IHU-Méditerranée Infection, Marseille, France.
Aix Marseille Univ, IRD, AP-HM, MEPHI, Marseille, France.
PLoS Negl Trop Dis. 2021 Jun 29;15(6):e0009555. doi: 10.1371/journal.pntd.0009555. eCollection 2021 Jun.
Severe acute malnutrition (SAM) is a major public health problem affecting children under the age of five in many low- and middle-income countries, and its resolution would contribute towards achieving the several sustainable development goals. The etiology of SAM is pluri-factorial, including delayed maturation of the gut microbiota, suboptimal feeding practices and dysfunctional breastfeeding. The recent serendipitous detection of Listeria monocytogenes in the breast milk of Malian women, in contrast to French women, suggests a possible association with SAM.
METHODOLOGY/ PRINCIPAL FINDINGS: To investigate the possible association of L. monocytogenes carriage in breast milk and SAM, a case-control study was performed in Senegal, with subjects recruited from two areas. Using 16S amplicon sequencing, a culture independent method, 100% (152/152) of the mothers were positive for L. monocytogenes in their breast milk while qPCR analysis gave lower recovery rates. Interestingly, after enrichment in Fraser broth and seeding on PALCALM agar, all 10 isolated strains were isolated from the milk of 10 mothers who had SAM children which also had a significantly increased relative abundance of L. monocytogenes (0.34 (SD 0.35) vs 0.05 (SD 0.07) in controls, p<0.0001). The high genomic similarity between these strains and Malian breast milk strains from a previous study supports the hypothesis of endemic clone carriage in West Africa. Moreover, the in vitro growth inhibition of L. monocytogenes using breast milk samples was obtained from only 50% of the milk of mothers who had SAM children, in contrast to control samples which systematically inhibited the growth of L. monocytogenes with a higher inhibition diameter (15.7 mm (SD 2.3) in controls versus 3.5 mm (SD 4.6) in SAM, p = 0.0001). Lactobacillus and Streptococcus isolated from the breast milk of controls inhibit L. monocytogenes in a species-dependent manner.
CONCLUSIONS/SIGNIFICANCE: Our study reveals a previously unsuspected carriage of L. monocytogenes in the breast milk of West African women, which is associated with SAM. The inhibitory effect of human selected lactic acid bacterial species against L. monocytogenes might provide new therapeutic and inexpensive options to prevent and treat this neglected public health issue.
严重急性营养不良(SAM)是许多中低收入国家 5 岁以下儿童面临的一个主要公共卫生问题,解决这一问题将有助于实现几个可持续发展目标。SAM 的病因是多因素的,包括肠道微生物群成熟延迟、喂养方式不佳和母乳喂养功能障碍。最近在马里妇女的母乳中意外检测到李斯特菌,而在法国妇女的母乳中则没有,这表明两者之间可能存在关联。
方法/主要发现:为了研究母乳中李斯特菌携带与 SAM 之间可能存在的关联,在塞内加尔进行了一项病例对照研究,研究对象来自两个地区。使用 16S 扩增子测序这一非培养方法,100%(152/152)的母亲的母乳中携带李斯特菌,而 qPCR 分析的回收率较低。有趣的是,在富氏肉汤中富集并在 PALCALM 琼脂上接种后,从 10 位患有 SAM 儿童的母亲的牛奶中分离出了所有 10 株分离株,这些母亲的母乳中李斯特菌的相对丰度显著增加(0.34(SD 0.35)与对照相比为 0.05(SD 0.07),p<0.0001)。这些菌株与之前研究中来自马里母乳的菌株之间的高基因组相似性支持了西非地方性携带克隆的假说。此外,仅从 50%患有 SAM 儿童的母亲的母乳中获得了抑制李斯特菌生长的体外实验结果,而对照样本则以更高的抑制直径(对照为 15.7 毫米(SD 2.3),SAM 为 3.5 毫米(SD 4.6),p = 0.0001)系统地抑制了李斯特菌的生长。从对照母乳中分离出的乳酸杆菌和链球菌以物种依赖的方式抑制李斯特菌。
结论/意义:本研究揭示了西非妇女母乳中携带李斯特菌的先前未被怀疑的情况,这与 SAM 有关。人类选择的乳酸细菌物种对李斯特菌的抑制作用可能为预防和治疗这一被忽视的公共卫生问题提供新的治疗和廉价选择。