Weight, habitual fibre intake, and microbiome composition predict tolerance to fructan supplementation.

Fructans are commonly used as dietary fibre supplements for their ability to promote the growth of beneficial gut microbes. However, fructan consumption has been associated with various dosage-dependent side effects. We characterised side effects in an exploratory analysis of a randomised trial in healthy adults (n = 40) who consumed 18 g/day inulin or placebo. We found that individuals weighing more or habitually consuming higher fibre exhibited the best tolerance. Furthermore, we identified associations between gut microbiome composition and host tolerance. Specifically, higher levels of Christensenellaceae R-7 group were associated with gastrointestinal discomfort, and a machine-learning-based approach successfully predicted high levels of flatulence, with [Ruminococcus] torques group and (Oscillospiraceae) UCG-002 sp. identified as key predictive taxa. These data reveal trends that can help guide personalised recommendations for initial inulin dosage. Our results support prior ecological findings indicating that fibre supplementation has the greatest impact on individuals whose baseline fibre intake is lowest.

A Randomized Trial of Inspiratory Training in Children and Adolescents With Obesity.

Introduction: Children with obesity suffer excess dyspnea that contributes to sedentariness. Developing innovative strategies to increase exercise tolerance and participation in children with obesity is a high priority. Because inspiratory training (IT) has reduced dyspnea, we sought to assess IT in children with obesity. Methods: We conducted a 6-week randomized IT trial involving 8- to 17-year-olds with obesity. Participants were randomized 1:1 to either high [75% of maximal inspiratory pressure (MIP)] or low resistance control (15% of MIP) three times weekly. Assessments included adherence, patient satisfaction, and changes in inspiratory strength and endurance, dyspnea scores and total activity level. Results: Among 27 randomized, 24 (89%) completed the intervention. Total session adherence was 72% which did not differ between treatment groups. IT was safe, and more than 90% felt IT benefitted breathing and general health. IT led to a mean improvement (95% CI) in inspiratory strength measured by MIP of 10.0 cm H2O (-3.5, 23.6; paired t-test, p = 0.139) and inspiratory endurance of 8.9 (1.0, 16.8; paired t-test, p = 0.028); however, there was no significant difference between high- and low-treatment groups. IT led to significant reductions in dyspnea with daily activity (p < 0.001) and in prospectively reported dyspnea during exercise (p = 0.024). Among the high- versus low-treatment group, we noted a trend for reduced dyspnea with daily activity (p = 0.071) and increased daily steps (865 vs. -51, p = 0.079). Discussion: IT is safe and feasible for children with obesity and holds promise for reducing dyspnea and improving healthy activity in children with obesity. Breathe-Fit trial NCT05412134.

Interplay between particle size and microbial ecology in the gut microbiome.

Physical particles can serve as critical abiotic factors that structure the ecology of microbial communities. For non-human vertebrate gut microbiomes, fecal particle size (FPS) has been known to be shaped by chewing efficiency and diet. However, little is known about what drives FPS in the human gut. Here, we analyzed FPS by laser diffraction across a total of 76 individuals and found FPS to be strongly individualized. Surprisingly, a behavioral intervention with 41 volunteers designed to increase chewing efficiency did not impact FPS. Dietary patterns could also not be associated with FPS. Instead, we found evidence that mammalian and human gut microbiomes shaped FPS. Fecal samples from germ-free and antibiotic-treated mice exhibited increased FPS relative to colonized mice. In humans, markers of longer transit time were correlated with smaller FPS. Gut microbiota diversity and composition were also associated with FPS. Finally, ex vivo culture experiments using human fecal microbiota from distinct donors showed that differences in microbiota community composition can drive variation in particle size. Together, our results support an ecological model in which the human gut microbiome plays a key role in reducing the size of food particles during digestion, and that the microbiomes of individuals vary in this capacity. These new insights also suggest FPS in humans to be governed by processes beyond those found in other mammals and emphasize the importance of gut microbiota in shaping their own abiotic environment.

Ecological memory of prior nutrient exposure in the human gut microbiome.

Many ecosystems have been shown to retain a memory of past conditions, which in turn affects how they respond to future stimuli. In microbial ecosystems, community disturbance has been associated with lasting impacts on microbiome structure. However, whether microbial communities alter their response to repeated stimulus remains incompletely understood. Using the human gut microbiome as a model, we show that bacterial communities retain an "ecological memory" of past carbohydrate exposures. Memory of the prebiotic inulin was encoded within a day of supplementation among a cohort of human study participants. Using in vitro gut microbial models, we demonstrated that the strength of ecological memory scales with nutrient dose and persists for days. We found evidence that memory is seeded by transcriptional changes among primary degraders of inulin within hours of nutrient exposure, and that subsequent changes in the activity and abundance of these taxa are sufficient to enhance overall community nutrient metabolism. We also observed that ecological memory of one carbohydrate species impacts microbiome response to other carbohydrates, and that an individual's habitual exposure to dietary fiber was associated with their gut microbiome's efficiency at digesting inulin. Together, these findings suggest that the human gut microbiome's metabolic potential reflects dietary exposures over preceding days and changes within hours of exposure to a novel nutrient. The dynamics of this ecological memory also highlight the potential for intra-individual microbiome variation to affect the design and interpretation of interventions involving the gut microbiome.

Improving immunization data quality in Peru and Mexico: Two case studies highlighting challenges and lessons learned.

INTRODUCTION: The Global Vaccine Action Plan and the Regional Immunization Action Plan of the Americas call for countries to improve immunization data quality. Immunization information systems, particularly electronic immunization registries (EIRs), can help to facilitate program management and increase coverage. However, little is known about efforts to develop and implement such systems in low- and middle-income countries. We present the experiences of Mexico and Peru in implementing EIRs. METHODS: We conducted case studies of an EIR in Mexico and of a population registry in Peru. Information was gathered from technical documents, stakeholder focus groups, site visits, and semi-structured interviews of national stakeholders. We organized findings into narratives that emphasized challenges and lessons learned. RESULTS: Mexico built one of the world's first EIRs, incorporating novel features such as local-level tracking of patients; however, insufficient resources and poor data registration practices led to the system's discontinuation. Peru created an information system to improve affiliation to social programs, including the immunization program and quality of demographic data. Mexico's experience highlights lessons in failed sustainability of an EIR and a laudable effort to reform a country's information system. Peru's demonstrates that attempts to improve health and other data may strengthen health systems, including immunization data. Major challenges in information system implementation and sustainability in Peru and Mexico related to funding, clear governance structures, and resistance among health workers. DISCUSSION: These case studies reinforce the need for countries to ensure adequate funding, plans for sustainability, and health worker capacity-building activities before implementing EIRs. They also suggest new approaches to implementation, including economic incentives for sub-national administrative levels and opportunities to link efforts to improve immunization data with other health and political priorities. More information on best practices is needed to ensure the successful adoption and sustainability of immunization registries in low- and middle-income countries.

Detection of vaccine-derived polioviruses in Mexico using environmental surveillance.

BACKGROUND: Early detection and control of vaccine-derived poliovirus (VDPV) emergences are essential to secure the gains of polio eradication. METHODS: Serial sewage samples were collected in 4 towns of Mexico before, throughout, and after the May 2010 oral poliovirus vaccine (OPV) mass immunization campaign. Isolation and molecular analysis of polioviruses from sewage specimens monitored the duration of vaccine-related strains in the environment and emergence of vaccine-derived polioviruses in a population partially immunized with inactivated poliovirus vaccine (IPV). RESULTS: Sabin strains were identified up to 5-8 weeks after the campaign in all towns; in Aguascalientes, 1 Sabin 3 was isolated 16 weeks after the campaign, following 7 weeks with no Sabin strains detected. In Tuxtla Gutiérrez, type 2 VDPV was isolated from 4 samples collected before and during the campaign, and type 1 VDPV from 1 sample collected 19 weeks afterward. During 2009-2010, coverage in 4 OPV campaigns conducted averaged only 57% and surveillance for acute flaccid paralysis (AFP) was suboptimal (AFP rate<1 per 100,000 population<15 years of age) in Tuxtla Gutierrez. CONCLUSIONS: VDPVs may emerge and spread in settings with inadequate coverage with IPV/OPV vaccination. Environmental surveillance can facilitate early detection in these settings.

Adequacy of surveillance to detect endemic rubella transmission in the United States.

BACKGROUND: Reported rubella cases in the United States are at the lowest numbers since the introduction of vaccine, suggesting that endemic transmission may have been interrupted. It is necessary to validate that the observed absence of rubella is due to the disappearance of disease rather than a failure of rubella surveillance. METHODS: Adequate rubella surveillance to detect ongoing transmission is characterized by evidence that rubella investigations are being conducted, detection of importations, and lack of spread from confirmed cases. We reviewed rubella surveillance data and activities from 5 sources: (1) data reported to the national surveillance system; (2) a survey of health departments and public health laboratories, including questions regarding any links between measles and rubella surveillance; (3) enhanced rubella surveillance activities in California and in New York City; (4) sentinel surveillance along the US-Mexico border; and (5) case detection in 8 large health maintenance organizations (HMOs). RESULTS: During 2002-2004, 35 cases of rubella were reported to the national system, including 12 (34%) imported cases. The 39 programs that responded to our survey reported conducting 1482 investigations for rubella; according to another national survey, 1921 investigations were conducted for measles. Forty-one laboratories responded to our survey and reported conducting 6428 tests for acute rubella. No previously undetected (or unreported) cases of rubella or congenital rubella syndrome were identified by our survey or reviews of surveillance in California, New York, and along the US-Mexico border, and no additional cases were detected in the HMO database. CONCLUSIONS: No previously unrecognized spread cases or outbreaks of rubella were detected. Surveillance in the United States is sufficiently sensitive to identify indigenous cases of rubella, if they were occurring, supporting the contention that rubella has been eliminated from the United States.

Identical genotype B3 sequences from measles patients in 4 countries, 2005.

Surveillance of measles virus detected an epidemiologic link between a refugee from Kenya and a Dutch tourist in New Jersey, USA. Identical genotype B3 sequences from patients with contemporaneous cases in the United States, Canada, and Mexico in November and December 2005 indicate that Kenya was likely to have been the common source of virus.