Paper Spray Ionization Ion Mobility Mass Spectrometry of Sebum Classifies Biomarker Classes for the Diagnosis of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, and identification of robust biomarkers to complement clinical diagnosis will accelerate treatment options. Here, we demonstrate the use of direct infusion of sebum from skin swabs using paper spray ionization coupled with ion mobility mass spectrometry (PS-IM-MS) to determine the regulation of molecular classes of lipids in sebum that are diagnostic of PD. A PS-IM-MS method for sebum samples that takes 3 min per swab was developed and optimized. The method was applied to skin swabs collected from 150 people and elucidates ∼4200 features from each subject, which were independently analyzed. The data included high molecular weight lipids (>600 Da) that differ significantly in the sebum of people with PD. Putative metabolite annotations of several lipid classes, predominantly triglycerides and larger acyl glycerides, were obtained using accurate mass, tandem mass spectrometry, and collision cross section measurements.

Honey-collecting in prehistoric West Africa from 3500 years ago.

Honey and other bee products were likely a sought-after foodstuff for much of human history, with direct chemical evidence for beeswax identified in prehistoric ceramic vessels from Europe, the Near East and Mediterranean North Africa, from the 7th millennium BC. Historical and ethnographic literature from across Africa suggests bee products, honey and larvae, had considerable importance both as a food source and in the making of honey-based drinks. Here, to investigate this, we carry out lipid residue analysis of 458 prehistoric pottery vessels from the Nok culture, Nigeria, West Africa, an area where early farmers and foragers co-existed. We report complex lipid distributions, comprising n-alkanes, n-alkanoic acids and fatty acyl wax esters, which provide direct chemical evidence of bee product exploitation and processing, likely including honey-collecting, in over one third of lipid-yielding Nok ceramic vessels. These findings highlight the probable importance of honey collecting in an early farming context, around 3500 years ago, in West Africa.

Metabolomics of sebum reveals lipid dysregulation in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder, which is characterised by degeneration of distinct neuronal populations, including dopaminergic neurons of the substantia nigra. Here, we use a metabolomics profiling approach to identify changes to lipids in PD observed in sebum, a non-invasively available biofluid. We used liquid chromatography-mass spectrometry (LC-MS) to analyse 274 samples from participants (80 drug naïve PD, 138 medicated PD and 56 well matched control subjects) and detected metabolites that could predict PD phenotype. Pathway enrichment analysis shows alterations in lipid metabolism related to the carnitine shuttle, sphingolipid metabolism, arachidonic acid metabolism and fatty acid biosynthesis. This study shows sebum can be used to identify potential biomarkers for PD.

Validating Differential Volatilome Profiles in Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that does not currently have a robust clinical diagnostic test. Nonmotor symptoms such as skin disorders have long since been associated with the disease, and more recently a characteristic odor emanating from the skin of people with Parkinson's has been identified. Here, dynamic head space (DHS) thermal desorption (TD) gas chromatography-mass spectrometry (GC-MS) is implemented to directly measure the volatile components of sebum on swabs sampled from people with Parkinson's-both drug naïve and those on PD medications (n = 100) and control subjects (n = 29). Supervised multivariate analyses of data showed 84.4% correct classification of PD cases using all detected volatile compounds. Variable importance in projection (VIP) scores were generated from these data, which revealed eight features with VIP > 1 and p < 0.05 which all presented a downregulation within the control cohorts. Purified standards based on previously annotated analytes of interest eicosane and octadecanal did not match to patient sample data, although multiple metabolite features are annotated with these compounds all with high spectral matches indicating the presence of a series of similar structured species. DHS-TD-GC-MS analysis of a range of lipid standards has revealed the presence of common hydrocarbon species rather than differentiated intact compounds which are hypothesized to be breakdown products of lipids. This replication study validates that a differential volatile profile between control and PD cohorts can be measured using an analytical method that measures volatile compounds directly from skin swabs.

Molecular and isotopic evidence for milk, meat, and plants in prehistoric eastern African herder food systems.

The development of pastoralism transformed human diets and societies in grasslands worldwide. The long-term success of cattle herding in Africa has been sustained by dynamic food systems, consumption of a broad range of primary and secondary livestock products, and the evolution of lactase persistence (LP), which allows digestion of lactose into adulthood and enables the milk-based, high-protein, low-calorie diets characteristic of contemporary pastoralists. Despite the presence of multiple alleles associated with LP in ancient and present-day eastern African populations, the contexts for selection for LP and the long-term development of pastoralist foodways in this region remain unclear. Pastoral Neolithic (c 5000 to 1200 BP) faunas indicate that herders relied on cattle, sheep, and goats and some hunting, but direct information on milk consumption, plant use, and broader culinary patterns is rare. Combined chemical and isotopic analysis of ceramic sherds (n = 125) from Pastoral Neolithic archaeological contexts in Kenya and Tanzania, using compound-specific δ13C and Δ13C values of the major fatty acids, provides chemical evidence for milk, meat, and plant processing by ancient herding societies in eastern Africa. These data provide the earliest direct evidence for milk product consumption and reveal a history of reliance on animal products and other nutrients, likely extracted through soups or stews, and plant foods. They document a 5,000-y temporal framework for eastern Africa pastoralist cuisines and cultural contexts for selection for alleles distinctive of LP in eastern Africa.

Discovery of Volatile Biomarkers of Parkinson's Disease from Sebum.

Parkinson's disease (PD) is a progressive, neurodegenerative disease that presents with significant motor symptoms, for which there is no diagnostic chemical test. We have serendipitously identified a hyperosmic individual, a "Super Smeller" who can detect PD by odor alone, and our early pilot studies have indicated that the odor was present in the sebum from the skin of PD subjects. Here, we have employed an unbiased approach to investigate the volatile metabolites of sebum samples obtained noninvasively from the upper back of 64 participants in total (21 controls and 43 PD subjects). Our results, validated by an independent cohort (n=31), identified a distinct volatiles-associated signature of PD, including altered levels of perillic aldehyde and eicosane, the smell of which was then described as being highly similar to the scent of PD by our "Super Smeller".