Wong Jeremy P H, Chillier Noémie, Fischer-Stettler Michaela, Zeeman Samuel C, Battin Tom J, Persat Alexandre
Institute of Bioengineering and Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
School of Architecture, Civil and Environmental Engineering, École Polytechnique Fédérale de Lausanne, Sion, Switzerland.
mBio. 2024 Mar 13;15(3):e0259923. doi: 10.1128/mbio.02599-23. Epub 2024 Feb 20.
The human colon hosts hundreds of commensal bacterial species, many of which ferment complex dietary carbohydrates. To transform these fibers into metabolically accessible compounds, microbes often express a series of dedicated enzymes homologous to the starch utilization system (Sus) encoded in polysaccharide utilization loci (PULs). The genome of (), a common member of the human gut microbiota, encodes nearly 100 PULs, conferring a strong metabolic versatility. While the structures and functions of individual enzymes within the PULs have been investigated, little is known about how polysaccharide complexity impacts the function of Sus-like systems. We here show that the activity of Sus-like systems depends on polysaccharide size, ultimately impacting bacterial growth. We demonstrate the effect of size-dependent metabolism in the context of dextran metabolism driven by the specific utilization system PUL48. We find that as the molecular weight of dextran increases, growth rate decreases and lag time increases. At the enzymatic level, the dextranase BT3087, a glycoside hydrolase (GH) belonging to the GH family 66, is the main GH for dextran utilization, and BT3087 and BT3088 contribute to dextran metabolism in a size-dependent manner. Finally, we show that the polysaccharide size-dependent metabolism of impacts its metabolic output in a way that modulates the composition of a producer-consumer community it forms with . Altogether, our results expose an overlooked aspect of metabolism that can impact the composition and diversity of microbiota.
Polysaccharides are complex molecules that are commonly found in our diet. While humans lack the ability to degrade many polysaccharides, their intestinal microbiota contain bacterial commensals that are versatile polysaccharide utilizers. The gut commensal dedicates roughly 20% of their genomes to the expression of polysaccharide utilization loci for the broad range utilization of polysaccharides. Although it is known that different polysaccharide utilization loci are dedicated to the degradation of specific polysaccharides with unique glycosidic linkages and monosaccharide compositions, it is often overlooked that specific polysaccharides may also exist in various molecular weights. These different physical attributes may impact their processability by starch utilization system-like systems, leading to differing growth rates and nutrient-sharing properties at the community level. Therefore, understanding how molecular weight impacts utilization by gut microbe may lead to the potential design of novel precision prebiotics.
人类结肠中栖息着数百种共生细菌，其中许多细菌可发酵复杂的膳食碳水化合物。为了将这些纤维转化为可代谢利用的化合物，微生物通常会表达一系列与多糖利用位点（PULs）中编码的淀粉利用系统（Sus）同源的专用酶。人肠道微生物群的常见成员（）的基因组编码近100个PULs，赋予其强大的代谢多功能性。虽然已经对PULs中个别酶的结构和功能进行了研究，但对于多糖的复杂性如何影响类Sus系统的功能却知之甚少。我们在此表明，类Sus系统的活性取决于多糖的大小，最终影响细菌的生长。我们在由特定利用系统PUL48驱动的葡聚糖代谢背景下证明了大小依赖性代谢的影响。我们发现，随着葡聚糖分子量的增加，（）的生长速率降低，延迟期延长。在酶水平上，葡聚糖酶BT3087是一种属于糖苷水解酶家族66的糖苷水解酶（GH），是利用葡聚糖的主要GH，并且BT3087和BT3088以大小依赖的方式促进（）的葡聚糖代谢。最后，我们表明（）的多糖大小依赖性代谢以一种调节其与（）形成的生产者 - 消费者群落组成的方式影响其代谢输出。总之，我们的结果揭示了（）代谢中一个被忽视的方面，它可能影响微生物群的组成和多样性。
多糖是我们饮食中常见的复杂分子。虽然人类缺乏降解许多多糖的能力，但他们肠道中的微生物群包含能够广泛利用多糖的共生细菌。肠道共生菌（）将其大约20%的基因组用于表达多糖利用位点，以广泛利用多糖。虽然已知不同的多糖利用位点专门用于降解具有独特糖苷键和单糖组成的特定多糖，但人们常常忽略特定多糖也可能以各种分子量存在。这些不同的物理属性可能会影响它们被类淀粉利用系统加工的过程，从而在群落水平上导致不同的生长速率和营养共享特性。因此，了解分子量如何影响肠道微生物的利用可能会导致新型精准益生元的潜在设计。
