Gut microbial characteristics in poor appetite and undernutrition: a cohort of older adults and microbiota transfer in germ-free mice

Kristina S. Fluitman, Mark Davids, Louise E. Olofsson, Madelief Wijdeveld, Valentina Tremaroli, Bart J.F. Keijser, Marjolein Visser, Fredrik Bäckhed, Max Nieuwdorp, Richard G. IJzerman*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Background: Older adults are particularly prone to the development of poor appetite and undernutrition. Possibly, this is partly due to the aged gut microbiota. We aimed to evaluate the gut microbiota in relation to both poor appetite and undernutrition in community-dwelling older adults. Furthermore, we studied the causal effects of the microbiota on body weight and body composition by transferring faecal microbiota from cohort participants into germ-free mice. Methods: First, we conducted a cross-sectional cohort study of 358 well-phenotyped Dutch community-dwelling older adults from the Longitudinal Aging Study Amsterdam. Data collection included body measurements, a faecal and blood sample, as well as extensive questionnaires on appetite, dietary intake, and nutritional status. Appetite was assessed by the Council of Nutrition Appetite Questionnaire (CNAQ) and undernutrition was defined by either a low body mass index (BMI) (BMI < 20 kg/m2 if <70 years or BMI < 22 kg/m2 if ≥70 years) or >5% body weight loss averaged over the last 2 years. Gut microbiota composition was determined with 16S rRNA sequencing. Next, we transferred faecal microbiota from 12 cohort participants with and without low BMI or recent weight loss into a total of 41 germ-free mice to study the potential causal effects of the gut microbiota on host BMI and body composition. Results: The mean age (range) of our cohort was 73 (65–93); 58.4% was male. Seventy-seven participants were undernourished and 21 participants had poor appetite (CNAQ < 28). A lower abundance of the genus Blautia was associated with undernutrition (log2 fold change = −0.57, Benjamini–Hochberg-adjusted P = 0.008), whereas higher abundances of taxa from Lachnospiraceae, Ruminococcaceae UCG-002, Parabacteroides merdae, and Dorea formicigenerans were associated with poor appetite. Furthermore, participants with poor appetite or undernutrition had reduced levels of faecal acetate (P = 0.006 and 0.026, respectively). Finally, there was a trend for the mice that received faecal microbiota from older adults with low BMI to weigh 1.26 g less after 3 weeks (P = 0.086) and have 6.13% more lean mass (in % body weight, P = 0.067) than the mice that received faecal microbiota from older adults without low BMI or recent weight loss. Conclusions: This study demonstrates several associations of the gut microbiota with both poor appetite and undernutrition in older adults. Moreover, it is the first to explore a causal relation between the aged gut microbiota and body weight and body composition in the host. Possibly, microbiota-manipulating strategies will benefit older adults prone to undernutrition.

Original languageEnglish
Pages (from-to)2188-2201
Number of pages14
JournalJournal of Cachexia, Sarcopenia and Muscle
Volume13
Issue number4
Early online date14 Jun 2022
DOIs
Publication statusPublished - Aug 2022

Bibliographical note

Funding Information:
This study was supported by the European Union Horizon 2020 PROMISS project ‘PRevention Of Malnutrition In Senior Subjects in the EU’ (grant agreement no. 678732). The content only reflects the author's view and the Commission is not responsible for any use that may be made of the information it contains. The Longitudinal Aging Study Amsterdam is supported by a grant from the Netherlands Ministry of Health Welfare and Sports, Directorate of Long‐Term Care. The LASA data collection in 2012–13 was financially supported by the Netherlands Organization for Scientific Research (NWO) in the framework of the project ‘New Cohorts of young old in the 21st century’ (file number 480‐10‐014). M.N. is supported by a personal ZONMW VIDI grant 2013 (016.146.327), a personal ZONMW VICI grant 2020 (09150182010020), and a Dutch Heart Foundation CVON IN CONTROL Young Talent Grant 2013. F.B. and M.N. are supported by a Transatlantic Networks of Excellence Award from the Leducq Foundation (17CVD01) and from JPI A Healthy Diet for a Healthy Life (2017‐01996_3).

Publisher Copyright:
© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.

Funding

This study was supported by the European Union Horizon 2020 PROMISS project ‘PRevention Of Malnutrition In Senior Subjects in the EU’ (grant agreement no. 678732). The content only reflects the author's view and the Commission is not responsible for any use that may be made of the information it contains. The Longitudinal Aging Study Amsterdam is supported by a grant from the Netherlands Ministry of Health Welfare and Sports, Directorate of Long‐Term Care. The LASA data collection in 2012–13 was financially supported by the Netherlands Organization for Scientific Research (NWO) in the framework of the project ‘New Cohorts of young old in the 21st century’ (file number 480‐10‐014). M.N. is supported by a personal ZONMW VIDI grant 2013 (016.146.327), a personal ZONMW VICI grant 2020 (09150182010020), and a Dutch Heart Foundation CVON IN CONTROL Young Talent Grant 2013. F.B. and M.N. are supported by a Transatlantic Networks of Excellence Award from the Leducq Foundation (17CVD01) and from JPI A Healthy Diet for a Healthy Life (2017‐01996_3).

FundersFunder number
Dutch Heart Foundation CVON IN CONTROL
Netherlands Ministry of Health Welfare and Sports, Directorate of Long-Term Care
Netherlands Ministry of Health Welfare and Sports, Directorate of Long‐Term Care
European Commission678732
Fondation Leducq2017‐01996_3, 17CVD01
Nederlandse Organisatie voor Wetenschappelijk Onderzoek09150182010020, 016.146.327, 480‐10‐014
Horizon 2020

    Keywords

    • Appetite
    • Germ-free mice
    • Gut microbiota
    • Microbiota transfer experiment
    • Older adults
    • Undernutrition

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