versus 44%; P = .01) previously established in second-line therapy for chronic GVHD. No patient, transplantation, or chronic GVHD variables were significantly associated with 6-month treatment failure. NIH-defined overall response rate was 40% at 6 months. Overall survival was 92% at 6 months and 90% at 12 months. Ixazomib met the primary endpoint of low treatment failure at 6 months in the setting of advanced chronic GVHD. At 6 months, the NIH-defined rate of complete/partial response was 40%, and 52% of patients remained on ixazomib therapy, suggesting that the low treatment failure rate was due in part due to prevention of progressive disease that would have required additional treatment.

Optimizing future planning in Parkinson disease: suggestions for a comprehensive roadmap from patients and care partners.

BACKGROUND: Living with Parkinson disease (PD) is complicated by an unpredictable disease course which can delay planning for future needs. This study explores patient and care partner needs related to future planning using a palliative care framework with physical, psychological, social, cultural, end-of-life, and ethical aspects of care in PD to guide analysis. METHODS: Secondary analysis of patient and care partner interviews from a randomized clinical trial comparing interdisciplinary outpatient palliative care versus standard care for individuals with PD and care partners in an academic setting. Sixty participants were interviewed (30 patients and 30 care partners) about needs related to future planning. Team-based thematic analysis was used to identify key themes. RESULTS: Many care partners and patients living with PD described a desire for information about what to expect and how to plan for the future. Participants posed multiple questions about PD progression and devised the metaphor of a "roadmap" as a guide for decision making and planning. When exploring the concept of a PD roadmap, five themes emerged: (I) desire for a comprehensive tool for future planning, such as a roadmap, (II) care partner preferences for specific future planning, (III) PD-related life changes as opportunity for future planning and decision-making, (IV) cues from family, peers, and medical professionals about "location" on the roadmap, and (V) opportunities and challenges to integrating a PD roadmap into patient-centered care. CONCLUSIONS: Patients and care partners described key needs related to future planning that can inform a comprehensive roadmap to assist with education, communication, and decision making. A roadmap tool can promote individualized anticipatory guidance and multidimensional shared decision-making discussions between patients, care partners, and the healthcare team related to PD progression.

Genetic testing for Parkinson disease: current practice, knowledge, and attitudes among US and Canadian movement disorders specialists.

PURPOSE: Genetic testing for Parkinson disease (PD) has not been widely used in clinical practice. In preparation for upcoming precision medicine-designed clinical trials for GBA and LRRK2, we evaluated movement disorders specialists' current practice, knowledge, attitudes, and barriers to genetic testing in PD. METHODS: An anonymous questionnaire was sent to movement disorders specialists at 146 Parkinson Study Group (PSG) sites in the United States (n = 131) and Canada (n = 15) to assess their knowledge and attitudes about genetic testing for PD. RESULTS: One hundred seventy-eight (47.6%) PSG clinicians completed the questionnaire. Forty-one percent of respondents had not referred any PD patients for genetic testing in the last year and >80% reported referring fewer than 11 patients over the same period. Most common reasons for not referring for genetic testing included lack of insurance coverage/cost to the patient and lack of perceived utility. On a scale of 0-100, the mean level of comfort in respondents' own ability to genetically counsel PD patients on GBA and LRRK2 was 52 (SD = 28). Sixty percent of clinicians correctly answered all questions about the inheritance and penetrance of GBA and LRRK2 variants. CONCLUSIONS: There is an urgent need to increase knowledge and reduce practical barriers to genetic counseling and testing in PD.

Correction: Genetic testing for Parkinson disease: current practice, knowledge, and attitudes among US and Canadian movement disorders specialists.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

ClC transporter activity modulates histidine catabolism in Lactobacillus reuteri by altering intracellular pH and membrane potential.

BACKGROUND: Histamine is a key mediator of the anti-inflammatory activity conferred by the probiotic organism Lactobacillus reuteri ATCC PTA 6475 in animal models of colitis and colorectal cancer. In L. reuteri, histamine synthesis and secretion requires L-histidine decarboxylase and a L-histidine/histamine exchanger. Chloride channel (ClC)-family proton/chloride antiporters have been proposed to act as electrochemical shunts in conjunction with amino acid decarboxylase systems, correcting ion imbalances generated by decarboxylation through fixed ratio exchange of two chloride ions for one proton. This family is unique among transporters by facilitating ion flux in either direction. Here we examine the histidine decarboxylase system in relation to ClC antiporters in the probiotic organism Lactobacillus reuteri. RESULTS: In silico analyses reveal that L. reuteri possesses two ClC transporters, EriC and EriC2, as well as a complete histidine decarboxylase gene cluster (HDC) for the synthesis and export of histamine. When the transport activity of either proton/chloride antiporter is disrupted by genetic manipulation, bacterial histamine output is reduced. Using fluorescent reporter assays, we further show that ClC transporters affect histamine output by altering intracellular pH and membrane potential. ClC transport also alters the expression and activity of two key HDC genes: the histidine decarboxylase (hdcA) and the histidine/histamine exchanger (hdcP). CONCLUSIONS: Histamine production is a potentially beneficial feature for intestinal microbes by promoting long-term colonization and suppression of inflammation and host immune responses. ClC transporters may serve as tunable modulators for histamine production by L. reuteri and other gut microbes.

Environment changes epistasis to alter trade-offs along alternative evolutionary paths.

The fitness effect of a mutation can depend on both its genetic background, known as epistasis, and the prevailing external environment. Many examples of these dependencies are known, but few studies consider both aspects in combination, especially as they affect mutations that have been selected together. We examine interactions between five coevolved mutations in eight diverse environments. We find that mutations are, on average, beneficial across environments, but that there is high variation in their fitness effects, including many examples of mutations conferring a cost in some, but not other, genetic background-environment combinations. Indeed, even when global interaction trends are accounted for, specific local mutation interactions are common and differed across environments. One consequence of this dependence is that the range of trade-offs in genotype fitness across selected and alternative environments are contingent on the particular evolutionary path followed over the mutation landscape. Finally, although specific interactions were common, there was a consistent pattern of diminishing returns epistasis whereby mutation effects were less beneficial when added to genotypes of higher fitness. Our results underline that specific mutation effects are highly dependent on the combination of genetic and external environments, and support a general relationship between a genotype's current fitness and its potential to increase in fitness.

Phagocytosis by macrophages depends on histamine H2 receptor signaling and scavenger receptor 1.

The histamine H2 receptor (H2R) is a G protein-coupled receptor that mediates cyclic AMP production, protein kinase A activation, and MAP kinase signaling. In order to explore the multifaceted effects of histamine signaling on immune cells, phagocytosis was evaluated using primary mouse-derived macrophages. Phagocytosis is initiated by signaling via surface-bound scavenger receptors and can be regulated by autophagy. Absence of H2R signaling resulted in diminished phagocytosis of live bacteria and synthetic microspheres by primary macrophages from histamine H2 receptor gene (Hrh2)-deficient mice. Flow cytometry and immunofluorescence microscopy were used to quantify phagocytosis of phylogenetically diverse bacteria as well as microspheres of defined chemical composition. Autophagy and scavenger receptor gene expression were quantified in macrophages after exposure to Escherichia coli. Expression of the autophagy genes, Becn1 and Atg12, was increased in Hrh2-/- macrophages, indicating upregulation of autophagy pathways. Expression of the Macrophage Scavenger Receptor 1 gene (Msr1) was diminished in Hrh2-deficient macrophages, supporting the possible importance of histamine signaling in scavenger receptor abundance and macrophage function. Flow cytometry confirmed diminished MSR1 surface abundance in Hrh2-/- macrophages. These data suggest that H2R signaling is required for effective phagocytosis by regulating the process of autophagy and scavenger receptor MSR1 abundance in macrophages.

Bifidobacterium dentium Fortifies the Intestinal Mucus Layer via Autophagy and Calcium Signaling Pathways.

Much remains unknown about how the intestinal microbiome interfaces with the protective intestinal mucus layer. Bifidobacterium species colonize the intestinal mucus layer and can modulate mucus production by goblet cells. However, select Bifidobacterium strains can also degrade protective glycans on mucin proteins. We hypothesized that the human-derived species Bifidobacterium dentium would increase intestinal mucus synthesis and expulsion, without extensive degradation of mucin glycans. In silico data revealed that B. dentium lacked the enzymes necessary to extensively degrade mucin glycans. This finding was confirmed by demonstrating that B. dentium could not use naive mucin glycans as primary carbon sources in vitro To examine B. dentium mucus modulation in vivo, Swiss Webster germfree mice were monoassociated with live or heat-killed B. dentium Live B. dentium-monoassociated mice exhibited increased colonic expression of goblet cell markers Krüppel-like factor 4 (Klf4), Trefoil factor 3 (Tff3), Relm-ß, Muc2, and several glycosyltransferases compared to both heat-killed B. dentium and germfree counterparts. Likewise, live B. dentium-monoassociated colon had increased acidic mucin-filled goblet cells, as denoted by Periodic Acid-Schiff-Alcian Blue (PAS-AB) staining and MUC2 immunostaining. In vitro, B. dentium-secreted products, including acetate, were able to increase MUC2 levels in T84 cells. We also identified that B. dentium-secreted products, such as γ-aminobutyric acid (GABA), stimulated autophagy-mediated calcium signaling and MUC2 release. This work illustrates that B. dentium is capable of enhancing the intestinal mucus layer and goblet cell function via upregulation of gene expression and autophagy signaling pathways, with a net increase in mucin production.IMPORTANCE Microbe-host interactions in the intestine occur along the mucus-covered epithelium. In the gastrointestinal tract, mucus is composed of glycan-covered proteins, or mucins, which are secreted by goblet cells to form a protective gel-like structure above the epithelium. Low levels of mucin or alterations in mucin glycans are associated with inflammation and colitis in mice and humans. Although current literature links microbes to the modulation of goblet cells and mucins, the molecular pathways involved are not yet fully understood. Using a combination of gnotobiotic mice and mucus-secreting cell lines, we have identified a human-derived microbe, Bifidobacterium dentium, which adheres to intestinal mucus and secretes metabolites that upregulate the major mucin MUC2 and modulate goblet cell function. Unlike other Bifidobacterium species, B. dentium does not extensively degrade mucin glycans and cannot grow on mucin alone. This work points to the potential of using B. dentium and similar mucin-friendly microbes as therapeutic agents for intestinal disorders with disruptions in the mucus barrier.