US Immigration Westernizes the Human Gut Microbiome.

Many US immigrant populations develop metabolic diseases post immigration, but the causes are not well understood. Although the microbiome plays a role in metabolic disease, there have been no studies measuring the effects of US immigration on the gut microbiome. We collected stool, dietary recalls, and anthropometrics from 514 Hmong and Karen individuals living in Thailand and the United States, including first- and second-generation immigrants and 19 Karen individuals sampled before and after immigration, as well as from 36 US-born European American individuals. Using 16S and deep shotgun metagenomic DNA sequencing, we found that migration from a non-Western country to the United States is associated with immediate loss of gut microbiome diversity and function in which US-associated strains and functions displace native strains and functions. These effects increase with duration of US residence and are compounded by obesity and across generations.

Captivity humanizes the primate microbiome.

The primate gastrointestinal tract is home to trillions of bacteria, whose composition is associated with numerous metabolic, autoimmune, and infectious human diseases. Although there is increasing evidence that modern and Westernized societies are associated with dramatic loss of natural human gut microbiome diversity, the causes and consequences of such loss are challenging to study. Here we use nonhuman primates (NHPs) as a model system for studying the effects of emigration and lifestyle disruption on the human gut microbiome. Using 16S rRNA gene sequencing in two model NHP species, we show that although different primate species have distinctive signature microbiota in the wild, in captivity they lose their native microbes and become colonized with Prevotella and Bacteroides, the dominant genera in the modern human gut microbiome. We confirm that captive individuals from eight other NHP species in a different zoo show the same pattern of convergence, and that semicaptive primates housed in a sanctuary represent an intermediate microbiome state between wild and captive. Using deep shotgun sequencing, chemical dietary analysis, and chloroplast relative abundance, we show that decreasing dietary fiber and plant content are associated with the captive primate microbiome. Finally, in a meta-analysis including published human data, we show that captivity has a parallel effect on the NHP gut microbiome to that of Westernization in humans. These results demonstrate that captivity and lifestyle disruption cause primates to lose native microbiota and converge along an axis toward the modern human microbiome.

Massive blood transfusion following older adult trauma: The effect of blood ratios on mortality.

BACKGROUND: Massive blood transfusion (MBT) following older adult trauma poses unique challenges. Despite extensive evidence on optimal resuscitative strategies in the younger adult patients, there is limited research in the older adult population. METHODS: We used the Trauma Quality Improvement Program (TQIP) database from 2013 to 2017 to identify all patients over 65 years old who received a MBT. We stratified our population into six fresh-frozen plasma:packed red blood cell (FFP:pRBC) ratio cohorts (1:1, 1:2, 1:3, 1:4, 1:5, 1:6+). Our primary outcomes were 24-h and 30-day mortality. We constructed multivariable regression models with 1:1 group as the baseline and adjusted for confounders to estimate the independent effect of blood ratios on mortality. RESULTS: A total of 3134 patients met our inclusion criteria (median age 73 ± 7.6 years, 65% male). On risk-adjusted multivariable analysis, 1:1 FFP:pRBC ratio was independently associated with lowest 24-h mortality (1:2 odds ratio [OR] 1.60, 95% confidence interval [CI] 1.25-2.06, p < 0.001) and 30-day mortality (1:2 OR 1.44, 95% CI 1.15-1.80, p = 0.002). CONCLUSIONS: Compared to all other ratios, the 1:1 FFP:pRBC ratio had the lowest 24-h and 30-day mortality following older adult trauma consistent with findings in the younger adult population.

Gut microbiome signatures of nursing home residents carrying Enterobacteria producing extended-spectrum ß-lactamases.

BACKGROUND: The prevalence of extended beta-lactamase producing Enterobacteriaceae (ESBL-E) has been constantly increasing over the last few decades. These microorganisms that have acquired broad antibiotic resistance are now common human pathogens. Changes in the gut microbiome, induced by antibiotics or other drugs, enable expansion of these microorganisms, but the mechanisms are not yet fully understood. OBJECTIVES: The main objective was to identify specific bacteria and functional pathways and genes characterizing the gut microbiome of nursing home residents carrying ESBL-E, using metagenomics. SUBJECTS AND METHODS: We included 144 residents living in two different nursing homes. All fecal samples were screened for ESBL-E and gut microbiome was characterized using shallow shotgun metagenomic DNA sequencing. RESULTS: Ten nursing home residents were colonized by ESBL-E, namely Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae species, and were compared to non-carriers. We found that ESBL-E carriers had an alteration in within-sample diversity. Using a bootstrap algorithm, we found that the gut microbiome of ESBL-E carriers was depleted in butyrate-producing species, enriched in succinate-producing species and enriched in pathways involved in intracellular pH homeostasis compared to non-carriers individuals. Several energy metabolism pathways were overrepresented in ESBL-E carriers suggesting a greater ability to metabolize multiple microbiota and mucus layer-derived nutrients. CONCLUSIONS: The gut microbiome of ESBL-E carriers in nursing homes harbors specific taxonomic and functional characteristics, conferring an environment that enables Enterobacteriaceae expansion. Here we describe new functional features associated with ESBL-E carriage that could help us to elucidate the complex interactions leading to colonization persistence in the human gut microbiota.

Microbiome Learning Repo (ML Repo): A public repository of microbiome regression and classification tasks.

The use of machine learning in high-dimensional biological applications, such as the human microbiome, has grown exponentially in recent years, but algorithm developers often lack the domain expertise required for interpretation and curation of the heterogeneous microbiome datasets. We present Microbiome Learning Repo (ML Repo, available at https://knights-lab.github.io/MLRepo/), a public, web-based repository of 33 curated classification and regression tasks from 15 published human microbiome datasets. We highlight the use of ML Repo in several use cases to demonstrate its wide application, and we expect it to be an important resource for algorithm developers.

Daily Sampling Reveals Personalized Diet-Microbiome Associations in Humans.

Diet is a key determinant of human gut microbiome variation. However, the fine-scale relationships between daily food choices and human gut microbiome composition remain unexplored. Here, we used multivariate methods to integrate 24-h food records and fecal shotgun metagenomes from 34 healthy human subjects collected daily over 17 days. Microbiome composition depended on multiple days of dietary history and was more strongly associated with food choices than with conventional nutrient profiles, and daily microbial responses to diet were highly personalized. Data from two subjects consuming only meal replacement beverages suggest that a monotonous diet does not induce microbiome stability in humans, and instead, overall dietary diversity associates with microbiome stability. Our work provides key methodological insights for future diet-microbiome studies and suggests that food-based interventions seeking to modulate the gut microbiota may need to be tailored to the individual microbiome. Trial Registration: ClinicalTrials.gov: NCT03610477.

Fecal microbiota transplantation reverses antibiotic and chemotherapy-induced gut dysbiosis in mice.

Fecal microbiota transplantation (FMT) is now widely used to treat recurrent Clostridium difficile infection, but has been less studied as a means to restore microbiome diversity and composition following antibiotic or chemotherapy treatments. The purpose of our study was to assess the efficacy of FMT to reverse antibiotic- and chemotherapy-induced gut dysbiosis in a mouse model. C57BL/6J mice were treated with ampicillin for 1 week and/or received a single intraperitoneal injection of 5-Fluorouracil. Fresh stool was collected and analyzed using shotgun metagenomics and the Illumina sequencing platform. Ampicillin caused a significant and immediate decrease in bacterial species richness and diversity that persisted for one week. In mice that received FMT, disruption of the intestinal microbiota was reversed immediately. Antibiotic and chemotherapy administration caused significant alteration in species distribution, including a decrease in the relative proportions of Clostridium scindens and Faecalibacterium prausnitzii, and an increase in known pathogenic species. In mice receiving FMT, we observed a significant increase in species known to exhibit anti-inflammatory properties. Moreover, chemotherapy led to a critical decrease in key 'health-promoting' species and to an altered functional profile, especially when chemotherapy was administered in tandem with antibiotics, and that FMT can ameliorate these effects.