Department of Internal Medicine, Amsterdam University Medical Centers, location VUmc, Amsterdam, The Netherlands.
Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
J Cachexia Sarcopenia Muscle. 2022 Aug;13(4):2188-2201. doi: 10.1002/jcsm.13002. Epub 2022 Jun 14.
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.
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/m if <70 years or BMI < 22 kg/m 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.
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.
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.
老年人尤其容易出现食欲不佳和营养不良。这可能部分归因于肠道微生物群的老化。我们旨在评估社区居住的老年人中肠道微生物群与食欲不佳和营养不良的关系。此外，我们通过将粪便微生物群从队列参与者转移到无菌小鼠中来研究微生物群对体重和身体成分的因果影响。
首先，我们对来自阿姆斯特丹纵向老龄化研究的 358 名荷兰社区居住的健康状况良好的老年人进行了横断面队列研究。数据收集包括身体测量、粪便和血液样本，以及对食欲、饮食摄入和营养状况的广泛问卷调查。通过营养食欲问卷 (CNAQ) 评估食欲，通过低体重指数 (BMI)（70 岁以下 BMI<20kg/m2 或 70 岁以上 BMI<22kg/m2）或过去 2 年内体重减轻>5%来定义营养不良。使用 16S rRNA 测序确定肠道微生物群组成。接下来，我们将来自 12 名有或没有低 BMI 或近期体重减轻的队列参与者的粪便微生物群转移到总共 41 只无菌小鼠中，以研究肠道微生物群对宿主 BMI 和身体成分的潜在因果影响。
我们队列的平均年龄（范围）为 73 岁（65-93 岁）；58.4%为男性。77 名参与者营养不良，21 名参与者食欲不佳（CNAQ<28）。布劳特氏菌属的丰度较低与营养不良相关（log2 倍变化= -0.57，Benjamini-Hochberg 调整后的 P=0.008），而lachnospiraceae、Ruminococcaceae UCG-002、Parabacteroides merdae 和 Dorea formicigenerans 的丰度较高与食欲不佳相关。此外，食欲不佳或营养不良的参与者粪便乙酸盐水平降低（分别为 P=0.006 和 0.026）。最后，接受来自低 BMI 老年人大便微生物群的小鼠在 3 周后体重减轻 1.26g（P=0.086），瘦体重（占体重的百分比，P=0.067）增加 6.13%，而接受来自无低 BMI 或近期体重减轻的老年人大便微生物群的小鼠体重增加 6.13%。
本研究表明肠道微生物群与老年人的食欲不佳和营养不良之间存在多种关联。此外，它首次探索了肠道微生物群与宿主体重和身体成分之间的因果关系。可能，改变微生物群的策略将使易营养不良的老年人受益。
