Pre- and Post-Operative Predictors of Insulin Independence from Total Pancreatectomy and Islet Auto-Transplantation.

OBJECTIVE: This study examined the pre- and post-operative variables that are associated with one-year and long-term insulin independence following total pancreatectomy and islet auto-transplantation (TPIAT). METHODS: Charts of 46 TPIAT patients seen from 2010 to 2022 in a single hospital system were retrospectively analyzed. Pre- and post-operative variables were compared between short- (one year) and long-term (last follow up outside of year one) insulin-independent versus dependent patients. RESULTS: Nine (20%) and seven (15%) patients achieved short- and long-term insulin independence, respectively. The patients were followed for a median of 2.8 years (IQR 1.0, 4.7). Short term insulin-independence was associated with higher median transplanted islet equivalents IEQ/kg (6,981 vs 4,493, p=0.02), lower units of basal insulin on discharge (7 vs 12, p=0.009), and lower rates of discharge from the hospital with an insulin regimen (67% vs 100%, p=0.006). The odds of having short term insulin independence increased by 80% for every 1,000 increase in IEQ/kg (OR 1.80, CI 1.18 to 3.12, p=0.005) and decreased by 32% for every additional basal unit of insulin on discharge (OR 0.68, CI 0.42 to 0.91, p=0.003) on average. Long-term insulin independence was also associated with transplanted IEQ/kg in univariable analysis. No patient on antihyperglycemic medication prior to surgery achieved insulin independence. CONCLUSION: Short- and long-term insulin independence after TPIAT is associated with higher transplanted IEQ/kg and immediate post-operative variables that can be used to inform the discussions clinicians have with their patients regarding glycemic prognosis following TPIAT. Complete insulin independence remains low following TPIAT.

Associations between the Gut Microbiota, Urinary Metabolites, and Diet in Women during the Third Trimester of Pregnancy.

Background: Pregnancy causes many metabolic and physiologic changes. However, associations between gut microbiota, dietary intake, and urinary metabolites are poorly characterized in pregnant women. Objectives: The research objective was to identify dietary and microbial associations with urinary metabolites during pregnancy to elucidate potential biomarkers and microbial targets to improve maternal-fetal health. This is a secondary outcome of the study. Methods: Pregnant women (n = 27) in the Pregnancy EAting and POstpartum Diapers pilot study provided dietary intake information in addition to fecal and urine samples at 36 wk gestation. The gut microbiota was characterized following fecal DNA extraction and 16S rRNA gene sequencing. Urinary metabolites were identified using liquid chromatography high-resolution mass spectrometry. Results: Urinary glycocholate was consistently and negatively correlated with α-carotene intake. There were 9 significant correlations between microbial taxa and urinary metabolites and 13 significant correlations between microbial taxa and dietary intake. On average, Bacteroides were the most abundant taxon in the participants' gut microbiotas. Notably, the gut microbiotas of some pregnant women were not dominated by this taxon. Bacteroides-dominant women consumed more protein, fat, and sodium, and their gut microbiotas had lower alpha diversity than those of nondominant participants. Conclusions: Several urinary metabolites and microbial taxa were associated with maternal diet and gastrointestinal community composition during the third trimester of pregnancy. Future work should determine the mechanisms underlying the associations identified herein.

Fecal Bacterial Communities Differ by Lactation Status in Postpartum Women and Their Infants.

BACKGROUND: Previous research examined effects of human milk on the infant gut microbiota, but little attention has been given to the microbiota of lactating women. RESEARCH AIM: To determine associations between exclusive human milk feeding and gut microbiota characteristics in mothers and infants at 6-weeks postpartum. METHODS: A sample of mother-infant dyads (N = 24) provided fecal samples and questionnaire responses at 6-weeks postpartum as part of the Pregnancy, EAting & POstpartum Diapers study. Deoxyribonucleic acid was extracted from stool samples, followed by (V4) 16S ribosomal ribonucleic acid gene amplicon sequencing. Alpha and beta diversity, in addition to taxa differences, were compared by human milk exposure status, exclusive versus non-exclusive. A subset of dyads (those exclusively fed human milk; n = 14) was analyzed for shared bifidobacterial species using polymerase chain reaction. RESULTS: Alpha diversity was significantly lower in exclusively human milk-fed infants. Maternal lactation status (exclusive vs. partial) and Shannon diversity were associated in univariate analysis but were no longer associated in multivariable regression including body mass index category in the model. Beta diversity (Sorensen dissimilarity) of fecal samples from women and infants was significantly associated with human milk feeding. Of six infants with Bifidobacterium longum subspecies longum in their fecal samples, all their mothers shared the same species. CONCLUSION: Maternal gut microbiotas differ by lactation status, a relationship potentially confounded by body mass index category. Further research is needed to identify whether lactation directly influences the maternal gut microbiota, which may be another mechanism by which lactation influences health.

An Intervention With Michigan-Grown Wheat in Healthy Adult Humans to Determine Effect on Gut Microbiota: Protocol for a Crossover Trial.

BACKGROUND: Daily fiber intake can increase the diversity of the human gut microbiota as well as the abundance of beneficial microbes and their metabolites. Whole-grain wheat is high in fiber. OBJECTIVE: This manuscript presents a study protocol designed to understand the effects of different types of wheat on gastrointestinal tract microbes. METHODS: Human adults will consume crackers made from three types of wheat flour (refined soft white wheat, whole-grain soft white wheat, and whole-grain soft red wheat). In this study, participants will alternate between crackers made from refined soft white wheat flour to those made from whole-grain soft white wheat and whole-grain soft red wheat flour. Survey and stool sample collection will occur after 7-day treatment periods. We will assess how wheat consumption affects gastrointestinal bacteria by sequencing the V4 region of 16S rRNA gene amplicons and the inflammatory state of participants' intestines using enzyme-linked immunosorbent assays. The butyrate production capacity of the gut microbiota will be determined by targeted quantitative real-time polymerase chain reaction. RESULTS: We will report the treatment effects on alpha and beta diversity of the microbiota and taxa-specific differences. Microbiota results will be analyzed using the vegan package in R. Butyrate production capacity and biomarkers of intestinal inflammation will be analyzed using parametric statistical methods such as analysis of variance or linear regression. We expect whole wheat intake to increase butyrate production capacity, bacterial alpha diversity, and abundance of bacterial taxa responsive to phenolic compounds. Soft red wheat is also expected to decrease the concentration of inflammatory biomarkers in the stool of participants. CONCLUSIONS: This protocol describes the methods to be used in a study on the impact of wheat types on the human gastrointestinal microbiota and biomarkers of intestinal inflammation. The analysis of intestinal responses to the consumption of two types of whole wheat will expand our understanding of how specific foods affect health-associated outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29046.

Archive for Research in Child Health (ARCH) and Baby Gut: Study Protocol for a Remote, Prospective, Longitudinal Pregnancy and Birth Cohort to Address Microbiota Development and Child Health.

The infant gut microbiome is shaped by numerous factors such as diet and the maternal microbiota and is also associated with later atopy and obesity. The Archive for Research in Child Health and Baby Gut (ARCHBG) cohort was established in 2015 to (1) understand how the development of the infant gut microbiota is associated with atopy, obesity, and gastrointestinal disease and (2) characterize the associations of maternal pre-pregnancy BMI and infant diet with the development of the gut microbiota. Study participants for ARCHBG are convenience samples recruited through two pipelines in Lansing and Traverse City, Michigan: (1) Archive for Research in Child Health (ARCHGUT) and (2) BABYGUT. A total of (n = 51) mother-infant dyads have been enrolled to date. This prospective cohort study collects maternal pre-pregnancy fecal samples, maternal data, child fecal samples at four timepoints (one week, six months, 12 months, and 24 months), and child data up to five years of age. All samples and data are collected remotely by mail, phone, or drop-off at select locations. Of all participants enrolled, 76.5% (n = 39) of infants have a complete record of stool samples. At least 88.2% (n = 45) of fecal samples were submitted at each timepoint. ARCHBG will allow for a nuanced understanding of the temporal development of the infant gut microbiome and numerous child health outcomes.

The infant gut microbiota at 12 months of age is associated with human milk exposure but not with maternal pre-pregnancy body mass index or infant BMI-for-age z-scores.

BACKGROUND: As obesity rates continue to rise, it is increasingly important to understand factors that can influence body weight and growth, especially from an early age. The infant gut microbiota has broad effects on a variety of bodily processes, but its relation to infant growth is not yet fully characterized. Since the infant gut microbiota is closely related to breastfeeding practices and maternal health, understanding the relationship between these factors and infant growth may provide insight into the origins of childhood obesity. OBJECTIVES: Identify the relationship between human milk exposure, maternal pre-pregnancy body mass index (BMI), the infant gut microbiota, and 12-month-old BMI-for-age z-scores (12M BAZ) to identify key factors that shape infant growth. METHODS: Two Michigan cohorts (ARCHGUT and BABYGUT) comprised of a total of 33 mother-infant dyads provided infant fecal samples at 12M. After DNA extraction, amplification, and sequencing of the V4 16S rRNA region using Illumina MiSeq v2 Chemistry, gut bacterial diversity metrics were analyzed in relation to human milk exposure, maternal pre-pregnancy BMI, and infant growth parameters. RESULTS: Recent human milk exposure was inversely related to maternal pre-pregnancy BMI and most strongly associated with infant gut bacterial community membership and individual gut microbiota richness differences. Maternal pre-pregnancy BMI was not associated with the infant gut microbiota after adjusting for human milk exposure. However, maternal pre-pregnancy BMI was the only factor significantly associated with 12M BAZ. CONCLUSIONS: Human milk exposure is one of the central influences on the infant gut microbiota at 12M of age. However, the lack of association between the infant gut microbiota and 12M-old infant BAZ suggests that genetic, physiological, dietary, and other environmental factors may play a more direct role than the gut microbiota in determining infant BAZ at 12M.

Dietary and plasma carotenoids are positively associated with alpha diversity in the fecal microbiota of pregnant women.

Because microbes use carotenoids as an antioxidant for protection, dietary carotenoids could be associated with gut microbiota composition. We aimed to determine associations among reported carotenoid intake, plasma carotenoid concentrations, and fecal bacterial communities in pregnant women. Pregnant women (n = 27) were enrolled in a two-arm study designed to assess feasibility of biospecimen collection and delivery of a practical nutrition intervention. Plasma and fecal samples were collected and women were surveyed with a 24-hr dietary checklist and recalls. Plasma carotenoids were analyzed by HPLC using photodiode array detection. Fecal bacteria were analyzed by 16S rRNA DNA sequencing. Results presented are cross-sectional from the 36-week gestational study visit combined across both study arms due to lack of significant differences between intervention and usual care groups (n = 23 women with complete data). Recent intake of carotenoid-containing foods included carrots, sweet potatoes, mangos, apricots, and/or bell peppers for 48% of women; oranges/orange juice (17%); egg (39%); tomato/tomato-based sauces (52%); fruits (83%); and vegetables (65%). Average plasma carotenoid concentrations were 6.4 µg/dL α-carotene (AC), 17.7 µg/dL ß-carotene (BC), 11.4 µg/dL cryptoxanthin, 39.0 µg/dL trans-lycopene, and 29.8 µg/dL zeaxanthin and lutein. AC and BC concentrations were higher in women who recently consumed foods high in carotenoids. CR concentrations were higher in women who consumed oranges/orange juice. Microbiota α-diversity positively correlated with AC and BC. Microbiota ß-diversity differed significantly across reported intake of carotenoid containing foods and plasma concentrations of AC. This may reflect an effect of high fiber or improved overall dietary quality, rather than a specific effect of carotenoids. PRACTICAL APPLICATION: Little is known about the association between the gut microbiome and specific dietary microconstituents, such as carotenoids, especially during pregnancy. This research demonstrates that a carotenoid-rich diet during pregnancy supports a diverse microbiota, which could be one mechanism by which carotenoids promote health.

Gut enterotypes are stable during Bifidobacterium and Lactobacillus probiotic supplementation.

The human gut microbiome has been classified into three distinct enterotypes (Bacteroides, Prevotella, and Ruminococcus). The relationship between probiotics and gut enterotype is not yet clear. Cayenne pepper is effective in vitro as a prebiotic for Bifidobacteria and Lactobacilli, so cayenne ingestion with probiotics may lead to more profound gut microbial shifts. We aimed to determine whether probiotics (with or without cayenne pepper) alter gut bacterial community composition and if these changes are associated with the original gut enterotype of the individual. A total of 27 adult participants provided three fecal samples: prior to probiotic treatment (baseline), post probiotic treatment (probiotic), and post probiotic plus cayenne pepper treatment (probiotic + cayenne). DNA was extracted, amplified, and the V4 region sequenced on the Illumina MiSeq platform using V2 chemistry. Sequence reads were processed in mothur and assigned using the SILVA reference by phylotype. Three enterotypes characterized the study population-Bacteroides (B; n = 6), Prevotella (P; n = 11), and Ruminoccocus (R; n = 10). There was no significant increase in probiotic genera in fecal samples after treatment periods. Alpha diversity scores were significantly lower in B-type but not in P- or R-type individuals after probiotic treatment. For the majority of individuals, their enterotype remained constant regardless of probiotic (and cayenne) treatment. This suggests that baseline gut community characteristics and enterotype classification influence responsiveness to probiotic treatment, but that enterotype is stable across administration of prebiotic and probiotics. PRACTICAL APPLICATION: A person's gut microbial community influences their responsiveness to probiotics and prebiotic ingredients. Consumers must understand that it is difficult to shift their gut microbiota even with simultaneous administration of prebiotic and probiotic. Greater understanding of these phenomena will enable consumers to choose the most efficacious products for their needs.